tbuckley/cabot-search huggingface dataset:
Neoadjuvant endocrine therapy for resectable breast cancer: A systematic review and meta-analysis.
Authors: Frederico Leal, Vitor Teixeira Liutti, Vivian Antunes Santos, Maximiliano Augusto Novis de Figueiredo, Ligia Traldi Macedo, Jose A. Rinck, Andre Deeke Sasse
Journal: Journal of Clinical Oncology (2014)

e11508 Background: The role of neoadjuvant chemotherapy (nCT) for women with high-risk breast cancer is well established. Nevertheless, endocrine therapy is much less recommended despite encouraging results obtained in the metastatic and adjuvant settings. This systematic review aims to evaluate existing evidence on neoadjuvant hormone therapy (nHT) for breast cancer. Methods: A systematic search on electronic databases was performed. Studies reporting results from prospective, randomized trials were included if comparing: nHT versus no treatment or; nHT versus nCT or; nHT plus CT versus nCT alone or; nHT plus CT versus nHT alone or; nHT versus other nHT regimen. The endpoints of interest were overall response rate (ORR, from clinical and imaging perspectives) and toxicity. Pooled data from trials within a same comparison were calculated and assessed through RevMan 5.1 software and are expressed as OR with respective 95% confidence intervals. Results: Nine studies met the inclusion criteria. Five of them compared nHT with tamoxifen versus nHT with aromatase inhibitors (AI). Meta-analysis demonstrated superiority of AIs in ORR assessed by ultrasonography (OR 1.54; 95% CI 1.18 – 2.00) with no significant increase in toxicity. Two trials compared nHT against nCT, with no statistically significant difference between them (OR for ORR 0.75; 95% CI 0.35 - 1.6). Also, when only postmenopausal women were considered, no difference was detected (OR for ORR 1.01; 95% CI 0.62 - 1.63). One trial compared nHT plus CT versus no neoadjuvant treatment, and obtained an 83% overall response rate (ORR). One trial compared nHT plus CT versus nCT alone and found a non-significant increase in ORR for adding hormone blockade to nCT (OR 1.48; 95% CI 0.58 - 3.77). No trial compared nHT plus CT versus nHT alone. Conclusions: Neoadjuvant endocrine therapy is a safe and feasible option, but it cannot yet be considered similar to chemotherapy, which remains the standard treatment. The role of nHT should be better investigated in postmenopausal women, as ORR results seem equivalent to those obtained with nCT. Due to higher response rates, aromatase inhibitors are preferable over tamoxifen as nHT.
Abstract 18551: Predisposing Factors of Persistent Symptoms of Depression and Anxiety Among Patients With Acute Coronary Syndrome
Authors: Abdullah Alhurani, Terry Lennie, Debra Moser
Journal: Circulation (2015)

Introduction: Depression and anxiety are highly prevalent in patients with acute coronary syndrome (ACS) contributing to poor health outcomes such as mortality and rehospitalization Several studies have also demonstrated a relationship between depression and anxiety and cardiac events in patients with ACS. However, substantial morbidities arise from those patients who persistently suffer from these disorders. Objective: The primary objective of this study was to determine the predisposing factors of persistent symptoms of depression and anxiety among patients with ACS. Methods: A total of 1199 patients participated from five hospitals in Dublin, Ireland. Logistic regression analyses were used to determine the predisposing factors of persistent symptoms of depression and anxiety. Predisposing factors included age, gender, body mass index, education level, marital status, smoking history, and diabetes history, history of coronary bypass graft (CABG), stroke, or ACS, baseline knowledge, attitudes and beliefs. We also controlled for baseline anxiety when investigating persistent depression and for baseline depression when investigating persistent anxiety. Patients who been depressed or anxious at baseline and three months follow-up were considered to have persistent depression or anxiety. Results: Older age (β 0.98; 95% CI: 0.96 - 1.00; p = 0.040), female gender (β 1.99; 95% CI: 1.30 - 3.05; p = 0.002), history of CABG (β 2.10; 95% CI: 1.18 - 3.71; p = 0.011), history of non ST elevation myocardial infarction compared to other ACS (β 1.78; 95% CI: 1.04 - 3.06; p = 0.037), and baseline anxiety (β 1.40; 95% CI: 1.25 - 1.57; p &lt;0.001) were significant predictors of persistent depression. Furthermore, older age (β 0.98; 95% CI: 0.96 - 1.00; p = 0.030), female gender (β 1.98; 95% CI: 1.22 - 3.20; p = 0.005), and baseline depression (β 1.24; 95% CI: 1.14 - 1.36; p &lt;0.001) were significant predictors of persistent anxiety. Conclusions: Health care providers need to take in consideration the predisposing factors of persistent depression and anxiety to pre-intervene and prevent morbidities associated with these disorders.
HIV Incidence Among Young Men Who Have Sex With Men—Seven US Cities, 1994-2000
Journal: JAMA (2001)

Twenty years ago, on June 5, 1981, MMWR published a report of five cases of Pneumocystis carinii pneumonia (PCP) among previously healthy young men in Los Angeles (1 ).All of the men were described as "homosexuals"; two had died.Local clinicians and the Epidemic Intelligence Service (EIS) Officer stationed at the Los Angeles County Department of Public Health, prepared the report and submitted it for MMWR publication in early May 1981.Before publication, MMWR editorial staff sent the submission to CDC experts in parasitic and sexually transmitted diseases.The editorial note that accompanied the published report stated that the case histories suggested a "cellular-immune dysfunction related to a common exposure" and a "disease acquired through sexual contact."The report prompted additional case reports from New York City, San Francisco, and other cities.At about the same time, CDC's investigation drug unit, the sole distributor of pentamidine, the therapy for PCP, began to receive requests for the drug from physicians also to treat young men.In June 1981, CDC developed an investigative team to identify risk factors and to develop a case definition for national surveillance.Within 18 months, epidemiologists conducted studies and prepared MMWR reports that identified all of the major risks factors for acquired immnodeficiency syndrome (AIDS).In March 1983, CDC issued recommendations for prevention of sexual, drug-related, and occupational transmission based on these early epidemiologic studies and before the cause of the new, unexplained illness was known.MMWR has published more than 400 reports about human immunodeficiency virus (HIV) and AIDS and remains a primary source of information about the epidemiology, surveillance, prevention, care, and treatment of HIV and AIDS.This anniversary issue provides new reports on the epidemiologic features and impact of HIV/ AIDS on communities in the United States and in other countries.A compilation of notable MMWR reports on HIV and AIDS is available at http://www.cdc.gov/mmwr/hiv_aids20.html.A video that includes interviews with participants in these first AIDS investigations and reports and a video summary of each report in this issue is available at http://www.cdc.gov/mmwr.
Isotretinoin and Timing of Procedural Interventions
Authors: Leah K. Spring, Andrew C. Krakowski, Murad Alam, Ashish Bhatia, Jeremy Brauer, Joel Cohen, James Q. Del Rosso, Lucia Diaz, Jeffrey Dover, Lawrence F. Eichenfield, Geoffrey C. Gurtner, C. William Hanke, Marla N. Jahnke, Kristen M. Kelly, Shilpi Khetarpal, Megan A. Kinney, Moise L. Levy, James Leyden, Michael T. Longaker, Girish S. Munavalli, David M. Ozog, Heidi Prather, Peter R. Shumaker, Elizabeth Tanzi, Abel Torres, Mara Weinstein Velez, Abigail B. Waldman, Albert C. Yan, Andrea L. Zaenglein
Journal: JAMA Dermatology (2017)

<h3>Importance</h3> The notion that systemic isotretinoin taken within 6 to 12 months of cutaneous surgery contributes to abnormal scarring or delayed wound healing is widely taught and practiced; however, it is based on 3 small case series from the mid-1980s. <h3>Objective</h3> To evaluate the body of literature to provide evidence-based recommendations regarding the safety of procedural interventions performed either concurrently with, or immediately following the cessation of systemic isotretinoin therapy. <h3>Evidence Review</h3> A panel of national experts in pediatric dermatology, procedural/cosmetic dermatology, plastic surgery, scars, wound healing, acne, and isotretinoin was convened. A systematic PubMed review of English-language articles published from 1982 to 2017 was performed using the following search terms: isotretinoin, 13-cis-retinoic acid, Accutane, retinoids, acitretin, surgery, surgical, laser, ablative laser, nonablative laser, laser hair removal, chemical peel, dermabrasion, wound healing, safety, scarring, hypertrophic scar, and keloid. Evidence was graded, and expert consensus was obtained. <h3>Findings</h3> Thirty-two relevant publications reported 1485 procedures. There was insufficient evidence to support delaying manual dermabrasion, superficial chemical peels, cutaneous surgery, laser hair removal, and fractional ablative and nonablative laser procedures for patients currently receiving or having recently completed isotretinoin therapy. Based on the available literature, mechanical dermabrasion and fully ablative laser are not recommended in the setting of systemic isotretinoin treatment. <h3>Conclusions and Relevance</h3> Physicians and patients may have an evidence-based discussion regarding the known risk of cutaneous surgical procedures in the setting of systemic isotretinoin therapy. For some patients and some conditions, an informed decision may lead to earlier and potentially more effective interventions.
Epigenetically Aberrant Stroma in MDS Propagates Disease via Wnt/β-Catenin Activation
Authors: Tushar D. Bhagat, Si Chen, Matthias Bartenstein, A. Trevor Barlowe, Dagny Von Ahrens, Gaurav S. Choudhary, Patrick Tivnan, Elianna Amin, A. Mario Marcondes, Mathijs A. Sanders, Remco M. Hoogenboezem, Suman Kambhampati, Nandini Ramachandra, Iaonnis Mantzaris, Vineeth Sukrithan, Remi Laurence, Robert Lopez, Prafulla Bhagat, Orsi Giricz, Davendra Sohal, Amittha Wickrema, Cecilia Yeung, Kira Gritsman, Peter Aplan, Konrad Hochedlinger, Yiting Yu, Kith Pradhan, Jinghang Zhang, John M. Greally, Siddhartha Mukherjee, Andrea Pellagatti, Jacqueline Boultwood, Britta Will, Ulrich Steidl, Marc H.G.P. Raaijmakers, H. Joachim Deeg, Michael G. Kharas, Amit Verma
Journal: Cancer Research (2017)

Abstract The bone marrow microenvironment influences malignant hematopoiesis, but how it promotes leukemogenesis has not been elucidated. In addition, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow–derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands. Stroma derived from 5-azacytidine–treated patients lacked aberrant methylation and DNMTi treatment of primary MDS stroma enhanced its ability to support erythroid differentiation. An integrative expression analysis revealed that the WNT pathway antagonist FRZB was aberrantly hypermethylated and underexpressed in MDS stroma. This result was confirmed in an independent set of sorted, primary MDS-derived mesenchymal cells. We documented a WNT/β-catenin activation signature in CD34+ cells from advanced cases of MDS, where it associated with adverse prognosis. Constitutive activation of β-catenin in hematopoietic cells yielded lethal myeloid disease in a NUP98–HOXD13 mouse model of MDS, confirming its role in disease progression. Our results define novel epigenetic changes in the bone marrow microenvironment, which lead to β-catenin activation and disease progression of MDS. Cancer Res; 77(18); 4846–57. ©2017 AACR.
The Pralatrexate - Romidepsin Doublet: A Well Tolerated and Highly Effective Combination for Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma
Authors: Jennifer E Amengual, Renee Lichtenstein, Celeste Rojas, Ahmed Sawas, Changchun Deng, Emily Lichtenstien, Karen Kahn, Jennifer Kimberly Lue, Yuxuan Liu, Changhong Qiao, Renu Nandakumar, Serge Cremers, Owen A. O'Connor
Journal: Blood (2016)
Similar Efficacy of Dasatinib and Nilotinib As Second-Line Therapy in Patients with Chronic Phase Chronic Myeloid Leukemia Failing Imatinib: A Retrospective, Real-Life Study
Authors: Mario Tiribelli, Massimiliano Bonifacio, Gianni Binotto, Alessandra Iurlo, Francesca Cibien, Elena Maino, Anna Guella, Gianluca Festini, Claudia Minotto, Ercole De Biasi, Federico De Marchi, Luigi Scaffidi, Luca Frison, Cristina Bucelli, Marta Medeot, Elisabetta Calistri, Mauro Krampera, Filippo Gherlinzoni, Gianpietro Semenzato, Achille Ambrosetti, Giovanni Pizzolo, Renato Fanin
Journal: Blood (2016)
Targeted therapy for HER2 driven colorectal cancer.
Authors: Jeffrey S. Ross, Siraj Mahamed Ali, Julia Andrea Elvin, Alexa Betzig Schrock, James Suh, Jo-Anne Vergilio, Shakti Ramkissoon, Eric Allan Severson, Sugganth Daniel, David Fabrizio, Garrett Michael Frampton, Vincent A. Miller, Philip J. Stephens, Laurie M. Gay
Journal: Journal of Clinical Oncology (2017)

3583 Background: ERBB2 ( HER2) genomic alterations (GA) are evolving therapy taregets in metastatc coorectal cancer (mCRC). Methods: Hybrid capture based comprehensive genomic profiling (CGP) was performed on 8874 (9.6%) mCRC including both colonic adenocarcinomas (7587 cases; 85%) and rectal adenocarcinomas (1287 cases, 15%) Tumor mutational burden (TMB) was calculated from a minimum of 1.2 Mb of sequenced DNA. Results: ERBB2 amplifications or a short variant (SV) alterations or both were found in 433 (4.9%) of the total mCRC. 195 (45%) of the ERBB2 positive mCRC were female and 238 (55%) were male. Median age was 54 years (range 22 to 88 years). The most frequently co-altered genes were SV GA in TP53 (82%), APC (70%), KRAS (26%), SMAD4 (15%) and PIK3CA (13%). Clinically relevant GA significantly under-represented in ERBB2-altered CRC included significantly reduced GA in KRAS at 26% (p = 0.001) and BRAF at 4% (p = 0.003) as well as other kinases at 1% including EGFR, KIT, MET and RET. The frequency of TMB at &gt; 10 mut/Mb (p &lt; 0.0001), but at &gt; 20 mut/Mb mCRC cases demonstrated virtually the same results regardless to ERBB2 status at a frequency of x%. The overall ERBB2 GA frequency at 5.3% in rectal mCRC is slightly higher than that seen in colonic mCRC at 4.9%, (p = 0.36). The frequency of TMB &gt; 10 mut/Mb in ERBB2 WT mCRC is greater in the colonic mCRC than the rectal mCRC (p &lt; 0.0001 for both comparisons). When &gt; 20 mut/Mb is used as the cut-off, the greater frequency of TMB in colonic mCRC versus rectal mCRC remains significant (p &lt; 0.0001). When the ERBB2altered mCRC cases are evaluated, the greater frequency of TMB &gt; 10 mu/Mb in colonic mCRC versus rectal mCRC remains significant (p = 0.009), but the greater frequency in colonic verses rectal mCRC at the &gt; 20 mut/Mb is not significant (p = 0.37). Conclusions: Although lower than observed in breast and upper gastrointestinal carcinomas where anti-HER2 therapies are approved indications, the frequency of ERBB2 GA in CRC at 4.9% is significant. Importantly, nearly half of CRC ERBB2 alterations are SVs, not detectable by routine IHC and FISH testing. However, the success of anti-HER2 therapies shown here and progress in on-going clinical trials indicates that targeting ERBB2 has potential to become an approved advance in precision therapy for mCRC patients.
Factors associated with early mortality in metastatic breast cancer (MBC) in a population based cohort.
Authors: Ines Maria Vaz Duarte Luis, Nancy U. Lin, Nancy Lynn Keating, Joyce Lii, William Thomas Barry, Eric P. Winer, Rachel A. Freedman
Journal: Journal of Clinical Oncology (2015)

1577 Background: Significant improvements in survival time have been achieved for patients (pts) with MBC. Nevertheless, some still die soon after diagnosis. Data regarding features associated with early death are limited. Methods: Using Surveillance, Epidemiology, and End Results data, we studied 4,032 pts with de novo MBC diagnosed between 01/2010- 06/2011(when Human Epidermal Growth Factor Receptor 2 [HER2] status started to be recorded) with follow up of at least 6 months. Multivariate logistic regression models assessed features associated with death within 1 and 6 months of diagnosis, adjusting for the variables in the table. Results: The median age was 61 (22-99), 75% were white, 93% were insured. Disease subgroups were the following: hormone receptor (HR)+HER2- (61%); HR+HER2+(15%); HR-HER2+ (9%) and triple negative (15%). Approximately 8% died by 1 month and 20% died by 6 months. Older age, lack of insurance, and triple negative subtype were associated with early death. SeeTable. Conclusions: Among a population based cohort, one fifth died within 6 months. This study highlights that both clinical factors and insurance type seem to impact early death. These data suggest the importance of studying how differences in insurance reform and other disease characteristics may modify risk for early death and may also inform interventions aimed at those at risk for early death. % Death within 1 month (row) Adj OR (95%CI) % Death within 6 months (row) Adj OR(95%CI) Age ≤40 2 1 6 1 40-49 4 2.6 (1.1-6.4) 10 2.1 (1.3-3.4) 50-59 6 4.0 (1.9-8.4) 17 3.7 (2.4-5.5) 60-69 8 5.9 (2.7-12.8) 20 4.8 (3.2-7.1) ≥70 13 10.6 (5.7-19.7) 30 8.5 (5.5-13.1) Marital status Married 6 1.0 15 1.0 Single 10 1.3 (0.9-1.8) 23 1.3 (1.0-1.5) Insurance Insured 8 1 17 1 Medicaid 8 1.4 (1.1-1.8) 21 1.4 (1.1-1.9) Uninsured 16 3.1 (2.3-4.2) 27 2.2. (1.6-3.1) Unknown (UK) 6 0.7 (0.4-1.5) 24 1.6 (0.8-3.0) Site Distant lymph node 2 1 7 1.0 Distant metastases 8 4.3 (1.9-9.7) 21 3.7 (2.3-5.9) Local extension 4 1.6 (0.5-4.4) 12 1.4 (0.7-2.8) UK 11 5.6 (2.0-15.5) 21 3.6 (1.8-7.0) Subtype HR+HER2- 8 1 17 1 HR+HER2+ 8 1.3 (0.9-1.9) 22 1.2 (1.1-1.4) HR-HER2+ 7 1.4 (0.9-2.2) 16 1.8 (1.2-2.7) HR-HER2- 12 2.0 (1.7-2.4) 35 3.1 (2.5-3.8) Total (N,%) 326 (8) 792 (20) by race, registry, grade, histology.
Rapid Infusion of Rituximab Is Well Tolerated in Children with Hematologic, Oncologic, and Rheumatologic Disorders
Authors: Amanda Bell Grimes, Marietta M DeGuzman, Jessica Poehls, Taylor Olmsted, Rachel Beaty Carroll, Michele S Redell, Susan E. Kirk, Charles G Minard, Melanie Brooke Bernhardt, Jenny M. Despotovic
Journal: Blood (2016)
Cardiovascular Toxicity after Therapy for Diffuse Large B Cell Lymphoma Occurs Early and Results in Decreased Overall Survival.
Authors: Sabarish Ram Ayyappan, Akiva Diamond, Vinita Gupta, Brenda Cooper, Ben K. Tomlinson, Ehsan Malek, Leland Metheny, Hillard M. Lazarus, Stanton L. Gerson, Marcos De Lima, Paolo F. Caimi
Journal: Blood (2016)
Immune gene signatures in triple-negative breast cancers characterized by varying levels of chromosomal instability.
Authors: Balazs Gyorffy, Giulia Bottai, Adam Nagy, Lajos Pusztai, Libero Santarpia
Journal: Journal of Clinical Oncology (2017)

1096 Background: Triple-negative breast cancer (TNBC) is generally characterized by high levels of chromosomal instability (CIN) and an intense immune infiltration. However, the link between these two hallmarks and its implications for clinical practice has not been fully elucidated. Methods: We generated eight immune metagenes representing various immune components: natural killer [NK], dendritic cells [DC], T-cells [TC], B-cells [BC], cytotoxic T-cells [CT], interferon [IFN], nuclear factor-κB [NF-kB], and macrophages [M]. Publicly available gene expression data from forty-two data sets, including 862 TNBC samples, were collected. TNBC tumors were clustered in three main subgroups (Basal-Like [BL1/2], Immunomodulatory [IM], and Mesenchymal/Mesenchymal Stem-Like [MS]) using transcriptomic profiling. The CIN70 signature was used to stratify TNBC patients according to the levels of CIN. Statistical analyses were performed using Mann–Whitney U test and Kaplan-Meier analyses. Results: The majority of TNBC samples showed a high level of CIN (83%), and several immune modules were differentially expressed between CIN-high and CIN-low tumors. Specifically, CT, NK, DC, M, and NF-kB signatures were overexpressed in CIN-low TNBC ( p &lt; 1.0E-04). We then evaluated the distribution of genomic instability among TNBC molecular subgroups. Noteworthy, the CIN-high group was composed by a comparable proportion of BL1/2 (39%) and MS (35%) tumors, while CIN-low TNBCs were consistently enriched for MS cancers (61%). Higher expression of the NK, M, and IFN metagenes lead to better survival in CIN-high tumors ( p = 1.9E-02, p = 2.1E-04, and p = 1.1E-03, respectively). Only IFN had the same correlation to survival in CIN-low ( p = 1.4E-02). Conclusions: TNBCs with low levels of CIN may principally enclose M/MSL tumors, which are characterized by an intense immune infiltration and overall good prognosis. Conversely, the TNBC CIN-high group is more heterogeneous in terms of both biological features and levels of immune infiltrates. Therapeutic strategies to promote and boost immune response in the genomically unstable TNBC subgroup warrant further investigation.
Socio-demographic variations in lung cancer screening before and after USPSTF recommendation: Results from national health interview surveys (NHIS).
Authors: Qian Wang, Changchuan Jiang, Lei Deng, Yaning Zhang, Gabriel Albert Sara
Journal: Journal of Clinical Oncology (2017)

1563 Background: In 2013, USPSTF recommended low-dose CT screening (LCS) for lung cancer in high-risk adults. The change in real-world practice is largely unknown, as well as the association with socio-demographic factors. Methods: Data were extracted from the population-based 2010 and 2015 NHIS. LCS was defined as a chest CT to check for lung cancer within the past year. We included adults aged 55 to 80 years who 1) have 30+ pack-year smoking history; 2) are currently smokers or have quitted within the past 15 years. We excluded adults who 1) have lung cancer; 2) had not seen a physician in the past year. We used weighted analyses to estimate national lung cancer screening rates. Results: A total of 874 and 1041 high-risk smokers responded to the LCS questions for lung cancer in 2010 and 2015, respectively. The screening rate more than doubled from 4.1% to 9.1% (P &lt; 0.01) in all respondents. The increase was greater in women (2.9% to 9.5%, p &lt; 0.01) than men (5.2% to 8.8%, p = 0.03) and in age 65-80 (4.7% to 12.3%, p &lt; 0.01) than age 55-64 (3.8% to 6.3%, p = 0.16). White saw the largest increase and highest rate in 2015 (4.0% to 9.3%, p = &lt; 0.01). Those with some college or above education had the highest rate in 2010, but the lowest in 2015. Household income above 75,000 dollars was associated with the lowest rate in both 2010 and 2015. Conclusions: Since the recommendation of USPSTF, LCS rate for lung cancer has doubled but remains less than 10%. Higher education and household income are associated with lower screening rate, in contrast to studies of other cancers. [Table: see text]