tbuckley/cabot-search huggingface dataset:
Immune Escape in Breast Cancer During<i>In Situ</i>to Invasive Carcinoma Transition
Authors: Carlos R. Gil Del Alcazar, Sung Jin Huh, Muhammad B. Ekram, Anne Trinh, Lin L. Liu, Francisco Beca, Xiaoyuan Zi, Minsuk Kwak, Helga Bergholtz, Ying Su, Lina Ding, Hege G. Russnes, Andrea L. Richardson, Kirsten Babski, Elizabeth Min Hui Kim, Charles H. McDonnell, Jon Wagner, Ron Rowberry, Gordon J. Freeman, Deborah Dillon, Therese Sorlie, Lisa M. Coussens, Judy E. Garber, Rong Fan, Kristie Bobolis, D. Craig Allred, Joon Jeong, So Yeon Park, Franziska Michor, Kornelia Polyak
Journal: Cancer Discovery (2017)

Abstract To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45+CD3+ T cells demonstrated a decrease in CD8+ signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB+CD8+ T cells in IDC than in DCIS, including in matched DCIS and recurrent IDC. T-cell receptor clonotype diversity was significantly higher in DCIS than in IDCs. Immune checkpoint protein TIGIT-expressing T cells were more frequent in DCIS, whereas high PD-L1 expression and amplification of CD274 (encoding PD-L1) was only detected in triple-negative IDCs. Coamplification of a 17q12 chemokine cluster with ERBB2 subdivided HER2+ breast tumors into immunologically and clinically distinct subtypes. Our results show coevolution of cancer cells and the immune microenvironment during tumor progression. Significance: The design of effective cancer immunotherapies requires the understanding of mechanisms underlying immune escape during tumor progression. Here we demonstrate a switch to a less active tumor immune environment during the in situ to invasive breast carcinoma transition, and identify immune regulators and genomic alterations that shape tumor evolution. Cancer Discov; 7(10); 1098–115. ©2017 AACR. See related commentary by Speiser and Verdeil, p. 1062. This article is highlighted in the In This Issue feature, p. 1047
Risk of Acute Myocardial Infarction After the Death of a Significant Person in One's Life
Authors: Elizabeth Mostofsky, Malcolm Maclure, Jane B. Sherwood, Geoffrey H. Tofler, James E. Muller, Murray A. Mittleman
Journal: Circulation (2012)

Acute psychological stress is associated with an abrupt increase in the risk of cardiovascular events. Intense grief in the days after the death of a significant person may trigger the onset of acute myocardial infarction (MI), but this relationship has not been systematically studied.We conducted a case-crossover analysis of 1985 participants from the multicenter Determinants of Myocardial Infarction Onset Study interviewed during index hospitalization for an acute MI between 1989 and 1994. We compared the observed number of deaths in the days preceding MI symptom onset with its expected frequency based on each patient's control information, defined as the occurrence of deaths in the period from 1 to 6 months before infarction. Among the 1985 subjects, 270 (13.6%) experienced the loss of a significant person in the prior 6 months, including 19 within 1 day of their MI. The incidence rate of acute MI onset was elevated 21.1-fold (95% confidence interval, 13.1-34.1) within 24 hours of the death of a significant person and declined steadily on each subsequent day. The absolute risk of MI within 1 week of the death of a significant person is 1 excess MI per 1394 exposed individuals at low (5%) 10-year MI risk and 1 per 320 among individuals at high (20%) 10-year risk.Grief over the death of a significant person was associated with an acutely increased risk of MI in the subsequent days. The impact may be greatest among individuals at high cardiovascular risk.
Baseline screening and psychosocial results from the UK SIGNIFY study: A whole-body MRI screening study in <i>TP53</i> mutation carriers and matched controls.
Authors: Ros A. Eeles, Elizabeth Bancroft, Sibel Saya, Emma Killick, Richard W Whitehouse, Dow-Mu Koh, Syed A Sohaib, Leslie Walker
Journal: Journal of Clinical Oncology (2017)

1520 Background: In the United Kingdom, current screening guidelines for TP53 germline mutation carriers solely recommends annual breast MRI, despite the wide spectrum of malignancies typically seen in this group. Some centres employ family specific screening with most centres having an “open-door” policy. Recent evidence suggests there may be a survival benefit with more intensive screening, including whole-body MRI. There are no published data on the psychological impact of such screening programmes. Methods: This study sought to investigate the role of one-off non-contrast whole-body MRI (WB MRI) in the screening of asymptomatic TP53 mutation carriers aged over 18 years. Clinical and psychological endpoints were assessed. Scans were read by radiologists blinded to participant carrier status. The incidence of malignancies diagnosed in TP53 mutation carriers against general population controls was calculated. The incidences of non-malignant relevant disease and irrelevant disease were measured, as well as the number of investigations required to determine relevance of findings. A series of questionnaires is used to assess the psychological impact of screening. Results: 44 TP53 mutation carriers and 44 population controls were recruited. In TP53 mutation carriers, six of 44 (13.6%, 95% CI: 5.2%-27.4%) participants were diagnosed with cancer during the study, all of which would be considered life threatening if untreated. Two were found to have two primary cancers. Two participants with cancer had abnormalities on the MRI which were initially thought to be benign (a pericardial cyst and a uterine fibroid) but transpired to be sarcomas. No controls were diagnosed with cancer. Fifteen carriers (34.1%, 95% CI: 20.5%-49.9%) and 7 controls (15.9%, 95% CI: 6.6%-30.1%) underwent further investigations following the WB MRI for abnormalities that transpired to be benign (p = 0.049). To date, there is no evidence of clinically significant adverse psychosocial effects. Conclusions: The cancer detection rate in this group justifies a minimum baseline non-contrast WB MRI in germline TP53 mutation carriers. Clinical trial information: NCT01737255.
FDA analysis of grade 3-4 safety events.
Authors: Marie-Anne Damiette Smit, Sandra J. Casak, Steven Lemery, Patricia Keegan, Amy E. McKee
Journal: Journal of Clinical Oncology (2017)

2544 Background: In new drug/biologics applications, safety data provided to FDA include serious adverse events (SAEs), defined as adverse events (AEs) resulting in death, life-threatening AE, inpatient hospitalization or prolongation of hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or congenital anomaly/birth defect. One limitation of the SAE definition is that hospitalization practices differ across localities and among medical practitioners. Therefore, a safety signal may not be adequately reflected when analyzing SAEs. We hypothesize that evaluating CTCAE Grade 3 (severe) and Grade 4 (life-threatening) AEs, independent of whether or not these were classified as serious, provides a more complete assessment of patient safety. Methods: We reviewed SAEs from all nine registrational trials for new molecular entities approved for the treatment of cancer by the FDA in 2014. Results: A total of 25,548 AEs were reported in 1,781 patients treated with an investigational agent. There were 2,943 Grade 3-4 AEs and 912 Grade 3-4 SAEs. Information regarding hospitalization was available in 62% of Grade 3-4 AEs. Fifty-five percent of Grade 3-4 SAEs vs. 5.5% of Grade 3-4 non-serious AEs resulted in hospitalization. Several clinically serious Grade 3-4 AEs, including sepsis and respiratory failure, were not classified as SAE. Conclusions: There is significant overlap in most common Grade 3-4 AEs and most common Grade 3-4 SAEs. Most AEs that are clinically serious were appropriately classified as SAE. However, some clinically serious AEs and some AEs resulting in hospitalization were not classified as SAE. With the exception of information regarding hospitalization, characterization of the reason why certain AEs were classified as SAEs was not possible. In this pooled analysis, data from the analysis of AEs by severity was more informative than the analyses by SAEs. [Table: see text]
Ballon intragastrique Bioenterics avant chirurgie bariatrique laparoscopique pour traitement de l'obésité massive: étude pilote
Authors: P Bulois, H Alfalah, F Ghazal, V Maunoury, T Jany, L Arnalsteen, M Romon, F Pattou
Journal: Endoscopy (2006)

La chirurgie bariatrique par laparoscopie peut être techniquement difficile voire impossible en cas d'obésité massive. Dans cette situation, une perte de poids pré-opératoire pourrait réduire la morbidité du traitement. Le but de ce travail était d'évaluer l'intérêt de la mise en place perendoscopique d'un ballon intragastrique en préparation à la chirurgie dans le cadre du traitement de l'obésité chez des patients dont l'indice de masse corporelle (IMC) était supérieur à 55kg/m2.
Diagnostic Accuracy of Fecal Immunochemical Test in Patients at Increased Risk for Colorectal Cancer
Authors: Anastasia Katsoula, Paschalis Paschos, Anna-Bettina Haidich, Apostolos Tsapas, Olga Giouleme
Journal: JAMA Internal Medicine (2017)

<h3>Importance</h3> The potential role of the fecal immunochemical test (FIT) for screening patients at increased risk for colorectal cancer (CRC) has not yet been elucidated. <h3>Objective</h3> To assess the diagnostic accuracy of FIT for CRC or advanced neoplasia (AN) in asymptomatic patients at above-average risk. <h3>Data Sources</h3> MEDLINE, EMBASE, Cochrane Library, and gray literature sources through August 2016. <h3>Study Selection</h3> Diagnostic studies evaluating the accuracy of FIT for CRC or AN in patients with a personal or familial history of CRC using colonoscopy as the reference standard. <h3>Data Extraction and Synthesis</h3> Two authors (A.K. and P.P.) independently extracted data and evaluated study quality using the Quality Assessment of Diagnostic Accuracy Studies–2 tool, and evaluated the quality of the body of evidence by means of GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Hierarchical models were used to synthesize available evidence. <h3>Main Outcomes and Measures</h3> The primary outcome was the diagnostic performance of FIT for detecting CRC or AN. <h3>Results</h3> We included 12 studies (6204 participants). Seven studies were deemed at high or unclear risk of bias. The average sensitivity of FIT for CRC was 93% (95% CI, 53%-99%), and the average specificity was 91% (95% CI, 89%-92%), yielding a positive likelihood ratio (LR+) of 10.30 (CI 7.7-13.9) and a negative likelihood ratio (LR−) of 0.08 (95% CI, 0.01-0.75) (GRADE: very low). The average sensitivity of FIT for AN was 48% (95% CI, 39%-57%); and the average specificity was 93% (95% CI, 91%-94%), yielding an LR+ of 6.55 (95% CI, 5.0-8.5) and an LR− of 0.57 (95% CI, 0.48-0.67) (GRADE: very low). Subgroup analyses indicated that FIT cutoff values between 15- and 25-μg/g feces provided the best combination of sensitivity and specificity for the diagnosis of CRC (93% and 94%, respectively). Quantitative and 1-sample FIT showed adequate test performance, but data on other FIT brands and multiple samples were insufficient. <h3>Conclusions and Relevance</h3> The FIT has high overall diagnostic accuracy for CRC but moderate accuracy for AN in patients at above-average personal or familial risk. Heterogeneity and wide confidence intervals limit the trustworthiness of our findings.
Prevalence of androgen receptors expression in triple negative breast cancer patients and its correlation with clinicopathological criteria: Our institutes experience.
Authors: Kamel Farag, Ola Elfarargy, Shereen El Shorbagy, Safa Ahmed, Ola Harb, Reham Amin, Loay Gertallah, Ola Megahed, Rasha Abdel-latif
Journal: Journal of Clinical Oncology (2017)

e12584 Background: Triple negative breast cancer (TNBC) is a term that has been applied to breast cancers which lack expression of three receptors: estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2). It represents about 20% of breast cancers diagnosed worldwide. TNBC is a challenging type by its presentation criteria and limited options of treatment. Continuous research for finding specific target is the aim of scientists. Androgen receptors (AR) expression take special attention in this type of breast cancer as its expression can help for finding special targeted treatment as antiandrogen therapy.Purpose:is to assess the AR expression in TNBC patients and to correlate its expression with clinicopathological parameters and disease outcome of patients in study populations. Methods: This prospective study included 90 female patients confirmed as TNBC patients in medical oncology and clinical oncology departments, in Mansoura University and Zagazig University, Egypt, between December, 2013 to May, 2016. AR positive expression was defined as ≥10% nuclear immunostaining. Results: AR expression was positive in twenty seven (27/90) patients (30% ), and lack of its expression was significantly associated with younger age group(p &lt; 0.001), higher grade(p = 0.017)&amp; higher tumor stage(p &lt; 0.001), presence of lymph node metastasis(p &lt; 0.001) &amp; distant metastases(p = 0.032), vascular(p = 0.044)&amp; perineural invasion and high baseline CA 15-3 level (p &lt; 0.001).Median follow up duration was 17.5months (range 6-40), 32/90 died (35.6%).Mean OS was 28months for AR negative TNBC patients versus 32months for AR positive patients. Twenty four of died patients (24/32) were AR negative. Three years OS was 50.8% and 44.1% for AR positive and AR negative respectively, but with nonsignificant P-value. Conclusions: Our study confirmed that AR positive expression in TNBC is a good prognostic feature and it can be sued as target for antiandrogen therapy in this group who is lacking any targettreatment.
Effectiveness and equity of sugar-sweetened beverage taxation
Authors: Sanjay Basu, Kristine Madsen
Journal: PLoS Medicine (2017)

Given the global epidemics of obesity, type 2 diabetes, and associated cardiovascular disease, numerous strategies are being discussed and implemented to reduce the risk of excess calorie intake and the adverse metabolic effects of unhealthy sugar consumption.While individuallevel interventions such as educational and behavioral modification strategies have been extensively researched, they remain difficult to effectively implement in large populations.Hence, fiscal and regulatory interventions such as sugar-sweetened beverage (SSB) taxation have been widely discussed.SSB taxation is of particular interest given consistent evidence associating SSB consumption with elevated risk of metabolic and cardiovascular disease and the lack of any known positive value of SSBs for nutrition or human health.Moreover, SSBs can be isolated from other foods easily, there are negative externalities of SSB consumption in terms of excess healthcare and disability costs, and strong evidence exists to indicate that taxation has been an effective means for reducing consumption of other unhealthy products such as tobacco [1][2][3][4].Contributing to the debate on the public health case for taxing SSBs, 2 recent articles in PLOS Medicine [5,6] add to the evidence concerning SSB taxation, which has mostly come from Mexico after the country implemented an approximately 10% tax on SSBs in 2014 [7][8][9][10].The new articles address major questions about the effects of SSB taxation: Are SSB taxes passed through from retailers to consumers, and, if so, are the price increases sufficient to reduce SSB consumption?Does substitution of SSBs by other beverages or foods neutralize the benefits of the tax; and does the tax harm retailers or consumers, particularly consumers of low socioeconomic status (SES)? SSB data from Berkeley, CaliforniaIn the first of the 2 articles, Barry Popkin and colleagues performed a study of prices, sales, consumer spending, and beverage consumption before and after a penny-per-ounce tax on SSBs that was implemented starting in March 2015 in Berkeley, California, United States [5].The authors made an extensive effort to triangulate data from stores, sales databases, and telephone surveys of adults in Berkeley.Importantly, sales data analyses included adjacent comparison cities that did not institute a tax, helping to isolate the effects of the tax from macroeconomic conditions that can affect beverage purchases over time, preexisting trends, regional media campaigns that both favored and opposed the tax, and other social and cultural influences on SSB sales across the region.Popkin and colleagues' results, consistent with a previous report [11], reveal that the SSB tax in Berkeley was generally passed through to consumers; notably, pass-through was substantial at the major chain supermarkets at which most SSBs are purchased but not at small
Changes in survival of primary central nervous system lymphoma based on a review of national databases over 40 years.
Authors: Joe Sammy Mendez, Ostrom T Quinn, Carol Kruchko, Jill Barnholtz-Sloan, Christian Grommes
Journal: Journal of Clinical Oncology (2017)

2040 Background: There has been significant improvement in treatment outcomes of Primary Central Nervous System Lymphoma (PCNSL) at specialized centers over past decades, and it is unclear if these changes have translated to benefits in the general population. In this study, we utilized national databases to examine survival trends over time. Methods: Incidence rates were obtained from the Central Brain Tumor Registry of the United States (CBTRUS, 2000 – 2013) and 18 Surveillance, Epidemiology and End Results (SEER, 1973 – 2013) registries. Data for survival analysis was obtained from SEER and analyzed using SEER*STAT. To focus on non-HIV-associated PCNSL, patients with “other infectious and parasitic diseases including HIV” as cause of death and follow up were excluded. CBTRUS identified 19,027 patients over 13 years and SEER 6,765 over 40 years. Results: The annual incidence of PCNSL in 2013 was 0.4 per 100,000 population (CBTRUS/SEER). Incidence increased from 0.1 per 100,000 in the 1970s to 0.4 per 100,000 in the 1980s, correlating with an increase in the diagnosis of elderly patients, ≥70 (1973:0.2 vs 2013:2.1 – SEER). Incidence rates differed greatly between young and elderly patients (20-29: 0.08 vs 70-79: 4.32 – CBTRUS). The median overall survival (mOS) of all patients is 17 months (m) with no survival benefit based on sex. Survival doubled from 12.5 m in the 1970s to 26 m in the 2010s. There was a significant difference in survival based on age: &lt; 50: 83 m vs 50-69: 25 m vs ≥70: 6 m (p-value &lt; 0.0001). In patients &lt; 50, mOS increased from 35.5 m in the 1970s to 134 m in the 2000s (mOS not achieved in 2010s). In patients 50-69, mOS increased from 8 m in the 1970s to 35 m in the 2010s. However, mOS in the elderly population, ≥70, has not changed in the last 40 years (6 m in the 1970s vs 7 m in the 2010s, p-value = 0.1). Conclusions: PCNSL is a disease that more frequently affects the elderly. Although overall survival has increased over the past 4 decades, reflecting current literature in PCNSL, survival in the elderly has not changed since the 1970s. Identification of this vulnerable patient population highlights the need for clinical trials targeting the elderly in hopes of improving treatment strategies and ultimately outcomes.
Recommandations professionnelles: perceptions et facteurs influençant leur application
Authors: P Vignally, F Grimaud, R Sambuc, M Barthet, JC Grimaud
Journal: Endoscopy (2006)

A l'heure où l'évaluation médicale franchit un nouveau cap avec l'instauration de la démarche d'Evaluation des Pratiques Professionnelles (EPP) par la Haute Autorité de Santé (HAS) à l'ensemble du corps médical, nous nous sommes intéressés aux perceptions des gastro-entérologues (GE) vis à vis des recommandations professionnelles (RP) et à la place que celles-ci ont dans leurs pratiques. Cette démarche, en effet, attribue aux recommandations professionnelles un statut de référence incontournable à l'évaluation des pratiques médicales.
Knee pain in a 15 year old boy
Authors: Robert Miller, Oliver Beaumont, Jakob van Oldenrijk
Journal: BMJ (2017)

A 15 year old boy presented after injuring his left knee while carrying a tray of food at a fast food restaurant. He felt his left knee “wobble” and immediately fell to the floor, unable to bear weight due to pain. On presentation to the emergency department, examination showed a laterally dislocated patella, which was reduced.

After reduction, examination showed a moderate effusion with some pain on palpation focused around the medial patellofemoral ligament. Range of movement was reduced to an extension-flexion of 0/10/60 degrees. Tests for ligamentous injury were unremarkable and the patient was able to resume weight bearing with the aid of crutches.

He had a Beighton score of 6, where 9 is a maximum score indicating joint laxity, despite having no history of joint dislocations. His medical history included chronic fatigue syndrome.

On follow-up two weeks later, the patient complained of intermittent locking in the left knee since the injury. On examination there was a joint effusion and a palpable loose body under the patella.



Fig 1  Anteroposterior (1) and lateral (2) radiographs after patella reduction at initial presentation



### 1. Do the original radiographs (fig 1⇑) show any abnormalities, and what further imaging should be considered for this patient?

#### Short answer

The original radiographs show a lipohaemarthrosis and an osteochondral fragment (fig 2⇓). Further imaging could include additional plain radiographs, a computed tomography (CT) scan to delineate bony injuries, and a magnetic resonance imaging (MRI) scan for soft tissue injuries.



Fig 2  Annotated anteroposterior (1) and lateral …
Incentive Spirometry After Bariatric Surgery
Authors: Ana Fernandez-Bustamante, Jonathan Schoen, Marcos F. Vidal Melo
Journal: JAMA Surgery (2017)

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