tbuckley/cabot-search huggingface dataset:
Temporal cessation of sunitinib treatment in patients with metastatic renal cell carcinoma: A retrospective study.
Authors: Yuji Miura, Yoichi Fujii, Akihiko Shimomura, Naoki Sudo, Masaomi Ikeda, Koichi Suyama, Mitsuhiro Abe, Shuji Kameyama, Toshikazu Okaneya, Toshimi Takano
Journal: Journal of Clinical Oncology (2014)

e15552 Background: Sunitinib is a multi-targeted receptor tyrosine kinase inhibitor against vascular endothelial growth factor receptors (VEGFR), platelet derived growth factor receptors and other receptors. Sunitinib showed dramatically improved clinical outcome in advanced renal cell carcinoma (RCC); however, it is difficult to manage the balance of toxicity and efficacy of sunitinib. Therefore, high percentages of patients who receive sunitinib have to discontinue the treatment due to toxicities. The information on whether the initial response to sunitinib can maintain disease control after temporal cessation of sunitinib is limited. Methods: A retrospective study of patients with metastatic RCC who initiated sunitinib between December 2010 and January 2013 at Toranomon Hospital and NTT Medical Center Tokyo was conducted. Patients who maintained RECIST-defined stable disease or better for more than 3 months, and followed discontinuation all therapy due to toxicity were included. We retrospectively investigated progression-free survival (PFS) from discontinuation to progressive disease (PD), response to the following therapy, and toxicity during discontinuation, based on review of their medical records. Results: Nine patients were identified. Their median age was 69 years. One patient had prior systemic therapy history of temsirolimus; meanwhile, the remaining eight patients had no prior systemic therapy. Median follow up after cessation of sunitinib was 10.9 months. Six of nine had PD during cessation, and median PFS was 5.5 months (95% confidence interval 2.0 to 8.9). No patient had radiographic and clinical “flare” phenomenon (rapid and unexpected PD) after cessation. Sunitinib-induced toxicity totally resolved during treatment cessation. Four of the six patients who had had PD re-initiated sunitinib, and the remaining two patients switched to axitinib because of unacceptable toxicity of sunitinib. All of them had radiological response by recommencing of VEGFR inhibitors. Conclusions: Temporal cessation of sunitinib might be feasible with maintaining disease control and resolving toxicity. Further prospective investigation on this treatment strategy is warranted.
Comparison of Reduced Intensity Conditioning (RIC) Regimen and Myeloablative Conditioning (MAC) Regimen in Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) for Adult Patients with Acute Leukemia
Authors: Gunhan Gurman, Gozde Aydemir Guloksuz, Erden Atilla, Pinar Ataca Atilla, Sinem Civriz Bozdag, Meltem Kurt Yuksel, Selami Kocak Toprak, Pervin Topcuoglu, Onder Arslan, Muhit Ozcan, Taner Demirer, Osman Ilhan, Hamdi Akan, Meral Beksac
Journal: Blood (2016)
Antihypertensive Drugs and Renal Protection
Authors: Michio Fukuda, Takeshi Usami, Atsuhiro Yoshida, Genjiro Kimura
Journal: JAMA (2003)

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 Journals 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
Results of a phase 1b study of venetoclax plus decitabine or azacitidine in untreated acute myeloid leukemia patients ≥ 65 years ineligible for standard induction therapy.
Authors: Daniel Aaron Pollyea, Courtney Denton Dinardo, Michael J. Thirman, Anthony Letai, Andrew H. Wei, Brian Andrew Jonas, Martha Lucia Arellano, Mark G Frattini, Hagop M Kantarjian, Brenda Chyla, Ming Zhu, Jalaja Potluri, Rod Humerickhouse, Mack H. Mabry, Marina Konopleva, Keith William Pratz
Journal: Journal of Clinical Oncology (2016)

7009 Background: Venetoclax (VEN) is a potent, orally bioavailable BCL-2 inhibitor with single-agent activity in relapsed/refractory acute myeloid leukemia (AML) patients (pts), displaying synergistic activity with hypomethylating agents in preclinical studies. This trial evaluates VEN plus decitabine (DEC) or azacitidine (AZA) in treatment (Tx)-naive AML pts ≥ 65 y (NCT02203773). Methods: Tx-naive pts (ECOG PS ≤ 2, ≥ 65 y, intermediate- or poor-risk karyotype) not eligible for standard induction therapy received DEC (Arm A: 20 mg/m2 iv) daily on days (D) 1−5 or AZA (Arm B: 75 mg/m2; subcutaneous or iv) daily on D 1−7 of each 28-D cycle in combination with once-daily continuous oral VEN. VEN dose escalation follows a 3+3 design; 1200 mg is the final dose level. Objectives include safety, preliminary efficacy, and biomarker evaluations. Results: As of 11/28/15, 39 pts (49% male; median age 74 y [65–85 y]) have been enrolled in Arm A (n = 20) and Arm B (n = 19). Median time on study is111 D (6−375 D); 16 pts (41%) remain on therapy. Biomarker analysis and response evaluations have been completed in 34 pts with 400-mg and 800-mg VEN doses. As of 9/19/15, overall response rate (ORR; complete response [CR]/CR with incomplete marrow recovery [CRi]/partial remission [PR]) within this population was 76% (CR: 13/CRi: 11/PR: 2; 26/34 pts). Poor-risk cytogenetics and IDH1/2 mutations were reported in 24% (8/34) and 32% (11/34) of pts; ORR was 88% (7/8) and 82% (9/11), respectively. Median time to CR/CRi was 29.5 D (24−112 D). Most common TEAEs were nausea (54%), febrile neutropenia (41%), diarrhea (44%), decreased appetite (33%), and peripheral edema (31%). No dose-limiting toxicity was reported. Febrile neutropenia (41%) and neutropenia (33%) were the most common Grade 3/4 TEAEs. Most frequent serious AE was febrile neutropenia (28%). Four relapses occurred, all on Arm A. Six deaths occurred (3 disease progression, 1 sepsis, 1 respiratory failure, 1 bacteremia). MTD has not been reached. Conclusions: Tx with VEN plus DEC or AZA shows a tolerable safety profile, with high response rates observed in Tx-naive AML pts ≥ 65 y, including those with adverse biologic disease features. Clinical trial information: NCT02203773.
ATF3 Repression of BCL-XL Determines Apoptotic Sensitivity to HDAC Inhibitors across Tumor Types
Authors: Anderly C. Chüeh, Janson W.T. Tse, Michael Dickinson, Paul Ioannidis, Laura Jenkins, Lars Togel, BeeShin Tan, Ian Luk, Mercedes Davalos-Salas, Rebecca Nightingale, Matthew R. Thompson, Bryan R.G. Williams, Guillaume Lessene, Erinna F. Lee, Walter D. Fairlie, Amardeep S. Dhillon, John M. Mariadason
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Histone deacetylase inhibitors (HDACi) are epigenome-targeting small molecules approved for the treatment of cutaneous T-cell lymphoma and multiple myeloma. They have also demonstrated clinical activity in acute myelogenous leukemia, non–small cell lung cancer, and estrogen receptor–positive breast cancer, and trials are underway assessing their activity in combination regimens including immunotherapy. However, there is currently no clear strategy to reliably predict HDACi sensitivity. In colon cancer cells, apoptotic sensitivity to HDACi is associated with transcriptional induction of multiple immediate-early (IE) genes. Here, we examined whether this transcriptional response predicts HDACi sensitivity across tumor type and investigated the mechanism by which it triggers apoptosis. Experimental Design: Fifty cancer cell lines from diverse tumor types were screened to establish the correlation between apoptotic sensitivity, induction of IE genes, and components of the intrinsic apoptotic pathway. Results: We show that sensitivity to HDACi across tumor types is predicted by induction of the IE genes FOS, JUN, and ATF3, but that only ATF3 is required for HDACi-induced apoptosis. We further demonstrate that the proapoptotic function of ATF3 is mediated through direct transcriptional repression of the prosurvival factor BCL-XL (BCL2L1). These findings provided the rationale for dual inhibition of HDAC and BCL-XL, which we show strongly cooperate to overcome inherent resistance to HDACi across diverse tumor cell types. Conclusions: These findings explain the heterogeneous responses of tumor cells to HDACi-induced apoptosis and suggest a framework for predicting response and expanding their therapeutic use in multiple cancer types.
Number needed to treat
Authors: P. Sedgwick
Journal: BMJ (2010)

Researchers compared the efficacy of foot orthoses with both flat inserts and multimodal physiotherapy in the management of patellofemoral pain syndrome. They used a single blind randomised controlled trial study design. A total of 179 participants were recruited and randomised to six weeks of physiotherapist intervention with off the shelf foot orthoses, flat inserts, or multimodal physiotherapy.1

Primary outcome measures included self assessment of change in pain at six weeks from baseline. Each participant recorded self perceived change in pain on a five point Likert scale (categorised as “marked improvement,” “improvement,” “neither improvement nor worsening,” “worsening,” or “marked worsening”). Global improvement was considered to be self reported marked or moderate improvement in pain.

At six weeks, a greater proportion of those allocated foot orthoses reported global improvement compared with those allocated flat inserts (85.4% v 57.5%), giving a relative risk of …
Impact of Postoperative Radiotherapy in Men with Persistently Elevated Prostate-specific Antigen After Radical Prostatectomy for Prostate Cancer: A Long-term Survival Analysis
Authors: Giorgio Gandaglia, Stephen A. Boorjian, William P. Parker, Emanuele Zaffuto, Nicola Fossati, Marco Bandini, Paolo Dell’Oglio, Nazareno Suardi, Francesco Montorsi, R. Jeffrey Karnes, Alberto Briganti
Journal: European Urology (2017)
Truncating mutations in RBM12 are associated with psychosis
Authors: Stacy Steinberg, Steinunn Gudmundsdottir, Gardar Sveinbjornsson, Jaana Suvisaari, Tiina Paunio, Minna Torniainen-Holm, Michael L Frigge, Gudrun A Jonsdottir, Johanna Huttenlocher, Sunna Arnarsdottir, Oddur Ingimarsson, Magnus Haraldsson, Thorarinn Tyrfingsson, Thorgeir E Thorgeirsson, Augustine Kong, Gudmundur L Norddahl, Daniel F Gudbjartsson, Engilbert Sigurdsson, Hreinn Stefansson, Kari Stefansson
Journal: Nature Genetics (2017)
Targeted radiofrequency ablation of metastatic posterior vertebral body lesions in patients with soft tissue sarcomas.
Authors: Jessica C. Ley, Jack Jennings, Jonathan C Baker, Travis Hillen, Brian Andrew Van Tine
Journal: Journal of Clinical Oncology (2013)

10585 Background: Metastatic spinal lesions can be debilitating with significant impact on patients quality of life. Concern for damage to adjacent neural elements during treatment exist due to high radiation doses required to treat certain radioresistant spinal lesions such as soft tissue sarcoma. Radiofrequency ablation (RFA) of metastatic lesions has been shown to be effective in bone. Spine anatomy presents challenges for minimally invasive (MI) treatment of posterior vertebral body lesions. Targeted RFA (t-RFA) using a novel tumor ablation system, designed for spinal anatomy is evaluated in patients with symptomatic posterior vertebral wall spinal lesions. Methods: Five patients with metastatic leiomyosarcoma or liposarcoma and posterior vertebral body spine lesions, treated by prior radiation with continued progression of lesion size and pain received t-RFA, using a novel spinal tumor ablation system (STAR, DFINE), which contains an articulating bipolar, extensible electrode for navigation. Device thermocouples (TC) permit real time monitoring of the ablation zones to determine size. Sequential post-procedural pain scores, PET and contrast enhanced magnetic resonance imaging, and histopathology of treated area was performed. Results: No complications or thermal injury occurred. Intra-procedural imaging demonstrated the articulated, bipolar instrument was able to navigate to posterior lesions. Post-ablation MRI demonstrated lesion necrosis within a discrete ablation zone. No evidence of malignancy by PET or histopathology was noted through 10 months. All patients reported post procedural pain relief. Systemic therapy was not interrupted. Conclusions: Navigational t-RFA proved a safe and effective, non-ionizing palliative therapy alternative for radio-resistant lesions . Post-ablation imaging and histology confirmed metastatic lesions were necrotic and included in ablation zone with tumor control 10 mos post treatment. Ablation zone was very consistent with real time temperature readings. t-RFA permitted MI targeted treatment of lesions within close proximity of spinal cord, not controlled by systemic therapy. Prospective clinical trial is under preparation.
In-home, Over-the-counter Sleep Apnea Sensor on the Horizon
Authors: Jennifer Abbasi
Journal: JAMA (2017)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
A phase I study of 1-methyl-D-tryptophan in patients with advanced malignancies.
Authors: Hatem Hussein Soliman, Anthony Neuger, David Noyes, Nicholas N. Vahanian, Charles J. Link, David Munn, Howard Streicher, Daniel Sullivan, Scott Antonia
Journal: Journal of Clinical Oncology (2012)

2501 Background: The indoleamine 2, 3 dioxygenase pathway (IDO) can create immune suppression and unresponsiveness to tumor antigens in tumor-bearing hosts. 1-methyl-D-tryptophan (1-MT) is an oral inhibitor of the IDO pathway, currently in development as an immune adjuvant for anti-tumor vaccines and chemotherapy. The primary goal of this trial is to determine the MTD and toxicity for oral 1-MT. Secondary endpoints include response rates, PK, serum tryptophan catabolites, circulating T-reg cells, and C reactive protein (CRP) levels. Methods: This phase I study utilizes a 3+3 design comprised of ten dose levels (200, 300,400,600,800,mg QD, 600, 800,1200,1600,2000mg BID). Inclusion criteria: patients with measurable metastatic solid malignancy, age ≥18, life expectancy &gt;4 months, and adequate organ/marrow function. Exclusion criteria: chemotherapy in the past 3 weeks, untreated brain metastases, active autoimmune disease, or malabsorptive GI disease. Continuous toxicity monitoring early stopping rules were used. Results: At submission, 48 out of the planned 50 patients were accrued. MTD was not reached at 2000mg BID. At 200mg QD dose, 3 patients previously treated with active immunotherapy (ipilimumab, n=2, CD40-mAb, n=1) developed an autoimmune hypophysitis. Since IDO is closely linked to both CTLA-4 and CD40/CD40L pathways this was considered on-target effect. Subsequently, patients with prior immunotherapy were excluded and no additional treatment related G3-5 adverse events were observed. Five patients showed SD&gt;6 months (2 melanoma, 2 sarcoma 1 colon) as well as some mixed responses were seen in some patients including regression of a liver visceral metastases. 1-MT plasma PK AUC and Cmax were proportional with dose. Cmax (~40 μM at 2000mg BID) is at 2.9 hours and the t1/2 is at 10 hours. Elevations in CRP levels and declines in T-reg cell counts were seen across multiple dose levels. Additional correlative data analysis is ongoing. Conclusions: The treatment was well tolerated and orally bioavailable. Biologic activity in terms of prolonged disease stabilization, induction of hypophysitis, and changes in T-reg levels and CRP were observed. Trials combining 1-MT with docetaxel and a dendritic cell vaccine are ongoing.
Alcohol: A Fibrogenic Cocktail in Genetic Haemochromatosis?
Authors: F Gleeson, E Ryan, J Crowe
Journal: Endoscopy (2004)

Background: The interpretation of moderate alcohol consumption varies worldwide. In Ireland, recommended sensible limits for men and women are no more than 21 IU and 14 IU of alcohol per week respectively. Excess alcohol consumption is thought to act as a fibrogenic cofactor in the progression of haemochromatosis.
Sixty seconds on . . . natural caesarean
Authors: Anne Gulland
Journal: BMJ (2017)

Sounds like it. But don’t worry, putting “natural” in front of caesarean section doesn’t mean doing without pain relief. It means slowing down the operation so that it mimics a vaginal birth as much as possible.

Surgery starts with the screen up and sterile procedures are followed as usual. But after the incision has been made the drape is lowered and the head of the table is raised to allow the mother …
Abstract 78: Transforming Growth Factor-β Induces the Cardiac Fibrosis and Remodeling in Guanylyl cyclase/Natriuretic Peptide Receptor-A Gene-Disrupted Null Mutant Mice
Authors: Kailash N Pandey, Umadevi Subramanian
Journal: Circulation Research (2015)

Genetic disruption of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) in mice exhibits high blood pressure, cardiac hypertrophy, fibrosis, and remodeling leading to congestive heart failure. The objective of this study was to determine the mechanisms regulating the development of fibrosis in Npr1 gene-disrupted mice hearts. The Npr1 null mutant (Npr1-/-, 0-copy), heterozygous (Npr1+/-, 1-copy), and wild-type (Npr1+/+, 2-copy) mice were administered by oral gavage with transforming growth factor-β1 (TGF- β1) receptor inhibitor GW788388 (1mg/kg/day) for 28 days. The heart tissues were isolated and used for quantification of fibrotic markers by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analyses. Together, systolic blood pressure (SBP), heart weight-to-body weight (HW/BW) ratio, left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVEDS), and percent fractional shortening (FS) were analyzed. The Npr1-/- null mutant mice hearts displayed 6-fold induction of fibrosis compared with wild-type (WT) Npr1+/+ mice. Furthermore, the increased expression of fibrotic markers as observed, including connective tissue growth factor (CTGF, 5-fold), α-smooth muscle actin (α-SMA, 4-fold) and TGF-β receptor I (TGF-βRI, 4-fold), TGF-β receptor II (TGF-βRII, 3.5-fold) and Smad2/3 proteins in Npr1-/- mice hearts compared with WT control mice. However, treatment with TGF-β receptor antagonist, GW788388, significantly prevented the cardiac fibrosis and down-regulated the expression of fibrotic markers and Smad proteins in Npr1-/- mice compared to vehicle-treated WT controls. The results of the present study suggest that the activation of cardiac fibrosis in Npr1-/- mice is mainly triggered through TGF-β mediated Smad-dependent pathways.
Stereotactic Radiotherapy for Neovascular Age-Related Macular Degeneration
Authors: Timothy L. Jackson, Usha Chakravarthy, Jason S. Slakter, Alyson Muldrew, E. Mark Shusterman, Denis O'Shaughnessy, Mark Arnoldussen, Michael E. Gertner, Linda Danielson, Darius M. Moshfeghi
Journal: Ophthalmology (2014)
Hemophagocytic lymphohistiocytosis as presenting manifestation of profound combined immunodeficiency due to an ORAI1 mutation
Authors: Christian Klemann, Sandra Ammann, Miriam Heizmann, Sebastian Fuchs, Sebastian F. Bode, Maximilian Heeg, Hans Fuchs, Kai Lehmberg, Udo zur Stadt, Claudia Roll, Thomas Vraetz, Carsten Speckmann, Myriam Ricarda Lorenz, Klaus Schwarz, Jan Rohr, Stefan Feske, Stephan Ehl
Journal: Journal of Allergy and Clinical Immunology (2017)
Toxicity, surgical complications, and short-term mortality in a randomized trial of neoadjuvant cisplatin/5FU versus epirubicin/cisplatin and capecitabine prior to resection of lower esophageal/gastroesophageal junction (GOJ) adenocarcinoma (MRC OEO5, ISRCTN01852072, CRUK 02/010).
Authors: David Cunningham, Derek Alderson, Matthew Guy Nankivell, Sally Patricia Stenning, Jane M. Blazeby, Michael Griffin, Adrian Crellin, Heike I. Grabsch, Stephen Falk, Alicia Frances Clare Okines, Claire Robb, Ruth E Langley
Journal: Journal of Clinical Oncology (2014)

4014 Background: Randomized trials have shown that neoadjuvant approaches improve survival following esophagectomy. Data on toxicities from the different approaches are often not reported in detail. Methods: OEO5 is a Cancer Research UK funded multi-centre, phase III randomized clinical trial for resectable (T1/2 N1 M0 to T3/4 N0/1 M0) adenocarcinoma of the lower esophagus and Type I/II GOJ. Patients were randomly allocated (1:1) to 2 cycles of cisplatin/5FU (CF) or 4 cycles of epirubicin/cisplatin and capecitabine (ECX) pre-operatively followed by esophagectomy with 2-field lymphadenectomy. The Independent Data Monitoring Committee and Trial Steering Committee agreed to release data on treatment related toxicities and deaths up to 90 days post-surgery. Overall survival is the primary outcome measure but is not yet mature; events having accrued more slowly than expected. Results: Between 2005 and 2011, 897 patients (median age 62 years (range 27-81), 90% male, 63% T3 N1, WHO PS 0-1) were randomly allocated to CF (451) or ECX (446). CF: 96% received 2 cycles, ECX: 81% received 4 cycles. Any grade 3/4 toxicity (CF 30%, ECX 47%, p<0.001), (CF v ECX: neutropenia 16% v 23%, diarrhoea 1% v 8% and plantar palmar erythema 0% v 9%). Median time (days) from randomisation (day 1 of last chemo cycle) to surgery (CF 72 (45), ECX 128(58)). Surgical data were available on 878 (CF 446, ECX 432) patients, with 84% reported as having resection and reconstruction. Post-operative complications reported in CF 54% and ECX 59% (life threatening complications CF 7% vs ECX 9%). No differences were seen in anastomotic leak rates (clinical 11%, radiologic only 5%), thromboembolic complications (4%) or deaths within 30 days of operation (2% both arms), or within 90 days (CF 4%, ECX 5%). Conclusions: Four cycles of ECX compared to 2 cycles of CF increased chemotherapy related toxicity, but did not affect resection rates, surgical complications or 90 day mortality. Clinical trial information: ISRCTN01852072.