tbuckley/cabot-search huggingface dataset:
Alcohol consumption and fecundability: prospective Danish cohort study
Authors: Ellen M Mikkelsen, Anders H Riis, Lauren A Wise, Elizabeth E Hatch, Kenneth J Rothman, Heidi T Cueto, Henrik Toft Sørensen
Journal: BMJ (2016)

<b>Objective</b> To investigate to what extent alcohol consumption affects female fecundability. <b>Design</b> Prospective cohort study. <b>Setting</b> Denmark, 1 June 2007 to 5 January 2016. <b>Participants</b> 6120 female Danish residents, aged 21-45 years, in a stable relationship with a male partner, who were trying to conceive and not receiving fertility treatment. <b>Main outcome measures</b> Alcohol consumption was self reported as beer (330 mL bottles), red or white wine (120 mL glasses), dessert wine (50 mL glasses), and spirits (20 mL) and categorized in standard servings per week (none, 1-3, 4-7, 8-13, and ≥14). Participants contributed menstrual cycles at risk until the report of pregnancy, start of fertility treatment, loss to follow-up, or end of observation (maximum 12 menstrual cycles). A proportional probability regression model was used to estimate fecundability ratios (cycle specific probability of conception among exposed women divided by that among unexposed women). <b>Results</b> 4210 (69%) participants achieved a pregnancy during follow-up. Median alcohol intake was 2.0 (interquartile range 0-3.5) servings per week. Compared with no alcohol consumption, the adjusted fecundability ratios for alcohol consumption of 1-3, 4-7, 8-13, and 14 or more servings per week were 0.97 (95% confidence interval 0.91 to 1.03), 1.01 (0.93 to 1.10), 1.01 (0.87 to 1.16) and 0.82 (0.60 to 1.12), respectively. Compared with no alcohol intake, the adjusted fecundability ratios for women who consumed only wine (≥3 servings), beer (≥3 servings), or spirits (≥2 servings) were 1.05 (0.91 to1.21), 0.92 (0.65 to 1.29), and 0.85 (0.61 to 1.17), respectively. The data did not distinguish between regular and binge drinking, which may be important if large amounts of alcohol are consumed during the fertile window. <b>Conclusion</b> Consumption of less than 14 servings of alcohol per week seemed to have no discernible effect on fertility. No appreciable difference in fecundability was observed by level of consumption of beer and wine.
Case 21-1974
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Melvin P. Osborne, Benjamin Castleman
Journal: New England Journal of Medicine (1974)

Presentation of Case*A 50-year-old man was admitted to the hospital because of gastrointestinal bleeding.For more than 20 years he had experienced epigastric burning that was relieved by antacids. Fourteen years before admission he had an acute anteroseptal myocardial infarct, from which he recovered without incident. Hypertension was found and was treated with an unknown medication. Three years before entry pain developed in the back and in the left leg, and examination disclosed a pulsatile epigastric mass. An abdominal aortic aneurysm was resected, and the symptoms disappeared.Nine months before admission he began to pass maroon stools. He entered . . .
A Randomized Comparison of Dexamethasone + Thalidomide (Dex/Thal) vs Dex + Placebo (Dex/P) in Patients (pts) with Relapsing Multiple Myeloma (MM).
Authors: Jean-Paul Fermand, Arnaud Jaccard, Margaret Macro, Yurdagul Uzunhan, Christian Allard, Sylvie Castaigne, Marine Divine, Xavier Mariette, Veronique Leblond, Sylvie Chevret
Journal: Blood (2006)
Therapy of relapsed/refractory metastatic triple-negative breast cancer (mTNBC) with an anti-Trop-2-SN-38 antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132): Phase II results.
Authors: Aditya Bardia, Jennifer Robinson Diamond, Wells A. Messersmith, Ingrid A. Mayer, Steven J. Isakoff, Vandana Gupta Abramson, Jordan Berlin, Alexander Starodub, Joyce O'Shaughnessy, Kevin Kalinsky, Rebecca L. Moroose, Nikita C. Shah, Dejan Juric, Geoffrey Shapiro, Michael J. Guarino, Allyson J. Ocean, Francois Wilhelm, Robert M. Sharkey, David M. Goldenberg, Linda T. Vahdat
Journal: Journal of Clinical Oncology (2016)

LBA509 Notice of Retraction: “Therapy of relapsed/refractory metastatic triple-negative breast cancer (mTNBC) with an anti-Trop-2-SN-38 antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132): Phase II results.” ASCO's Confidentiality Policy requires that abstracts be considered confidential and embargoed from the time of submission until the findings have been publicly released in conjunction with the ASCO Annual Meeting. Abstract LBA509, published in the 2016 ASCO Annual Meeting Proceedings Part II, violated this policy and was retracted from publication and presentation at the 2016 ASCO Annual Meeting.
Radiosurgery as primary treatment of metastatic tumors of the spine: Quality of life and adjuvant surgical approach after Cyberknife.
Authors: I. Choi
Journal: Journal of Clinical Oncology (2010)

e19643 Background: Conventional radiotherapy and open surgery only performs a limited role in the treatment of metastatic tumors of the spine The effectiveness of spinal radiosurgery as primary treatment for the spinal metastases was investigated. Methods: From December 2007 to December 2009, a total of 167 patients were treated in the Cyberknife center of the Seoul Wooridul Hospital. Our workload was 347 metastatic tumors (mean 2.07 per patients). Magnetic resonance imaging and PET for tumor response evaluation were taken at intervals of 3-6 months. Quality of life studies were taken at interval of 1-3 months for the Oswestry Disability Index, visual analog scale. Results: The patients age ranges was 25-79 years with mean of 58 years. The most common metastatic tumors were breast cancer (36 cases), lung cancer (34 cases). and hepatoma (16 cases). The prescription dose range 8-40 Gy with a mean of 19.7 Gy. The most common indication for Cyberknife was pain in 92.2%(154/167) of patients. The mean Oswestry Disability Index score before Cyberknife was 24.3, and the mean visual analog scale score was 4.3 before radiosurgry. After Cyberknife, the mean Oswestry Disability Index score was increased up to 25.6. The mean of post-Cyberknife visual analog scale score was down to 3.2. The overall response rate of pain relief was 97%, and the local control rate including stable diseases was seen in 92% after radiosurgery. Multivariate logistic regression modeling found that the Oswestry Disability Index score at presentation was the only independent variable that correlated significantly with survival (p < 0.0001). Adjuvant invasive surgery as like laminectomy, corpectomy and vertebroplasty after Cyberknife was experienced by only 3.8% of tumors. Conclusions: We expect Cyberknife radiosurgery to become a useful palliative and primary treatment of metastatic tumors of the spine. Noninvasive radiosurgery should be considered as the primary treatment modality rather than invasive surgical approach for the spinal metastases. No significant financial relationships to disclose.
Treatment of inflammatory arthritis via targeting of tristetraprolin, a master regulator of pro-inflammatory gene expression
Authors: E A Ross, A J Naylor, J D O'Neil, T Crowley, M L Ridley, J Crowe, T Smallie, T J Tang, J D Turner, L V Norling, S Dominguez, H Perlman, N M Verrills, G Kollias, M P Vitek, A Filer, C D Buckley, J L Dean, A R Clark
Journal: Annals of the Rheumatic Diseases (2016)

Tristetraprolin (TTP), a negative regulator of many pro-inflammatory genes, is strongly expressed in rheumatoid synovial cells. The mitogen-activated protein kinase (MAPK) p38 pathway mediates the inactivation of TTP via phosphorylation of two serine residues. We wished to test the hypothesis that these phosphorylations contribute to the development of inflammatory arthritis, and that, conversely, joint inflammation may be inhibited by promoting the dephosphorylation and activation of TTP. The expression of TTP and its relationship with MAPK p38 activity were examined in non-inflamed and rheumatoid arthritis (RA) synovial tissue. Experimental arthritis was induced in a genetically modified mouse strain, in which endogenous TTP cannot be phosphorylated and inactivated. In vitro and in vivo experiments were performed to test anti-inflammatory effects of compounds that activate the protein phosphatase 2A (PP2A) and promote dephosphorylation of TTP. TTP expression was significantly higher in RA than non-inflamed synovium, detected in macrophages, vascular endothelial cells and some fibroblasts and co-localised with MAPK p38 activation. Substitution of TTP phosphorylation sites conferred dramatic protection against inflammatory arthritis in mice. Two distinct PP2A agonists also reduced inflammation and prevented bone erosion. In vitro anti-inflammatory effects of PP2A agonism were mediated by TTP activation. The phosphorylation state of TTP is a critical determinant of inflammatory responses, and a tractable target for novel anti-inflammatory treatments.
Risk assessment of drug-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a disproportionality analysis using the French Pharmacovigilance Database
Authors: M.S. Agier, N. Boivin, A. Maruani, B. Giraudeau, A. Gouraud, F. Haramburu, M.J. Jean Pastor, L. Machet, A.P. Jonville-Bera
Journal: British Journal of Dermatology (2016)
Sunitinib in combination with docetaxel and prednisone in patients (pts) with metastatic hormone-refractory prostate cancer (mHRPC)
Authors: A. J. Zurita, G. Liu, T. Hutson, M. Kozloff, N. Shore, G. Wilding, C. J. Logothetis, I. Chen, E. Chow Maneval, D. George
Journal: Journal of Clinical Oncology (2009)

5166 Background: Overexpression of VEGF and PDGF has been implicated in prostate cancer progression and bone metastases. Sunitinib is an oral, multitargeted inhibitor of VEGFRs, PDGFRs, and other tyrosine kinases which may improve the efficacy of chemotherapy in pts with mHRPC. We performed a multicenter phase I/II study of sunitinib in combination with docetaxel and prednisone as first-line therapy in pts with mHRPC. The combination dose was established in phase I (Zurita et al, ECCO. 2007). Final results from phase II will be reported. Methods: Pts received treatment in a 21-day cycle: sunitinib 37.5 mg/d on days 1–14, docetaxel 75 mg/m 2 on day 1, and prednisone 5 mg BID on days 1–21. Dose reductions were permitted for treatment-related toxicity. The primary endpoint was PSA response rate (PSA Working Group Criteria). Secondary endpoints included tumor response rate (RECIST), safety and patient-reported outcomes. Results: Fifty-five pts were enrolled and 13 remained on study at the time of the data cutoff (1 Oct 08). Thirty-six discontinued from the study due to disease progression (16), adverse events (AEs; 13), consent withdrawal (6) and other (1). Six pts completed the study (16 cycles) and continued treatment on another protocol. Pts received a median of 23 weeks of therapy (range, 2–84). The most common treatment-related grade 3–4 AEs were neutropenia (75%), febrile neutropenia (15%), fatigue (15%), stomatitis (7%), and anorexia (7%). Sunitinib dose reduction to 25 mg/d was required in 14 pts (26%), and 3 pts (6%) had a further dose reduction to 12.5 mg/d. Docetaxel dose reduction to 60 mg/m 2 was required in 18 pts (33%). PSA responses occurred in 31 pts (56%), with a preliminary median time to PSA progression of 42.1 weeks. Out of 33 pts with measurable disease, thirteen (39%) had a confirmed partial response (PR) and another 7 (21%) had an initial PR. The median progression-free and overall survivals have not been reached, but the probability of survival at 48 weeks is 92.4% (95% CI: 77.5, 97.6). Patient-reported assessments of pain and quality of life will be reported. Conclusions: Sunitinib in combination with docetaxel and prednisone is tolerated and has antitumor activity in pts with mHRPC, as indicated by both PSA and RECIST-defined tumor responses. [Table: see text]
The PARP Inhibitor AZD2461 Provides Insights into the Role of PARP3 Inhibition for Both Synthetic Lethality and Tolerability with Chemotherapy in Preclinical Models
Authors: Lenka Oplustil O'Connor, Stuart L. Rulten, Aaron N. Cranston, Rajesh Odedra, Henry Brown, Janneke E. Jaspers, Louise Jones, Charlotte Knights, Bastiaan Evers, Attilla Ting, Robert H. Bradbury, Marina Pajic, Sven Rottenberg, Jos Jonkers, David Rudge, Niall M.B. Martin, Keith W. Caldecott, Alan Lau, Mark J. O'Connor
Journal: Cancer Research (2016)

The PARP inhibitor AZD2461 was developed as a next-generation agent following olaparib, the first PARP inhibitor approved for cancer therapy. In BRCA1-deficient mouse models, olaparib resistance predominantly involves overexpression of P-glycoprotein, so AZD2461 was developed as a poor substrate for drug transporters. Here we demonstrate the efficacy of this compound against olaparib-resistant tumors that overexpress P-glycoprotein. In addition, AZD2461 was better tolerated in combination with chemotherapy than olaparib in mice, which suggests that AZD2461 could have significant advantages over olaparib in the clinic. However, this superior toxicity profile did not extend to rats. Investigations of this difference revealed a differential PARP3 inhibitory activity for each compound and a higher level of PARP3 expression in bone marrow cells from mice as compared with rats and humans. Our findings have implications for the use of mouse models to assess bone marrow toxicity for DNA-damaging agents and inhibitors of the DNA damage response. Finally, structural modeling of the PARP3-active site with different PARP inhibitors also highlights the potential to develop compounds with different PARP family member specificity profiles for optimal antitumor activity and tolerability. Cancer Res; 76(20); 6084-94. ©2016 AACR.
Critical Care Medicine
Authors: Michael A. Matthay
Journal: JAMA (1991)

Considerable basic and clinical research has been devoted to understanding the natural history, pathophysiology, and pathogenesis of acute lung injury. Several neutrophil-dependent and neutrophil-independent mechanisms are probably important in mediating the initial phase of acute lung injury.<sup>1,2</sup>The injury involves the airways, the interstitium, and the pleural spaces as well as the endothelial and the epithelial barriers of the lung.<sup>1,2</sup>The original description of acute lung injury (also known as the adult respiratory distress syndrome) emphasized that it is a clinical syndrome of acute respiratory failure with bilateral roentgenographic infiltrates from both atelectasis and noncardiogenic pulmonary edema.<sup>3</sup>Although this initial description was useful, it became apparent that an expanded definition was needed to achieve better precision in identifying the mechanisms responsible for acute lung injury and to determine the prognosis for survival. An expanded definition has, therefore, been developed that includes a proposed semiquantitative scoring
Pre-Transplant Weight Loss and Total Serum Protein Predict Relapse Of Acute Myeloid Leukaemia After Allogeneic Stem Cell Transplantation
Authors: Thomas Luft, Sascha Dietrich, Aleksandar Radujkovic, Friedrich Stölzel, Christine Falk, Axel Benner, Markus Schaich, Martin Bornhäuser, Gerhard Ehninger, Alwin Kraemer, Ute Hegenbart, Anthony D Ho, Peter Dreger
Journal: Blood (2013)
Gay, bisexual, and other men who have sex with men: time to end the fixation with HIV
Authors: M Pakianathan, N Daley, A Hegazi
Journal: BMJ (2016)

Attention must shift to broader inequalities in health and wellbeing 

HIV has been inextricably linked with gay men’s health since the term “gay related immune deficiency” was first used to refer to AIDS in the early 1980s. Today, the collective emphasis of health interventions targeted at gay, bisexual, and other men who have sex with men remains focused on preventing sexually transmitted infection, to the extent that absence of HIV has come to be regarded almost synonymously with gay men’s health.

Beyond HIV, health disparities in this group of men encompass a range of physical conditions, including asthma, cardiovascular disease, and cancer.1 They are also more likely to experience physical disability and to report poorer self rated health.1 Determinants of these differences have received limited public and medical attention and remain relatively unstudied. Further inequality is driven by an unwillingness to seek medical care or disclose sexuality to healthcare providers because of perceived negative healthcare experiences.2 Demographic and socioeconomic factors also contribute independently to health disparities within this diverse population.3 …
A single institution’s experience with the value of FDG-PET-CT imaging in patients with newly diagnosed stage IIB-IIIB breast cancer.
Authors: Gary Schnur, Katherine Glass, Chad W Cummings, Alberto J. Montero, Jame Abraham, Halle C. F. Moore, G. Thomas Budd
Journal: Journal of Clinical Oncology (2016)

123 Background: The Cleveland Clinic is utilizing disease specific teams to craft care paths for value based disease management. The report by Groheux (JNCI 2012; 104:1879-1887), reported 18 FDG-PET-CT detected distant metastasis in 10.7, 17.5 and 36.5% of stage IIB- IIIB breast cancer patients. Based on this report, the breast team incorporated 18 FDG-PET- CT imaging for initial staging of IIB-IIIB patients. Methods: Treatment algorithms were developed by a multi-disciplinary breast cancer team. The content was reviewed by stakeholders throughout the health system, and feedback was incorporated into the care paths as appropriate. Content was communicated using physician meetings, electronic communication, tumor boards, and operational pilots. The treatment algorithm, along with the supporting narrative, was placed on the cancer center intranet, accessible to all practicing physicians. Additional intranet analysis was performed using Google Analytics, which identifies the site location and frequency of document downloads. We retrospectively examined the impact of this posting after one year (7/2014-7/2015). Manual chart review identified new patient consults for Stage IIB-IIIB breast cancer at our main campus and highest volume regional sites. Results: PET scans were ordered in 36 stage IIB, 19 stage IIIA, and 3 stage IIIB patients. Of the 36 IIB patients scanned, occult metastatic disease was noted in 1, and 2 patients migrated to IIIA without a change in treatment. 19 IIIA patients had no change in stage, although an asymptomatic second primary lung cancer was discovered in 1 .Three stage IIIB patients were without staging change. Conclusions: PET/CT imaging did not contribute to patient management for stage IIB-IIIB breast cancer patients at our institution, unlike the results reported elsewhere. Analysis of care path metrics allows us to expediently review and adjust recommendations to affiliated physicians.
Body Mass Index and All-Cause Mortality
Authors: Shilpa N. Bhupathiraju, Walter C. Willett, Frank B. Hu
Journal: JAMA (2016)

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Outcomes After Double Unit Unrelated Cord Blood Transplantation (UCBT) Compared with Single UCBT In Adults with Acute Leukemia In Remission. An Eurocord and ALWP Collaboration Study
Authors: Vanderson Rocha, Myriam Labopin, Mohamad Mohty, Guillermo F Sanz, Bernard Rio, Sabine Furst, Anne Sirvent, Gérard Socié, Reza Tabrizzi, Ibrahim Yakoubagha, Eric Deconinck, Jan J. Cornelissen, William Arcese, Josep-Maria Ribera, E. Nikiforakis, Mauricette Michallet, Alessandro Crotta, Annalisa Ruggeri, Eliane Gluckman
Journal: Blood (2010)
Phase II Trial and Correlative Genomic Analysis of Everolimus Plus Bevacizumab in Advanced Non–Clear Cell Renal Cell Carcinoma
Authors: Martin H. Voss, Ana M. Molina, Ying-Bei Chen, Kaitlin M. Woo, Joshua L. Chaim, Devyn T. Coskey, Almedina Redzematovic, Patricia Wang, William Lee, S. Duygu Selcuklu, Chung-Han Lee, Michael F. Berger, Satish K. Tickoo, Victor E. Reuter, Sujata Patil, James J. Hsieh, Robert J. Motzer, Darren R. Feldman
Journal: Journal of Clinical Oncology (2016)

Purpose The decreased effectiveness of single-agent targeted therapies in advanced non-clear cell renal cell carcinoma (ncRCC) compared with clear cell renal cell carcinoma (RCC) supports the study of combination regimens. We evaluated the efficacy of everolimus plus bevacizumab in patients with metastatic ncRCC. Patients and Methods In this single-center phase II trial, treatment-naive patients received everolimus 10 mg oral once per day plus bevacizumab 10 mg/kg intravenously every 2 weeks. The primary end point was progression-free survival (PFS) at 6 months. Correlative analyses explored candidate tissue biomarkers through next-generation sequencing. Results Thirty-five patients were enrolled with the following histologic subtypes: chromophobe (n = 5), papillary (n = 5), and medullary (n = 2) RCC and unclassified RCC (uRCC, n = 23). The majority of patients had papillary growth as a major component (n = 14). For 34 evaluable patients, median PFS, overall survival, and objective response rate (ORR) were 11.0 months, 18.5 months, and 29%, respectively. PFS varied by histology ( P < .001), and ORR was higher in patients with significant papillary (seven of 18) or chromophobe (two of five) elements than for others (one of 11). Presence of papillary features were associated with benefit, including uRCC, where it correlated with ORR (43% v 11%), median PFS (12.9 v 1.9 months), and overall survival (28.2 v 9.3 months; P < .001). Several genetic alterations seemed to segregate by histology. In particular, somatic mutations in ARID1A were seen in five of 14 patients with papillary features but not in other RCC variants. All five patients achieved treatment benefit. Conclusion The study suggests efficacy for this combination in patients with ncRCC characterized by papillary features. Distinct mutational profiles among ncRCCs vary according to specific histology.
Addition of a non-immersive virtual reality component to treadmill training to reduce fall risk in older adults (V-TIME): a randomised controlled trial
Authors: Anat Mirelman, Lynn Rochester, Inbal Maidan, Silvia Del Din, Lisa Alcock, Freek Nieuwhof, Marcel Olde Rikkert, Bastiaan R Bloem, Elisa Pelosin, Laura Avanzino, Giovanni Abbruzzese, Kim Dockx, Esther Bekkers, Nir Giladi, Alice Nieuwboer, Jeffrey M Hausdorff
Journal: The Lancet (2016)
SU11657, a FLT3-Targeted Tyrosine Kinase, Has Pro-Apoptotic Activity on Leukemia Cells In Vitro.
Authors: Tiziana Grafone, Laura Ferraretti, Emanuela Ottaviani, Manuela Mancini, Michela Palmisano, Michele Malagola, Carolina Terragna, Matteo Renzulli, Angela Poerio, Marilina Amabile, Simona Soverini, Sabrina Colarossi, Ilaria Iacobucci, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2005)