tbuckley/cabot-search huggingface dataset:
Hematogenous extramedullary relapse in multiple myeloma ‐ a multicenter retrospective study in 127 patients
Authors: Irit Avivi, Yael C. Cohen, Anna Suska, Tamir Shragai, Gabor Mikala, Laurent Garderet, Gueye M. Seny, Sophia Glickman, David S. Jayabalan, Ruben Niesvizky, Alessandro Gozzetti, Katarzyna Wiśniewska‐Piąty, Anna Waszczuk‐Gajda, Lidia Usnarska‐Zubkiewicz, Iwona Hus, Renata Guzicka, Jakub Radocha, Vibor Milunovic, Julio Davila, Massimo Gentile, Jorge J. Castillo, Artur Jurczyszyn
Journal: American Journal of Hematology (2019)

The current study assesses the characteristics and outcomes of multiple myeloma (MM) patients, treated with novel agents for hematogenous extramedullary (HEMM) relapse. Consecutive patients diagnosed with HEMM between 2010-2018 were included. Patients' characteristics at diagnosis and at HEMM presentation, response to treatment, survival and factors predicting survival were recorded and analyzed. A group of 127 patients, all diagnosed with HEMM by imaging (87.3%) and/or biopsy (79%), were included. Of those, 44% were initially diagnosed with ISS3, 57% presented with plasmacytomas, and 30% had high-risk cytogenetics. Median time to HEMM was 32 months. In multivariate analysis, ISS3 and bone plasmacytoma predicted shorter time to HEMM (P = .005 and P = .008, respectively). Upfront autograft was associated with longer time to HEMM (P = .002). At HEMM, 32% of patients had no BM plasmacytosis, 20% had non-secretory disease and 43% had light-chain disease. Multiple HEMM sites were reported in 52% of patients, mostly involving soft tissue, skin (29%), and pleura/lung (25%). First treatment for HEMM included proteasome inhibitors (50%), immunomodulatory drugs (IMiDs) (39%), monoclonal antibodies (10%), and chemotherapy (53%). Overall response rate (ORR) was 57%. IMiDs were associated with higher ORR (HR 2.2, 95% CI 1.02-4.7, P = .04). Median survival from HEMM was 6 months (CI 95% 4.8-7.2). Failure to achieve ≥VGPR was the only significant factor for worse OS in multivariate analyses (HR = 9.87, CI 95% 2.35 - 39, P = .001). In conclusion, HEMM occurs within 3 years of initial myeloma diagnosis and is associated with dismal outcome. The IMiDs might provide a higher response rate, and achievement of ≥VGPR predicts longer survival.
Comparison of Clinical Trial Changes in Primary Outcome and Reported Intervention Effect Size Between Trial Registration and Publication
Authors: Tao Chen, Chao Li, Rui Qin, Yang Wang, Dahai Yu, James Dodd, Duolao Wang, Victoria Cornelius
Journal: JAMA Network Open (2019)

Primary outcome change could threaten the validity of a clinical trial; however, evidence about the consequences on the reported intervention effect size is unclear.To examine the status of randomized clinical trials whose primary outcome changed between trial registration and publication and to quantify the association of this change with the reported intervention effect size.In this cross-sectional study on the primary report of randomized clinical trials with clear prospectively registered primary outcomes, PubMed and Embase were searched for articles published between January 1, 2011, and December 31, 2015. The search was conducted in January 2016, identifying randomized clinical trials and the combination of keywords and text words related to registry.Based on the developed approach, trials were classified as having primary outcome change when there was a major discrepancy between the registered and published primary outcomes. Intervention effect was estimated or recalculated using the odds ratio (OR) for each comparison. Each component OR is structured so that an OR is less than 1 if the intervention group has a more favorable result than the control group. The ratio of ORs (ROR), which is the summary OR for trials with primary outcome change divided by those without, and its 95% CI were calculated, with a value less than 1 indicating a larger reported intervention effect size in trials with primary outcome change than those without.Among 29 749 searched articles (28 810 MEDLINE and 939 Embase), 1488 articles were randomly selected for review. Of 389 trials with clear primary outcomes prospectively described in the registry (416 outcomes reported), 33.4% (130 of 389) of trials had at least 1 primary outcome change. Most (66 of 130) of the changes were either not reporting or omitting the primary outcome. In total, 338 trials (365 outcomes and 487 comparisons) were available for quantitative analysis on the reported intervention effect size bias assessment. Compared with those without primary outcome change, trials with primary outcome change showed a 16% (pooled ROR, 0.84; 95% CI, 0.73-0.96) larger reported intervention effect size. The result persisted after adjustment for potential confounders (ROR, 0.81; 95% CI, 0.71-0.93) and other sensitivity and subgroup analyses.Results of this study suggest that inconsistencies between registered and published primary outcomes of clinical trials are common, and trials with primary outcome change are likely to have a larger intervention effect than those without.
EBV-negative post-transplant lymphoproliferative disorder: Clinical characteristics, response to therapy, and survival.
Authors: Daniel S. Heil, Marlise Rachael Luskin, Edward Allen Stadtmauer, Stephen J. Schuster, Donald Edward Tsai, Ran Reshef
Journal: Journal of Clinical Oncology (2013)

8578 Background: Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of solid organ transplantation. PTLD is frequently linked with Epstein-Barr virus (EBV) and it was suggested that EBV negativity is associated with a poor prognosis and lack of response to reduction of immunosuppression (RI). We conducted a case-control study to identify the characteristics, outcome and response to therapy of EBVpos and EBVneg PTLD over a 20-year period. Methods: We reviewed data on patients diagnosed with PTLD at U. Penn. between 1982 and 2012. We determined EBV positivity on tumor samples according to WHO criteria. We compared clinical and pathologic characteristics, response to therapy, and survival of EBVpos and EBVneg patients. Results: Of 222 patients diagnosed with PTLD, we verified the EBV status of 169 patients, of whom 35% were EBVneg and 65% were EBVpos. Mean follow-up was 46.7 months. Median time from transplant to PTLD was 23.1 mo. in EBVpos vs. 59.3 mo. in EBVneg (p=0.003) with 42% of EBVpos patients being diagnosed within the first year after transplant vs. 15% in the EBVneg group (p&lt;0.001). EBVneg PTLD was more likely to occur in non-thoracic vs. thoracic transplants (p=0.006). 28% of patients with EBVpos PTLD presented with disease originating from the graft vs. 14% in the EBVneg group (p=0.03). In terms of histology, 36% of EBVpos patients had polymorphic PTLD vs. 7% of EBVneg patients (p&lt;0.001). Of patients who were treated with RI alone (40% of patients in both groups), the overall response rates were 50% and 48% in EBVpos and EBVneg patients respectively (p=NS). Response rates to rituximab were also similar. There was no difference in the mortality risk between groups (HR=1.04; p=0.84). The 5-year survival rates were 47% and 51% in EBVpos and EBVneg PTLD respectively (p=NS). Conclusions: In a large single-center series, EBVneg PTLD was associated with late occurrence after transplant, monomorphic histology and similar outcome in comparison with EBVpos PTLD. Importantly, the response of EBVneg PTLD to RI and rituximab was no different than EBVpos PTLD. These results have implications for the management of solid organ transplant recipients with PTLD.
Weekly topotecan and biweekly bevacizumab in recurrent and progressive ovarian carcinoma: A single institution experience for third-line or greater treatment.
Authors: Kassondra S Grzankowski, Shashikant B. Lele, John Pietkiewicz
Journal: Journal of Clinical Oncology (2013)

e16553 Background: The toxicity and efficacy of combined weekly topotecan and weekly bevacizumab in women with recurrent and progressive ovarian cancer. Methods: Reviewed data-base from 1/2003-present (1/2013) identified 15 patients who were treated with topotecan 4mg/m2 on days 1, 8, and 15 and bevacizumab 10mg/kg on days 1 and 15 of a 28-day cycle until progressive disease or excessive toxicity warranted discontinuation. The primary endpoint was progression-free survival. Results: Patients (n = 15) received a median of 4 treatment cycles. Mean number of previous chemotherapy regimens was 5 (range 2-9). Toxicity was generally mild, with neutropenia (20%), gastrointestinal toxicity (20%), pain (26%), anemia requiring transfusion (6%) being the most common adverse events. Two patients required dose adjustment secondary to neutropenia. Patients treated with 5 or more prior regimens had more adverse events, 66% vs. 33%, respectively. No febrile neutropenia or treatment-related deaths occurred. Median PFS and OS were 5.6 months and 5.9 months with 6 (40%) patients progression-free for ≥5 months. Two (13%) patients had complete response, 9 (60%) had stable disease or partial response and were still receiving the above mentioned treatment, and 4 (27%) had progressive disease. Conclusions: Treatment of recurrent and progressive ovarian cancer with weekly Topotecan and biweekly Bevacizumab demonstrates a viable efficacy with acceptable toxicity profile in women with previous multiple lines of treatment; as this becomes a more widely used regimen further investigation will be needed to determine early use of this well tolerated chemotherapy.
European <i>Echinococcus multilocularis</i> Identified in Patients in Canada
Authors: Alessandro Massolo, Claudia Klein, Kinga Kowalewska-Grochowska, Sara Belga, Clayton MacDonald, Stephen Vaughan, Safwat Girgis, Dimitri Giunchi, Sarah A Bramer, Maria A Santa, Danielle M Grant, Kensuke Mori, Padraig Duignan, Owen Slater, Bruno Gottstein, Norbert Müller, Stan Houston
Journal: New England Journal of Medicine (2019)

Echinococcus in Canada This report describes the emergence of a European form of Echinococcus multilocularis that was identified in Canadian wildlife and was associated with human illness.
Differential effects of selenium (Se) on normal and malignant cells treated with chemotherapy (CT) and radiation (RT).
Authors: Michael B. Jameson, Richard J Lobb, Gregory M Jacobson, Ray T Cursons
Journal: Journal of Clinical Oncology (2013)

e13583 Background: Preclinical work has demonstrated that Se compounds potentiate anticancer effects of CT and RT while reducing normal tissue toxicities. The molecular basis for the therapeutic selectivity has yet to be fully elucidated but includes modulation of intracellular glutathione (GSH) concentrations, endoplasmic reticulum (ER) stress responses, DNA repair, induction of apoptosis and cellular resistance to CT and RT. Our aim was to evaluate the dose-response relationship of the Se compound methylseleninic acid (MSA) on molecular pathways involved in the response of normal and malignant cells to CT and RT. Methods: Peripheral blood mononuclear cells (PBMC) obtained from healthy blood donors and malignant THP-1 human monocytic leukaemia cells were exposed in vitro to MSA 2.5, 5 or 15 µM in varying combinations with MSA, RT, cisplatin (Pt), doxorubicin (Dox) and cytosine arabinoside (Ara-C). GSH concentration was measured by ELISA, DNA damage and repair by COMET assay, cell viability by MTT assay and ER stress response protein expression by western blotting. Results: MSA was selectively toxic to THP-1 cells and induced a protective increase in GSH in PBMC but a decrease in high concentrations within THP-1 cells. DNA damage induced by Ara-C or Dox in the COMET assay was significantly reduced by MSA in PBMC but increased in THP-1 cells. Cell death after 2 Gy RT was increased by all doses of MSA in THP-1 cells but only by the highest dose in PBMC. The cytotoxicity of Dox and Ara-C at sublethal doses was significantly enhanced by MSA in THP-1 cells and to a lesser extent in PBMC, but MSA increased cell death from Pt only in THP-1 cells. MSA induced a protective ER stress response in PBMC exposed to Ara-C but an apoptotic response in THP-1 cells. Conclusions: MSA at clinically-relevant concentrations had a differential effect on cell survival and death responses to RT and CT with relative protection of PBMC and enhanced death of THP-1 cells. Several mechanisms mediated this therapeutic selectivity and the dose-dependence of the Se effect varied between malignant and normal cells. These assays could potentially be used in clinical trials to evaluate pharmacodynamic markers of Se effects in conjunction with CT and/or RT.
Acute Venous Thromboembolism Risk Highest Within 60 Days After Discharge From the Hospital in Patients With Inflammatory Bowel Diseases
Authors: Adam S. Faye, Timothy Wen, Ashwin N. Ananthakrishnan, Simon Lichtiger, Gilaad G. Kaplan, Alexander M. Friedman, Garrett Lawlor, Jason D. Wright, Frank J. Attenello, William J. Mack, Benjamin Lebwohl
Journal: Clinical Gastroenterology and Hepatology (2019)
Whose words are these? Statements derived from Facilitated Communication and Rapid Prompting Method undermine the credibility of Jaswal &amp; Akhtar's social motivation hypotheses
Authors: Stuart Vyse, Bronwyn Hemsley, Russell Lang, Scott O. Lilienfeld, Mark P. Mostert, Henry D. Schlinger, Howard C. Shane, Mark Sherry, James T. Todd
Journal: Behavioral and Brain Sciences (2019)

Abstract Jaswal &amp; Akhtar provide several quotes ostensibly from people with autism but obtained via the discredited techniques of Facilitated Communication and the Rapid Prompting Method, and they do not acknowledge the use of these techniques. As a result, their argument is substantially less convincing than they assert, and the article lacks transparency.
A randomized, double-blinded, placebo-controlled, multi-institutional, cross-over, phase II.5 study of saracatinib (AZD0530), a selective Src kinase inhibitor, in patients with recurrent osteosarcoma localized to the lung.
Authors: Kristin Baird, Denise K. Reinke, Joseph Gerald Pressey, Leo Mascarenhas, Noah Federman, Neyssa Marina, Sant P. Chawla, Joanne Pigues Lagmay, John M. Goldberg, Mohammed M. Milhem, David Mark Loeb, James E. Butrynski, Katherine A. Janeway, Brian Turpin, Arthur P. Staddon, Sheri L. Spunt, Eve T. Rodler, Scott Schuetze, Scott H. Okuno, Lee J. Helman
Journal: Journal of Clinical Oncology (2013)

TPS10591 Background: Osteosarcoma is a rare cancer and 33% of patients who have completed primary treatment will recur. The Src pathway has been implicated in the metastatic behavior of several tumors including osteosarcoma where 95% of samples express Src or have evidence of downstream activation of this pathway. Saracatinib (AZD0530) is a potent and selective Src kinase inhibitor. The recommended phase II dose in adults was found to be 175mg daily. The primary goal of this study is to determine if treatment with Saracatinib can increase progression free survival (PFS) for patients who have undergone complete resection of metastatic osteosarcoma nodules in the lung. Secondary goals are evaluation of overall survival, time to treatment failure, and evaluation of several biological correlatives. Methods: This is a multi-institutional, phase II.5, placebo-controlled study with an accrual goals of 88 randomized patients. Patients between 15 and 75 years, with histological confirmation of recurrent osteosarcoma, localized to the lung, who have potential for complete surgical resection, are eligible for enrollment. After complete resection, patients are randomized to treatment with saracatinib or placebo, of a daily oral dose of 175 mg, continuously for up to 1 year or until progression. Patients who recur in the lung while on-study and who are amenable to complete surgical resection will be un-blinded. Those patients who received placebo may have the option to undergo surgical resection. If fully resected, they will be offered therapy with saracatinib under the same treatment guidelines as above. As of January 2013, 38 patients have enrolled and 32 patients met the criteria to be randomized and began oral therapy with either saracatinib or placebo. An interim analysis is planned after 40 patients have been randomized. Clinical trial information: NCT00752206.
Diarrhea events in cancer patients (pts) treated with lapatinib
Authors: M. Koehler, S. Chan, B. O. Newstat, A. Preston, H. A. Burris
Journal: Journal of Clinical Oncology (2007)

9125 Introduction: Lapatinib (L) is an oral dual ErbB1/ErbB2 tyrosine kinase inhibitor administered to &gt; 5,000 pts in clinical trials. Low grade gastrointestinal adverse events: diarrhea, nausea and vomiting were recorded. We characterize here the diarrhea events related to L. Methods: Diarrhea events were recorded in 1,514 pts from 8 completed MBC and non-breast cancer clinical trials. Non-L treated pts in these trials were the comparator for analysis of toxicity grades, relationship to dose, time to onset, duration, required interventions and outcomes. Results: The L dose ranged from 1,000–1,500mg daily as monotherapy (n=928) or in combination with chemotherapy (n=198). Capecitabine alone (n=191)and tamoxifen alone (n=197) pts served as controls. For L and non-L groups the per pt diarrhea rates were: any grade 50%v33%; of those G1 54%v53%; G2 30%v30%; G3 15%v17%; G4 &lt;1%v0% and SAEs 3% v 3%; respectively. There were no fatal L-related SAEs. For L, early diarrhea presentation &lt;6 days(d) was 2x more frequent (44%v21%). In the non-L grp, diarrhea presented at 6–14 d in 30% pts. Delayed onset (&gt;28 d) was similar: 22% on L v 26%, non-L. Initial G3 diarrhea or progression from G1/G2 to G3 was similar (Lv non-L): 4%v 3% and 4% v3%, respectively. The median number of events/pt (2) was the same for both groups and median duration was 5d (L) v 6d (non-L). Events (L v non-L) resolved in 89%v93%; and resolved with sequelae &lt;1% v 1%; resolution was not recorded in 7%v4%. Events were managed in approximately 30% of pts with standard anti-diarrhea medications (loperimide and lomitil) and when more sever with hydration, octreotide &amp; antibiotics. Majority of G1/G2 events were not treated. Most pts (85%) did not have L interrupted or dose adjusted and both group only 2% (L)v 2% (non-L) discontinued therapy due to diarrhea. Conclusions: Diarrhea related to L therapy (mostly used as monotherapy in this analysis) is usually mild to moderate, frequently does not require intervention, but pts monitoring is crucial. Importantly, L-related diarrhea appears as early events (before day 6) and is generally responsive to standard interventions. Analyses are ongoing to further identify its natural history, characteristics and pts at risk for serious events. No significant financial relationships to disclose.
Correction to: Functional outcomes in adult patients with herpes simplex encephalitis admitted to the ICU: a multicenter cohort study
Authors: P. Jaquet, E. de Montmollin, C. Dupuis, C. Sazio, M. Conrad, V. Susset, S. Demeret, J. M. Tadie, L. Argaud, F. Barbier, B. Sarton, R. Chabane, D. Daubin, N. Brulé, N. Lerolle, M. Alves, D. Da Silva, A. El Kalioubi, S. Silva, P. Bailly, M. Wolff, L. Bouadma, J. F. Timsit, R. Sonneville
Journal: Intensive Care Medicine (2019)
Bad to the Bone
Authors: Jennifer L. Crombie, Ramkumar Venkateswaran, Annette S. Kim, Anand Vaidya, David C. Fisher
Journal: New England Journal of Medicine (2019)

A 52-year-old man presented to the emergency department with nausea, vomiting, and profound lethargy. He had noted mild nausea and fatigue for approximately 5 months. Given acute worsening of his symptoms in the days leading up to presentation, he sought medical care. He reported no associated fever, diarrhea, or abdominal pain but had had a weight loss of approximately 7 kg since the onset of symptoms. . . .
Response to: ‘On using machine learning algorithms to define clinically meaningful patient subgroups’ by Pinal-Fernandez and Mammen
Authors: Olivier Benveniste, Yves Allenbach, Benjamin Granger
Journal: Annals of the Rheumatic Diseases (2019)

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Long Noncoding RNA FAM225A Promotes Nasopharyngeal Carcinoma Tumorigenesis and Metastasis by Acting as ceRNA to Sponge miR-590-3p/miR-1275 and Upregulate ITGB3
Authors: Zi-Qi Zheng, Zhi-Xuan Li, Guan-Qun Zhou, Li Lin, Lu-Lu Zhang, Jia-Wei Lv, Xiao-Dan Huang, Rui-Qi Liu, FoPing Chen, Xiao-Jun He, Jia Kou, Jian Zhang, Xin Wen, Ying-Qin Li, Jun Ma, Na Liu, Ying Sun
Journal: Cancer Research (2019)

Long noncoding RNAs (lncRNA) play important roles in the tumorigenesis and progression of cancers. However, the clinical significance of lncRNAs and their regulatory mechanisms in nasopharyngeal carcinogenesis (NPC) are largely unknown. Here, based on a microarray analysis, we identified 384 dysregulated lncRNAs, of which, FAM225A was one of the most upregulated lncRNAs in NPC. FAM225A significantly associated with poor survival in NPC. N(6)-Methyladenosine (m6A) was highly enriched within FAM225A and enhanced its RNA stability. FAM225A functioned as an oncogenic lncRNA that promoted NPC cell proliferation, migration, invasion, tumor growth, and metastasis. Mechanistically, FAM225A functioned as a competing endogenous RNA (ceRNA) for sponging miR-590-3p and miR-1275, leading to the upregulation of their target integrin β3 (ITGB3), and the activation of FAK/PI3K/Akt signaling to promote NPC cell proliferation and invasion. In summary, our study reveals a potential ceRNA regulatory pathway in which FAM225A modulates ITGB3 expression by binding to miR-590-3p and miR-1275, ultimately promoting tumorigenesis and metastasis in NPC. SIGNIFICANCE: These findings demonstrate the clinical significance of the lncRNA FAM225A in nasopharyngeal carcinoma (NPC) and the regulatory mechanism involved in NPC development and progression, providing a novel prognostic indicator and promising therapeutic target.
Necrolytic Migratory Erythema
Authors: Jia-Wei Liu, Yue-Tong Qian, Dong-Lai Ma
Journal: JAMA Dermatology (2019)

This case report describes a man in his 40s who presented with a 7-year history of a pruritic, annular cutaneous eruption and flaccid vesicles and was diagnosed with glucagonoma syndrome and associated necrolytic migratory erythema.
The IL-37–Mex3B–Toll-like receptor 3 axis in epithelial cells in patients with eosinophilic chronic rhinosinusitis with nasal polyps
Authors: Jin-Xin Liu, Bo Liao, Qi-Hong Yu, Hai Wang, Yi-Bo Liu, Cui-Lian Guo, Zhi-Chao Wang, Zhi-Yong Li, Zhe-Zheng Wang, Jian-Wen Ruan, Li Pan, Yin Yao, Cai-Ling Chen, Heng Wang, Yuxia Liang, Guohua Zhen, Zheng Liu
Journal: Journal of Allergy and Clinical Immunology (2019)