tbuckley/cabot-search huggingface dataset:
Differential Crizotinib Response Duration Among <i>ALK</i> Fusion Variants in <i>ALK</i>-Positive Non–Small-Cell Lung Cancer
Authors: Tatsuya Yoshida, Yuko Oya, Kosuke Tanaka, Junichi Shimizu, Yoshitsugu Horio, Hiroaki Kuroda, Yukinori Sakao, Toyoaki Hida, Yasushi Yatabe
Journal: Journal of Clinical Oncology (2016)

Anaplastic lymphoma kinase (ALK) rearrangement-positive non-small-cell lung cancers can be effectively treated with an ALK tyrosine kinase inhibitor (TKI) such as crizotinib, but the response magnitude and duration are heterogeneous. Several ALK variants have been identified, but few studies have focused on the effects of different ALK variants on the efficacy of crizotinib.Among 55 patients treated with crizotinib as the initial ALK-TKI between January 2007 and December 2014, we identified 35 patients with tumor specimens that could be evaluated for ALK variants by reverse transcription polymerase chain reaction. We retrospectively evaluated the efficacy of crizotinib on the basis of the objective response rate and progression-free survival (PFS) according to the ALK variants.The most frequent ALK variant was variant 1 in 19 patients (54%), followed by variant 2 in five patients (14%), variant 3a/3b in four patients (12%), and other variants in seven patients (20%). Objective response rate was 69% in all patients, whereas it was 74% and 63% in the variant 1 and non-variant 1 groups, respectively. The median PFS time was significantly longer in patients with variant 1 than in those with non-variant 1 (median PFS, 11.0 months [95% CI, 6.5 to 43.0 months] v 4.2 months [95% CI, 1.6 to 10.2 months], respectively; P < .05). Multivariable analysis identified two significant factors associated with PFS duration, ALK variant 1 (hazard ratio, 0.350; 95% CI, 0.128 to 0.929; P < .05) and advanced stage (hazard ratio, 4.646; 95% CI, 1.381 to 21.750; P < .05).Our results indicate the better efficacy of crizotinib in patients with ALK variant 1 versus non-variant 1. The ALK variant status might affect the efficacy of ALK-TKIs.
ELTD1, an effective anti-angiogenic target for gliomas: preclinical assessment in mouse GL261 and human G55 xenograft glioma models
Authors: Jadith Ziegler, Richard Pody, Patricia Coutinho de Souza, Blake Evans, Debra Saunders, Nataliya Smith, Samantha Mallory, Charity Njoku, Yunzhou Dong, Hong Chen, Jiali Dong, Megan Lerner, Osamah Mian, Sai Tummala, James Battiste, Kar-Ming Fung, Jonathan D. Wren, Rheal A. Towner
Journal: Neuro-Oncology (2016)

Despite current therapies, glioblastoma is a devastating cancer, and validation of effective biomarkers for it will enable better diagnosis and therapeutic intervention for this disease. We recently discovered a new biomarker for high-grade gliomas, ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1) via bioinformatics, and validated that ELTD1 protein levels are significantly higher in human and rodent gliomas. The focus of this study was to assess the effect on tumor growth of an antibody against ELTD1 in orthotopic, GL261, and G55 xenograft glioma models.The effect of anti-ELTD1 antibody therapy was assessed by animal survival, MRI measured tumor volumes, MR angiography, MR perfusion imaging, and immunohistochemistry (IHC) characterization of microvessel density in mouse glioma models. Comparative treatments included anti-vascular endothelial growth factor (VEGF) and anti-c-Met antibody therapies, compared with untreated controls.Tumor volume and survival data in this study show that antibodies against ELTD1 inhibit glioma growth just as effectively or even more so compared with other therapeutic targets studied, including anti-VEGF antibody therapy. Untreated GL261 or G55 tumors were found to have significantly higher ELTD1 levels (IHC) compared with contralateral normal brain. The anti-angiogenic effect of ELTD1 antibody therapy was observed in assessment of microvessel density, as well as from MR angiography and perfusion measurements, which indicated that anti-ELTD1 antibody therapy significantly decreased vascularization compared with untreated controls.Either as a single therapy or in conjunction with other therapeutic approaches, anti-ELTD1 antibodies could be a valuable new clinical anti-angiogenic therapeutic for high-grade gliomas.
Models of a heroin epidemic
Authors: D J Egan, D O Robinson
Journal: American Journal of Psychiatry (1979)

Heroin addiction may be considered an epidemic disease that is communicated by people who are addicted to the drug. It has been suggested that the most recent epidemic in the United States had its peak incidence in 1969. The age of heroin addicts entering treatment has increased systematically from 1973 to 1976 at a rate of less than one year of age per calendar year. This pattern is consistent with a moderate decline in a national heroin epidemic or a geographical migration of the epidemic from more to less populated areas. There are also seasonal trends in the age of admission to treatment.
Pre-Transplant C-Reactive Protein (CRP), Ferritin and Albumin As Biomarkers to Predict Transplant Related Mortality (TRM) after Allogeneic Hematopoietic Cell Transplant (HCT)
Authors: Andrew S. Artz, Brent R. Logan, Xiaochun Zhu, Görgün Akpek, Rodrigo Martino, Vikas Gupta, Hillard M. Lazarus, Mark R. Litzow, Alison Wakoff Loren, Navneet S. Majhail, Richard T. Maziarz, Philip L. McCarthy, Uday R. Popat, Wael Saber, Stephen R. Spellman, Olle Ringdén, Kenneth R. Cooke, Marcelo C. Pasquini
Journal: Blood (2014)
Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient
Authors: Markus W. Löffler, P. Anoop Chandran, Karoline Laske, Christopher Schroeder, Irina Bonzheim, Mathias Walzer, Franz J. Hilke, Nico Trautwein, Daniel J. Kowalewski, Heiko Schuster, Marc Günder, Viviana A. Carcamo Yañez, Christopher Mohr, Marc Sturm, Huu-Phuc Nguyen, Olaf Riess, Peter Bauer, Sven Nahnsen, Silvio Nadalin, Derek Zieker, Jörg Glatzle, Karolin Thiel, Nicole Schneiderhan-Marra, Stephan Clasen, Hans Bösmüller, Falko Fend, Oliver Kohlbacher, Cécile Gouttefangeas, Stefan Stevanović, Alfred Königsrainer, Hans-Georg Rammensee
Journal: Journal of Hepatology (2016)

We report a novel experimental immunotherapeutic approach in a patient with metastatic intrahepatic cholangiocarcinoma. In the 5year course of the disease, the initial tumor mass, two local recurrences and a lung metastasis were surgically removed. Lacking alternative treatment options, aiming at the induction of anti-tumor T cells responses, we initiated a personalized multi-peptide vaccination, based on in-depth analysis of tumor antigens (immunopeptidome) and sequencing.Tumors were characterized by immunohistochemistry, next-generation sequencing and mass spectrometry of HLA ligands.Although several tumor-specific neo-epitopes were predicted in silico, none could be validated by mass spectrometry. Instead, a personalized multi-peptide vaccine containing non-mutated tumor-associated epitopes was designed and applied. Immunomonitoring showed vaccine-induced T cell responses to three out of seven peptides administered. The pulmonary metastasis resected after start of vaccination showed strong immune cell infiltration and perforin positivity, in contrast to the previous lesions. The patient remains clinically healthy, without any radiologically detectable tumors since March 2013 and the vaccination is continued.This remarkable clinical course encourages formal clinical studies on adjuvant personalized peptide vaccination in cholangiocarcinoma.Metastatic cholangiocarcinomas, cancers that originate from the liver bile ducts, have very limited treatment options and a fatal prognosis. We describe a novel therapeutic approach in such a patient using a personalized multi-peptide vaccine. This vaccine, developed based on the characterization of the patient's tumor, evoked detectable anti-tumor immune responses, associating with long-term tumor-free survival.
Tuberculous Salpingitis. A Clinical Study of 200 Cases.
Authors: G BERGGREN
Journal: JAMA (1921)

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
Exploring providers and survivors perceptions of dedicated cancer survivorship care clinics.
Authors: Guadalupe R. Palos, Richard W Wagner, Megan Hebdon, Sara McComb, Katherine Ramsey Gilmore, Patricia Chapman, Maria Alma Rodriguez
Journal: Journal of Clinical Oncology (2016)

117 Background: The complex physical and psychological sequelae faced by cancer survivors require methodical follow-up care. A growing body of evidence suggests clinics and providers dedicated to survivorship care is a promising approach for addressing these needs. Yet there is limited published data of survivors and providers' perceptions of dedicated survivorship care. This study’s objective was to ascertain the strengths and weaknesses of clinical services provided in survivorship clinics. Methods: This study used a mixed-methods approach with stratified purposive sampling in the breast, genitourinary, and head/neck survivorship clinics. Characteristics used for stratification included: disease site, staffing characteristics, and clinical infrastructure. Semi-structured interviews were conducted with survivors and stakeholders, i.e. providers and executive leaders. Staff trained in qualitative methods conducted the interviews. Standardized questions focused on: 1) overall impression of the experience, 2) perceptions of the survivorship care plan (SCP), and 3) recommendations for improving clinical services. A brief survey collected demographic and clinical data. De-identified interviews were audio-recorded, transcribed verbatim, and analyzed to confirm themes. Descriptive statistics were used to summarize all data. Results: A total of 52 participants (36 survivors and 16 stakeholders) were interviewed. Overlapping themes centered on value, continuity of care, and uncertainty about SCPs. Survivors often reported not being able to remember any details of the SCP. Providers felt “patients really like coming here…it’s not as stressful” while survivors reported finding value in receiving “coaching for having a better lifestyle”. Both groups discussed resistance to the survivorship transition process, particularly providers as illustrated in a statement that “they [survivors] are the best part of their day. Conclusions: Dedicated survivorship clinics were perceived as being valuable by both providers and survivors, despite challenges associated with services. Our findings suggest further work is warranted to better understand the nuances of survivorship care and clinics.
The Impact Of Balanced and Unbalanced Karyotypes On Prognosis Of CML: From Chronic Phase To Blast Crisis
Authors: Lida Kalmanti, Christian Dietz, Claudia Haferlach, Gudrun Göring, Brigitte Schlegelberger, Martine Jotterand, Rüdiger Hehlmann, Andreas Hochhaus, Martin C. Müller, Benjamin Hanfstein, Ulrike Proetel, Stefan W. Krause, Hermann Einsele, Jolanta Dengler, Christiane Falge, Lothar Kanz, Andreas Neubauer, Michael Kneba, Frank Stegelmann, Michael Pfreundschuh, Cornelius F. Waller, Karsten Spiekermann, Michael Lauseker, Markus Pfirrmann, Joerg Hasford, Wolf-Karsten Hofmann, Susanne Saussele, Alice Fabarius
Journal: Blood (2013)
Reexamining the Efficacy and Value of Percutaneous Coronary Intervention for Patients With Stable Ischemic Heart Disease
Authors: William S. Weintraub, William E. Boden
Journal: JAMA Internal Medicine (2016)

Percutaneous coronary intervention (PCI) continues to be performed frequently for patients with stable ischemic heart disease, despite uncertain efficacy. Individual randomized trial data and meta-analyses have not demonstrated that PCI in addition to optimal medical therapy reduces the incidence of death or myocardial infarction in patients with stable disease. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial did not show benefit for cardiovascular outcomes or mortality but did find a modest improvement in quality of life that did not persist at 3 years. Long-term follow-up from COURAGE (up to 15 years) found no differences in mortality, consistent with other published literature. How PCI could reduce long-term mortality or prevent myocardial infarction is not clear because sites of future plaque rupture leading to myocardial infarction are unpredictable and PCI can only treat localized anatomic segments of obstructive atherosclerosis. In addition, PCI is expensive, and the value to society of PCI for stable disease has not been demonstrated. The ISCHEMIA trial will assess the role of PCI for stable ischemic heart disease using newer technology and in patients with greater ischemic burden than in COURAGE. After nearly a decade, the COURAGE trial and other studies have given us pause to critically reexamine the role of PCI for patients with stable ischemic heart disease. Until further research can show that PCI can reduce cardiovascular events in these patients, a first-line strategy of optimal medical therapy is known to be safe, effective, and noninferior to PCI, and our practice should more closely follow this strategy.
Lung–Kidney Cross-Talk in the Critically Ill Patient
Authors: Faeq Husain-Syed, Arthur S. Slutsky, Claudio Ronco
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Discoveries have emerged highlighting the complex nature of the interorgan cross-talk between the kidney and the lung. Vascular rigidity, neurohormonal activation, tissue hypoxia, and abnormal immune cell signaling have been identified as common pathways leading to the development and progression of chronic kidney disease. However, our understanding of the causal relationships between lung injury and kidney injury is not precise. This review discusses a number of features and mechanisms of renal dysfunction in pulmonary disorders in relation to respiratory acidosis, impaired gas exchange, systemic congestion, respiratory support/replacement therapies, and other issues relevant to the clinical care of these patients. Biotrauma due to injurious ventilatory strategies can lead to the release of mediators into the lung, which may then translocate into the systemic circulation and cause end-organ dysfunction, including renal dysfunction. Right ventricular dysfunction and congestive states may contribute to alterations of renal perfusion and oxygenation, leading to diuretic resistance and recurrent hospitalization. In patients with concomitant respiratory failure, noninvasive ventilation represents a promising treatment option for the correction of impaired renal microcirculation and endothelial dysfunction. In patients requiring extracorporeal membrane oxygenation, short- and long-term monitoring of kidney function is warranted, as they are at highest risk of developing acute kidney injury and fluid overload.
Low-Dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor–Negative Early Breast Cancer: International Breast Cancer Study Group Trial 22-00
Authors: Marco Colleoni, Kathryn P. Gray, Shari Gelber, István Láng, Beat Thürlimann, Lorenzo Gianni, Ehtesham A. Abdi, Henry L. Gomez, Barbro K. Linderholm, Fabio Puglisi, Carlo Tondini, Elena Kralidis, Alexandru Eniu, Katia Cagossi, Daniel Rauch, Jacquie Chirgwin, Richard D. Gelber, Meredith M. Regan, Alan S. Coates, Karen N. Price, Giuseppe Viale, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2016)

Purpose To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer. Patients and Methods International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor– and progesterone receptor–negative (&lt; 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths. Results After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio [HR], 0.84; 95% CI, 0.66 to 1.06;P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%). Conclusion CM maintenance did not produce a significant reduction in DFS events in hormone receptor–negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population.
Results from a phase 2 study of enzalutamide (ENZA), an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer (TNBC).
Authors: Tiffany A. Traina, Kathy Miller, Denise A. Yardley, Joyce O'Shaughnessy, Javier Cortes, Ahmad Awada, Catherine Margaret Kelly, Maureen E. Trudeau, Peter Schmid, Luca Gianni, Laura García-Estevez, Rita Nanda, Foluso Olabisi Ademuyiwa, Stephen Chan, Joyce Leta Steinberg, Martha Elizabeth Blaney, Iulia Cristina Tudor, Hirdesh Uppal, Amy C. Peterson, Clifford A. Hudis
Journal: Journal of Clinical Oncology (2015)

1003 Background: The AR may be a therapeutic target for pts with androgen-driven TNBC. ENZA, a potent AR inhibitor, is approved in men with metastatic castration-resistant prostate cancer (mCRPC) and improves median PFS compared to bicalutamide in men with mCRPC (15.7 vs 5.8 mos; HR 0.44; p<0.0001). Methods: MDV3100-11 was an open-label, Simon 2-stage study evaluating single agent ENZA in advanced AR+ TNBC (AR >0% by IHC; NCT01889238). Pts could be prescreened for AR, and have non-measurable bone disease and unlimited prior regimens; CNS metastases or seizure history were exclusionary. The primary endpoint was clinical benefit (CR, PR or SD) at 16 wks (CBR16) in ‘Evaluable’ pts defined as having both AR IHC ≥10% and a response assessment. CBR24, PFS, response rate, and safety were assessed. An androgen-driven gene signature (Dx) was created from gene profiling and outcomes were assessed accordingly. Stage 2 enrolled if CBR16 was ≥3 of 26 Evaluable pts; H0 was rejected if CBR16 was ≥9 in 62 yielding 85% power at 5% significance to test against a 1-sided alternative (CBR16 ≥20%). Results: As of 16 JAN 2015, 404 samples were tested for AR IHC: 79% had AR >0%; 55% had AR ≥10%. 118 pts were treated with ENZA; 43 pts were not Evaluable (29 AR <10%; 14 AR ≥10% but no response assessment). Key outcomes in the defined populations are below as shown in the Table. Over 50% received ENZA as 1st or 2nd line; mPFS in these pts was 32 wks in Dx+ and 9 wks in Dx-. Two CRs and 5 PRs have been observed. Related AEs in ≥10% of 118 pts were fatigue (34%), nausea (25%), decreased appetite (13%), diarrhea and hot flush (10%). Fatigue (5%) was the only AE ≥ Grade 3 in ≥5%. Conclusions: This is the largest study of an AR inhibitor in TNBC. IHC results suggest AR prevalence is higher than previously reported. 47% of pts had an androgen-related gene signature (Dx+) and clinical outcomes appeared superior in this group. AEs from ENZA were consistent with its known profile. ENZA may represent a novel therapeutic option in pts with TNBC who would otherwise receive cytotoxic chemotherapy. Clinical trial information: NCT01889238. Evaluable n=75 Dx+ n=56 Dx- n=62 CBR16, % (95% CI) 35 (24-46) 39 (27-53) 11 (5-21) CBR24, % (95% CI) 29 (20-41) 36 (24-49) 7 (2-16) mPFS, wks (95% CI) 14 (8-19) 16 (10-32) 8 (7-13)
Moderate Exercise for Nonalcoholic Fatty Liver Disease
Authors: Stacey Prenner, Mary E. Rinella
Journal: JAMA Internal Medicine (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 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