tbuckley/cabot-search huggingface dataset:
Non-steroidal anti-inflammatory drugs for spinal pain: a systematic review and meta-analysis
Authors: Gustavo C Machado, Chris G Maher, Paulo H Ferreira, Richard O Day, Marina B Pinheiro, Manuela L Ferreira
Journal: Annals of the Rheumatic Diseases (2017)

While it is now clear that paracetamol is ineffective for spinal pain, there is not consensus on the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) for this condition. We performed a systematic review with meta-analysis to determine the efficacy and safety of NSAIDs for spinal pain.We searched MEDLINE, EMBASE, CINAHL, CENTRAL and LILACS for randomised controlled trials comparing the efficacy and safety of NSAIDs with placebo for spinal pain. Reviewers extracted data, assessed risk of bias and evaluated the quality of evidence using the Grade of Recommendations Assessment, Development and Evaluation approach. A between-group difference of 10 points (on a 0-100 scale) was used for pain and disability as the smallest worthwhile effect, as well as to calculate numbers needed to treat. Random-effects models were used to calculate mean differences or risk ratios with 95% CIs.We included 35 randomised placebo-controlled trials. NSAIDs reduced pain and disability, but provided clinically unimportant effects over placebo. Six participants (95% CI 4 to 10) needed to be treated with NSAIDs, rather than placebo, for one additional participant to achieve clinically important pain reduction. When looking at different types of spinal pain, outcomes or time points, in only 3 of the 14 analyses were the pooled treatment effects marginally above our threshold for clinical importance. NSAIDs increased the risk of gastrointestinal reactions by 2.5 times (95% CI 1.2 to 5.2), although the median duration of included trials was 7 days.NSAIDs are effective for spinal pain, but the magnitude of the difference in outcomes between the intervention and placebo groups is not clinically important. At present, there are no simple analgesics that provide clinically important effects for spinal pain over placebo. There is an urgent need to develop new drug therapies for this condition.
Effect of Tenapanor on Serum Phosphate in Patients Receiving Hemodialysis
Authors: Geoffrey A. Block, David P. Rosenbaum, Maria Leonsson-Zachrisson, Magnus Åstrand, Susanne Johansson, Mikael Knutsson, Anna Maria Langkilde, Glenn M. Chertow
Journal: Journal of the American Society of Nephrology (2017)

Hyperphosphatemia is common among patients with CKD stage 5D and is associated with morbidity and mortality. Current guidelines recommend lowering serum phosphate concentrations toward normal. Tenapanor is a minimally absorbed small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 that functions in the gut to reduce sodium and phosphate absorption. This randomized, double-blind, placebo-controlled trial assessed the effects of tenapanor on serum phosphate concentration in patients with hyperphosphatemia receiving hemodialysis. After a 1- to 3-week washout of phosphate binders, we randomly assigned 162 eligible patients (serum phosphate =6.0 to &lt;10.0 mg/dl and a 1.5-mg/dl increase from before washout) to one of six tenapanor regimens (3 or 30 mg once daily or 1, 3, 10, or 30 mg twice daily) or placebo for 4 weeks. The primary efficacy end point was change in serum phosphate concentration from baseline (randomization) to end of treatment. In total, 115 patients (71%) completed the study. Mean serum phosphate concentrations at baseline (after washout) were 7.32–7.92 mg/dl for tenapanor groups and 7.87 mg/dl for the placebo group. Tenapanor provided dose-dependent reductions in serum phosphate level from baseline (least squares mean change: tenapanor =0.47–1.98 mg/dl; placebo =0.54 mg/dl; P =0.01). Diarrhea was the most common adverse event (tenapanor =18%–68%; placebo =12%) and frequent at the highest tenapanor doses. In conclusion, tenapanor treatment resulted in statistically significant, dose-dependent reductions in serum phosphate concentrations in patients with hyperphosphatemia receiving hemodialysis. Additional studies are required to clarify the optimal dosing of tenapanor in patients with CKD-related hyperphosphatemia.
Cognition can affect perception: Restating the evidence of a top-down effect
Authors: Daniel T. Levin, Lewis J. Baker, Mahzarin R. Banaji
Journal: Behavioral and Brain Sciences (2016)

Abstract We argue that Firestone &amp; Scholl (F&amp;S) provide worthwhile recommendations but that their critique of research by Levin and Banaji (2006) is unfounded. In addition, we argue that F&amp;S apply unjustified level of skepticism about top-down effects relative to other broad hypotheses about the sources of perceptual intelligence.
Elotuzumab with lenalidomide and low-dose dexamethasone in patients with relapsed multiple myeloma: A randomized phase II study.
Authors: P. G. G. Richardson, P. Moreau, A. J. Jakubowiak, T. Facon, S. Jagannath, R. Vij, D. E. Reece, D. White, M. Raab, L. Benboubker, J. Rossi, C. Tsao, T. Parli, D. M. Berman, A. K. Singhal, S. Lonial
Journal: Journal of Clinical Oncology (2011)

8014 Background: Elotuzumab is a humanized monoclonal IgG1 antibody targeting human CS1, a cell surface glycoprotein. CS1 is highly and uniformly expressed on multiple myeloma (MM) cells, with limited expression on natural killer (NK) cells and CD8+ cells and little to no expression in normal tissues. A phase I trial of elotuzumab plus lenalidomide and low-dose dexamethasone demonstrated an 82% response rate in patients with relapsed/refractory MM. Methods: In this phase II study, previously treated MM patients were randomized to elotuzumab 10 or 20 mg/kg IV (days 1, 8, 15, and 22 every 28 days in first 2 cycles and days 1 and 15 of subsequent cycles), lenalidomide 25 mg PO (days 1–21) and dexamethasone 40 mg PO weekly. Prophylaxis for potential elotuzumab infusion-related adverse events (AEs) consisted of methylprednisolone (50 mg IV), diphenhydramine (25–50 mg PO or IV) or equivalent, ranitidine (50 mg IV) or equivalent, and acetaminophen (650–1000 mg PO). Treatment continued until disease progression or unacceptable toxicity. Objective responses were assessed according to IMWG criteria. Results: Among 63 enrolled patients (median age 63 years; range, 39–82), 57% had ≥2 prior therapies, 54% had prior bortezomib, and 59% had prior thalidomide. A total of 81% of patients had ≥ partial response (PR) including 37% ≥ very good PR (VGPR). The objective response rates (ORRs) were 90% in the 10 mg/kg group (n=31) and 72% in the 20 mg/kg group (n=32). Median time to response was 30 days (range, 21–100). The most common grade 3/4 treatment emergent toxicities were neutropenia (14%), lymphopenia (14%), and thrombocytopenia (13%). The most common infusion-reaction AEs were grade 1/2 nausea (16%), dizziness (13%), headache (13%), and pyrexia (10%). One patient had a grade 3 infusion reaction AE (rash). Conclusions: Elotuzumab plus lenalidomide/dexamethasone was generally well tolerated with manageable toxicity and resulted in a high ORR in patients with previously-treated MM. Further clinical study of this combination using 10 mg/kg elotuzumab is warranted. Updated results will be presented at the meeting.
Second interim analysis of the Global Investigation of Therapeutic Decisions in Unresectable HCC (uHCC) and of Its Treatment with Sorafenib (GIDEON): Differences in AE reporting across physician specialties.
Authors: Alan Paul Venook, Riccardo Lencioni, Jorge A. Marrero, Masatoshi Kudo, Keiko Nakajima, Sheng-Long Ye, Frank Cihon
Journal: Journal of Clinical Oncology (2012)

286 Background: GIDEON is an ongoing, global, prospective, non-interventional study of patients (pts) with uHCC receiving sorafenib (Sor) in real-life practice. Differences in pt management across physician specialties can be explored. Methods: The 2nd interim analysis was pre-planned when ~1500 treated pts were followed for ≥4 months. The predefined descriptive subgroup analysis by specialty is presented. Results: Median days between visits varied across specialties: medical oncologists (Med Oncs) had the shortest. Sor dosing was broadly similar across specialties, with hepatologists/gastroenterologists (Hep/GIs) having the greatest incidence of dose reductions. Most commonly reported (&gt;20% of pts) adverse events (AEs; e.g. diarrhea, hand-foot skin reaction [HFSR], fatigue) were similar across specialties, but the incidences varied. These AEs and grade 3/4 AEs were reported by more Hep/GIs and Med Oncs than by surgeons. The incidences of liver-related AEs varied across specialties. Interval-specific AE rates by specialty will be presented. Conclusions: Interim data from GIDEON highlight variations in the assessment and management of uHCC pts across specialties. The reporting of AEs and dose reductions may reflect the frequency of visits with physicians. Findings support the importance of a multidisciplinary team approach to optimize pt care. [Table: see text]
Graft vs. HTLV-I Virus Effect Can Be Induced Independently of Graft vs. Leukemia Effect in Patients with Adult T-Cell Leukemia Who Received Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Hiroshi Fujiwara, Makoto Yoshimitsu, Atsuo Ozaki, Tomohiro Kozako, Naomichi Arima, Chuwa Tei
Journal: Blood (2006)
Memory colours affect colour appearance
Authors: Christoph Witzel, Maria Olkkonen, Karl R. Gegenfurtner
Journal: Behavioral and Brain Sciences (2016)

Memory colour effects show that colour perception is affected by memory and prior knowledge and hence by cognition. None of Firestone & Scholl's (F&S's) potential pitfalls apply to our work on memory colours. We present a Bayesian model of colour appearance to illustrate that an interaction between perception and memory is plausible from the perspective of vision science.
Validation of a DNA Methylation Signature of Favorable Prognosis in Newly Diagnosed Acute Myeloid Leukemia.
Authors: Rodolphe F Taby, Sarvari Venkata Yellapragada, Heike Kroeger, Rong He, Steven M. Kornblau, Hagop Kantarjian, Farhad Ravandi, Jaroslav Jelinek, Jean-Pierre J Issa
Journal: Blood (2009)
Mother wins right to challenge prosecution for buying abortion pills in Northern Ireland
Authors: Clare Dyer
Journal: BMJ (2017)

A mother who faces criminal charges in Northern Ireland for procuring abortion pills over the internet for her 15 year old daughter has won permission from the High Court to challenge the prosecution as a breach of human rights.

In a case that will focus renewed attention on Northern Ireland’s draconian abortion laws, Lord Justice Weatherup and Mrs Justice Keegan gave permission to apply for a judicial review of the decision to prosecute. The judges said that the case raised “issues of considerable public …
The Need for Research on Treatments of Chronic Depression
Authors: Pim Cuijpers, Marcus J. H. Huibers, Toshi A. Furukawa
Journal: JAMA Psychiatry (2017)

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Impact of HOX11L2 and TAL1/SCL Expression in T-Cell Acute Lymphoblastic Leukaemia (T-ALL): Results of the FRALLE 93 Protocol.
Authors: Paola Ballerini, Jean-michel Cayuela, Vahid Asnafi, Sylvie Fasola, Marie-francoise Auclerc, Yves Perel, Odile Lejars5, Marianne Debre6, Gerard Michel7, Virginie Gandemer8, Brigitte Pautard9, Thierry Leblanc, Elizabeth Macintyre, Guy Leverger, Andre Baruchel, Judith Landman-Parker
Journal: Blood (2004)
Response of gastrointestinal stromal tumors (GISTs) to imatinib by Choi criteria and response evaluation criteria in solid tumors (RECIST) as surrogates for survival and time to progression
Authors: R. S. Benjamin, H. Choi, H. A. Macapinlac, M. A. Burgess, S. R. Patel, L. L. Chen, D. A. Podoloff, C. Chuslip
Journal: Journal of Clinical Oncology (2006)

9506 Background: Recent studies have demonstrated that RECIST is insensitive in evaluating GIST’s treated with imatinib. We have demonstrated in a small group of patients that a good response by Choi Criteria, i.e., a 10% decrease in unidimensional tumor size or a 15% decrease in tumor density on contrast-enhanced CT, correlated well with good response by PET (Proc. ASCO 22:819, 2003) and was more predictive of time to tumor progression (TTP) than response by RECIST (CTOS 2004). The aim of this study was to validate the correlation with disease-specific survival (DSS) and TTP with follow-up updated to 5-years. Methods: We evaluated 98 patients treated with imatinib for recurrent or metastatic GIST at our institution from December 2000 to September 2001 by RECIST and Choi criteria. All patients had pre-treatment and initial 2-monthly follow-up CT’s. DSS and TTP were analyzed by response category. Results: There were 28 (48%) good responders by RECIST and 30 (52%) poor responders. There were 49 (84%) good responders by Choi criteria, and 9 (16%) poor responders. Patients with good response by Choi criteria on CT at 8 weeks after treatment had significantly improved DSS (P = 0.04) in contrast to those with complete or partial response at any time by RECIST (P = 0.45). Similarly, TTP was significantly correlated with Choi response group (P = 0.01) but not with response group by RECIST (P = 0.74). Conclusions: Choi response criteria, incorporating tumor density and using small changes in tumor size on CT, are more sensitive and more accurate than RECIST in assessing the response of GISTs to imatinib mesylate and should be routinely incorporated into future studies of GIST therapy. Good response is detected earlier by Choi criteria and is a valid surrogate for DSS and TTP. We should desist using RECIST, at least in GIST. (Supported in part by NCI contracts U01-CA70172–01 and N01-CM-17003) [Table: see text]
Treosulfan-Based Preparative Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Children with Increased Risk of Conventional Regimen Toxicity.
Authors: Jacek Wachowiak, Alicja Chybicka, Jerzy Kowalczyk, Grzegorz Grund, Dariusz Boruczkowski, Ewa Gorczynska, Beata Wojcik, Michal Leda, Dominik Turkiewicz, Katarzyna Drabko
Journal: Blood (2005)
ATPS-70USING CYSTEINE KNOT PROTEINS TO RETARGET AN ONCOLYTIC VIRUS TO NOVEL CELL SURFACE ANTIGENS
Authors: Sangeet Lal, Corey Raffel
Journal: Neuro-Oncology (2015)

INTRODUCTION: Modified measles virus (MV) is an effective oncolytic virus and is currently being investigated in clinical trials for various cancer types.An advantage of MV is the ease of retargeting the virus to a receptor of choice.We investigated the use of cysteine knot proteins (CKP) to direct MV activity.CKP are short polypeptides that bind their targets with high affinity.A library of these proteins has been made, and a CKP that binds both av-b3 and av-b5 integrins with single digit nanomolar affinity has been isolated.We have used this CKP to target MV to the integrins.METHODS: We made a modified MV by inserting the integrin-binding CKP coding sequence at the carboxy-terminus of a mutated H protein that does not bind to its normal receptors (MV-CKP).We tested the virus for specificity for the integrins by assessing cell killing and MV replication in vitro.RESULTS: MV-CKP killed and replicated in U87 glioma cells, which express the target integrins.The virus did not kill and did not replicate in cells in which intregrin expression was knocked down with an av antisense lentivirus.MV-CKP activity was blocked by echistatin, an integrin binding peptide.When the CKP was cleaved from the virus at an inserted protease site, virus activity was abrogated.CONCLUSIONS: These results indicate that CKP can be used to selectively target MV.Because the integrins targeted are expressed by tumor endothelium and not by normal endothelium and because the CKP used has been shown to localize to tumor when injected IV, MV-CKP may be effective as IV therapy, a major step forward in the use of MV.In addition, the CKP library can be screened for other CKPs of interest.Lastly, the use of CKP to target viruses is applicable to many viruses other than MV.
EXPERT-C: A randomized phase II European multicenter trial of neoadjuvant chemotherapy (capecitabine/oxaliplatin) and chemoradiation (CRT) with or without cetuximab followed by total mesorectal excision (TME) in patients with MRI-defined high-risk rectal cancer.
Authors: A. Dewdney, D. Cunningham, J. Tabernero, B. Glimelius, A. Cervantes, D. M. Tait, G. Brown, A. Wotherspoon, D. Gonzalez de Castro, I. Chau
Journal: Journal of Clinical Oncology (2011)

360 Background: We previously demonstrated the feasibility of administering neoadjuvant chemotherapy before CRT and TME in patients with MRI selected poor prognosis rectal cancer (Chua Y J et al Lancet Oncol 2010). This trial evaluates the addition of the anti-EGFR antibody cetuximab to this treatment strategy. KRAS and BRAF mutations have been established as predictive for lack of response to anti-EGFR therapy in metastatic colorectal cancer. Methods: Patients with newly diagnosed, histologically confirmed, MRI defined high risk rectal adenocarcinoma were randomised to receive 4 cycles of capecitabine 1,700mg/m 2 with oxaliplatin 130mg/m 2 (CAPOX) followed by CRT, 45Gy/25# + 5.4Gy/3# boost with concurrent continuous capecitabine 1,650mg/m 2 /day, TME and 4 cycles of adjuvant CAPOX (EXPERT) or the same regimen with the addition of cetuximab (400mg/m 2 loading dose week 1, followed by 250mg/m 2 /week) (EXPERT-C). The primary endpoint is complete response (CR) (defined as pathological complete response or radiological complete response in patients who decline surgery) in KRAS and BRAF wild type tumours. Secondary endpoints include radiological response to CRT, CR in both KRAS wild type and mutant patients, R0 resection rates, progression free and overall survival and safety. Results: Between 2005-2008, 165 eligible patients were recruited from 15 centres (EXPERT n=81, EXPERT-C n=84). 99% of patients had performance status 0-1, 98% had ≥ T3 disease, 56% had an involved or threatened circumferential resection margin and 72% had evidence of extramural venous invasion determined by MRI. The current median follow up is 30 months. 72/81 (89%) and 79/84 (94%) of patients completed neoadjuvant CRT and 72/81 (89%) and 77/84 (92%) patients underwent curative-intent surgery on the EXPERT and EXPERT-C arms respectively. Two patients declined surgery. Conclusions: The primary and secondary endpoints will be analyzed in October 2010 and will be presented at the meeting. [Table: see text]
New treatment options for metastatic renal cell carcinoma with prior anti-angiogenesis therapy
Authors: Kevin Zarrabi, Chunhui Fang, Shenhong Wu
Journal: Journal of Hematology & Oncology (2017)

Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus. This review provides an in-depth summary of drugs employable in the clinical setting, the rationale to their use, and the studies conducted leading to their approval for use and provides perspective on the paradigm shift in the treatment of renal cell carcinoma. Highlighted are the newly approved agents cabozantinib, nivolumab, and lenvatinib for advanced renal cell carcinoma patients treated with prior anti-angiogenesis therapy.
RTRB-17NEURAL PROGENITOR CELL (NPC) SPARING RADIATION THERAPY PLUS TEMOZOLOMIDE IN NEWLY DIAGNOSED GLIOBLASTOMA (GBM) ASSOCIATED WITH COGNITIVE FUNCTION BUT NOT TUMOR OUTCOMES: RESULTS OF A SINGLE ARM PROSPECTIVE CLINICAL TRIAL
Authors: Kristin Redmond, Xiaobu Ye, Ryan Assadi, Riley McIntyre, Joseph Moore, Eric Ford, Stuart Grossman, Alfredo Quinones-Hinojosa, Lawrence Kleinberg, Tracy Vannorsdall
Journal: Neuro-Oncology (2015)

BACKGROUND: NPC may be associated with neuro-cognitive sequelae of RT, but may contribute to GBM recurrence. This prospective trial limited RT dose to NPC niches to evaluate the impact on neuro-cognitive function, tumor recurrence, and survival in newly diagnosed GBM. METHODS: 30 adults with newly diagnosed GBM and KPS > 60 enrolled. Each received 60 Gy in 30 fractions with concurrent/adjuvant temozolomide. Standard planning target volumes (PTV) delineated. Subventricular zone (SVZ, 0.5 cm adjacent to lateral wall of lateral ventricle) and hippocampus (expanded 5 mm) defined as NPC niches. IMRT limited RT dose to NPC niches without compromising PTV dose. Tests of global cognitive function, processing speed, verbal learning/memory, and executive function obtained at baseline, 6, 12, 24 months. OS/PFS estimated using Kaplan-Meier method. Cox regression model evaluated relationships between performance on cognitive testing, radiation doses to NPC regions, survival outcomes. RESULTS: 16 men, 14 women; 17 gross total resection, 13 subtotal resection; 8 MGMT methylated, 11 unmethylated, 10 unknown; 6 multifocal. Median OS: 15.9 months (95% CI 12.6-35.4). Median PFS: 7.3 months (95% CI 4.8-9.3 months). Mean dose to ipsilateral and contralateral hippocampus: 43.8 Gy (range 9.0 - 61.4) and 17.3 Gy (range 1.7 - 40.2), respectively. Mean dose to ipsilateral and contralateral SVZ: 38.9 Gy (range 6 - 56.2) and 20.5 Gy (range 4.4 - 48.0), respectively. At a minimum FU of 13 months, 2 patients recurred in spared NPC volume. Higher mean RT dose to bilateral SVZ was associated with greater deterioration in performance between baseline and 6 /12 months on processing speed (Coding, p = 0.03). No relationship between RT dose to NPC niches and PFS, OS, or recurrence patterns. CONCLUSIONS: This prospective trial suggests a relationship between RT dose to NPC niches and neuro-psychological function in newly diagnosed GBM without a detrimental effect on recurrence or survival outcomes.
G17V Rhoa Mutation in Circulating DNA Is a Useful Marker for Diagnosis of AITL and AITL-Related Lymphoma
Authors: Rie Nakamoto-Matsubara, Mamiko Sakata-Yanagimoto, Tran Nguyen, Junichi Furuta, Takayoshi Ito, Takuya Komeno, Seishi Ogawa, Shigeru Chiba
Journal: Blood (2015)