tbuckley/cabot-search huggingface dataset:
Triple-NOTE (Triple Negative Outcome in ESME): Large recent real-world prognostic data on triple negative metastatic breast cancers (mTNBC).
Authors: Marie-Paule Sablin, Corinne Tchokothe, Delphine Loirat, Thomas Denis Bachelot, Emmanuelle Fourme, Matthieu Carton, Meriem Mokdad-Adi, Delphine Berchery, Christelle Levy, William Jacot, Frederique Madeleine Penault-Llorca, Anthony Goncalves, Laurence Vanlemmens, Jean-Christophe Eymard, Mario Campone, Gaetane Simon, Mathieu Robain, Christian Cailliot, Christophe Le Tourneau, Francesco Ricci
Journal: Journal of Clinical Oncology (2017)

e12592 Background: During last decade, therapeutic arsenal has expanded for metastatic breast cancer (mBC), but few data are available about mTNBC, a poor prognosis subtype. In 2014, UNICANCER (composed of 18 French Comprehensive Cancer Centers) launched the Epidemiological Strategy and Medical Economics (ESME) program to centralize real-world data. This base represents a great opportunity to update the outcomes and the treatment practice patterns of this population. Methods: The ESME-mBC database was built from information systems, treatment databases and patients’ electronic files including quality control processes. All pts who initiated treatment for mBC between 01-Jan-2008 and 31-Dec-2014 were selected. The primary objective of this study was to assess overall survival (OS) of mTNBC pts. TNBC status was defined as ER and PR &lt; 10% in both primary and metastatic disease, as well as the absence of overexpression or amplification of HER2. The secondary objectives were to describe the characteristics of this population, clinical management (duration and sequence of treatments) and to evaluate the prognostic value of several clinical factors (age, distant disease free interval, location and number of metastatic sites) Results: Among 16703 pts in the ESME-mBC database, 2368 (14%) had mTNBC. Median OS over this time period was 14.8 months (95% CI 14-15.6). Median age at diagnosis of mBC was 57 years. For the pts who relapsed, median metastasis free interval was 24 months, while 25.5% of the pts were de novo metastatic. 61% of the pts presented visceral metastasis and 12% had cerebral metastasis as first metastatic site. The pattern of metastatic involvement (visceral and cerebral) and a short metastasis free interval ( &lt; 24 months) were the most important prognostic factors in multivariate analysis. The description of treatment sequences (duration, prognostic value) will be presented. Conclusions: In this real-life setting database, mTNBC remain of poor prognosis despite a trend for a better OS than the historical data available (12-13 ms). This TNBC ESME cohort is one of the largest available and offers an updated assessment of the outcomes of this population.
Become one with the force: optimising mechanotherapy through an understanding of mechanobiology
Authors: Stuart J Warden, William R Thompson
Journal: British Journal of Sports Medicine (2017)

The musculoskeletal system generates, absorbs and transmits force, enabling functional movement.Given this mechanical role, it follows that musculoskeletal tissues adapt to mechanical demands.Mechanical forces direct musculoskeletal cellular activities, altering tissue mass, structure and/or quality (figure 1). 1 The net result is altered tissue-level stresses and strains to applied loads and, subsequently, altered injury risk.
A simple, validated model for identifying cases that are unlikely to benefit from the 21-gene recurrence score (RS) assay.
Authors: Michele Maiko Gage, Martin Rosman, Charles Mylander, Erica Giblin, Hyun-seok Kim, Leslie Cope, Chris Umbricht, Antonio C. Wolff, Lorraine Tafra
Journal: Journal of Clinical Oncology (2014)

540 Background: Predicting recurrence risk and chemotherapy benefit in breast cancer can be challenging, and OncotypeDx (ODX) is often used to gain insight. Using readily available clinical information, a simple model was created to identify high and low risk patients, saving the expense of ODX testing. Methods: Clinical-pathologic data from 221 hormone positive, HER2-negative invasive breast cancer patients was used to create a model with two simple rules: Low Grade and Positive PR tumors (LG+PR) are low risk, and High Grade or Low ER (ER<20%) tumors (HG/LER) are high risk. The TAILORx trial thresholds of RS≤10, where chemotherapy is of limited benefit, (TXNC) and RS≥26 supportive of chemotherapy (TXC) were used to judge model performance. The model was then validated on an independent second institution’s set of 319 patients. Results: Most HG/LER were RS≥26, (84% on development set, 51% on #2 set), and most LG+PR were RS≤18 (83%, 74%, respectively). Refer to Table for distribution. Impressively, the 2-Step Errors for HG/LER (RS ≤10) were 0% and 2%, and for LG+PR (RS≥26) were 0% and 2.6%, showing it is very unlikely for HG/LER to have a low risk test result or for LG+PR to have a high risk test result.In the validation set, 28% of the indeterminate group result as high or low risk; this group may clinically benefit from ODX. Conclusions: In HG/LER and LG+PR, ODX is not clinically valuable because it consistently results in a RS in which benefit of chemotherapy is accepted or unknown for HG/LER, and benefit of chemotherapy is rejected or unknown for LG+PR. The equal hazard ratios of RS and high grade, as evaluated by a multivariate Cox model (using age, pathologic variables, and RS) (Paik et al. NEJM ‘04), further support the importance of grade when predicting risk. By identifying patients who are unlikely to benefit from ODX testing, expense will be spared. ODX low risk ODX intermediate ODX high risk TXNC TXI TXC Data Set RS ≤10 11-17 18-25 26-30 31+ Total Institution #1 Development Group HG/LER 0 2 4 6 25 37 Indeterminate 19 41 35 8 8 111 LG+PR 27 33 13 0 0 73 Total 46 76 52 14 33 221 Institution #2 HG/LER 1 10 13 7 18 49 Indeterminate 39 88 78 16 11 232 LG+PR 11 17 9 0 1 38 Total 51 115 100 23 30 319 Abbreviation: TXI, TAILORx Indeterminate.
Nipple skin-sparing mastectomy: 15 year experience of expanding indications.
Authors: Amy Elizabeth Rivere, Kara M Spinks, James Yuen, Keith Wolter, Daniela A Ochoa, Ronda S. Henry-Tillman, Lauren E Eads, Soheila Korourian, V. Suzanne Klimberg
Journal: Journal of Clinical Oncology (2016)

1060 Background: Skin-sparing mastectomy and reconstruction (SSM) is widely performed for Stage I, II and III breast cancer, but surgeon reluctance to perform nipple skin-sparing mastectomy and reconstruction (NSSM) persists for some indications. The aim of our study is to compare complications and recurrence rates of patients undergoing SSM and NSSM for various indications including locally advanced disease and genetic susceptibility to breast cancer, demonstrating safety compared to SSM. Methods: This retrospective study of a prospective database analyzed data of patients who underwent either SSM or NSSM from 2001-2015 at a single institution to assess the oncologic outcomes and complication rates of SSM compared to NSSM. Results: Six-hundred six patients underwent 1,060 NSSM or SSM (388 SSM, 672 NSSM) for Stage 0-III breast cancer and genetic predisposition with an average follow-up of 51 ± 33 months, and 146 patients had ≥ 5-year follow-up. Overall complication rates were equal at 18%(39/216) for SSM and 18%(63/349) for NSSM, p = ns. Ischemic related complications involving wound breakdown, necrosis, and dehiscence requiring intervention occurred in 8.3%(18/216) SSM and 8.3%(29/349) NSSM, p = ns, which includes 2.2%(8/349) of NSSM with nipple necrosis, 1.4%(5/349) complete, 0.85%(3/349) partial nipple loss. Infectious complications occurred in 4.1%(9/216) SSM and 4.6%(16/349) NSSM, p = ns. There was a local-regional recurrence rate of 1.4%(3/216) SSM and 2.5%(9/349) NSSM, p = 0.34 and development of metastatic disease progression in 1.8%(4/216) SSM and 2.8%(10/349) NSSM, p = 0.45. Conclusions: NSSM is safe compared to SSM for Stage 0-III breast cancer, including those with locally advanced disease and those with genetic predisposition to breast cancer.
Journées Francophones de Pathologie Digestive 2006 – Le point sur les résumés concernant l'endoscopie digestive
Authors: B Napoléon
Journal: Endoscopy (2006)

Comme chaque année, à l'occasion des Journées Francophones de Pathologies Digestives qui regroupent plus de 4000 congressistes à Paris, une place importante est réservée aux nouveautés en endoscopie digestive. Vous retrouverez ci-dessous un rapide aperçu des présentations les plus marquantes, ainsi que l'ensemble des abstracts concernant l'endoscopie.
Metaplastic progression free survival compared to triple negative breast cancer, a retrospective analysis.
Authors: Maryam B. Lustberg, Amanda Luff, Gregory S. Young, Rachel M. Layman, Ewa Mrozek, Raquel E. Reinbolt, Robert Wesolowski, Bhuvaneswari Ramaswamy
Journal: Journal of Clinical Oncology (2016)

e12552 Background: Metaplastic breast cancer (MBC) is a histologically diverse sub-type of invasive breast cancer accounting for less than 1% of all breast cancers. MBC are often triple negative (TNBC) but historically have worse prognosis. With advancement in adjuvant therapy in the last decade, we aimed to determine differences in outcomes between MBC and TNBC in a retrospective case matched analysis. Methods: A retrospective chart review of breast cancer patients at The Ohio State University James Cancer Hospital 2001-2014 was performed. Patients treated for TNBC or MBC were identified and a matching schema of 3 TNBC patients to each MBC was used, matching for stage of breast cancer (1-4) and age within 10 years to make the TNBC comparable to the MBC sample on these covariates. Chemotherapy within 6 months of diagnosis, radiotherapy, and surgical treatments were compared using Fisher’s exact test. PFS and OS were compared using log-rank tests. Survival was censored at last contact date indicated in medical records. Results: 403 TNBC and 48 MBC cases were identified, and 98 were eliminated for missing follow up or inconsistent staging.There were three matches for all MBC cases except a 93 year old with stage 1 disease with only one match. The final analysis set contained 82 TNBC and 28 MBC. Due to matching, median age in both groups was 49 years and distribution of stage was comparable. At median follow up of 2.8 years, 2 TNBC and 4 MBC progressed and 2 TNBC and 3 MBC died. MBC was associated with significantly worse PFS compared to TNBC (3year TNBC: 95% MBC: 76% p = 0.001). There was a trend toward worse OS in MBC but this was not statistically significant (3year TNBC: 93% MBC: 84% p = 0.2). There was no significant difference in treatment modalities or chemotherapy between groups (Anthracycline TNBC: 67.1% MBC: 67.9% p = 1.00; Paclitaxel TNBC: 48.8% MBC: 47.3% p = 0.66; Docetaxel TNBC: 7.3% MBC: 7.1% p = 1.00). Conclusions: MBC is significantly correlated with worse PFS compared to TNBC after matching for stage and age at diagnosis. In this study, both groups had similar multimodality treatment yet MBC had worse outcomes. Further studies are needed to improve outcomes in this rare and aggressive type of breast cancer.
An open-label, single-arm, phase II study of pertuzumab with high-dose trastuzumab for treatment of central nervous system (CNS) progression post-radiotherapy in patients (pts) with HER2-positive metastatic breast cancer (MBC): PATRICIA.
Authors: Nancy U. Lin, Catherine Lai, Andrea Lacasia, Alisha Stein, Bongin Yoo, Anita Fung, Mark D. Pegram
Journal: Journal of Clinical Oncology (2016)

TPS633 Background: CNS metastases are observed in up to half of pts with HER2-positive MBC, with incidence likely to rise due to improved systemic treatments and longer overall survival (OS). While radiotherapy can be effective, there are toxicity issues and pts frequently progress. CNS response to existing systemic therapies has been poor; there is no approved treatment for HER2-positive brain metastases in pts with MBC. Combination of the HER2-targeted monoclonal antibodies trastuzumab and pertuzumab provides more comprehensive blockade of HER2 than either agent alone. Trastuzumab concentrations in the CNS increase with an impaired blood–brain barrier (BBB), and preclinical models suggest subtherapeutic levels may be related to insufficient dosing rather than inability to cross the BBB. Higher doses of trastuzumab have not been associated with increased toxicity. PATRICIA is evaluating addition of pertuzumab and high-dose trastuzumab to current systemic treatment for HER2-positive MBC in pts with CNS progression post-radiotherapy and stable systemic disease. Methods: This study is enrolling pts with HER2-positive MBC and new and/or progressive CNS lesions > 60 days after whole-brain radiotherapy or stereotactic radiosurgery for CNS metastases, and stable systemic disease. Pts must have a baseline left ventricular ejection fraction ≥ 50% and no significant history of cardiac disease. Pts will receive intravenous (IV) pertuzumab (840 mg loading dose, then 420 mg q3w) plus high-dose IV trastuzumab (6 mg/kg qw) in addition to their current systemic therapy (except ado-trastuzumab emtansine, lapatinib, or anthracyclines). The primary endpoint is objective response rate in the CNS. Secondary endpoints include duration of CNS response, progression-free survival (CNS and/or non-CNS), OS, and safety. The study will be stopped at an interim analysis (15 pts ≥ 2 cycles) if there is no clinical benefit or if ≥ 2 pts have congestive heart failure events related to trastuzumab or pertuzumab. Target enrollment is 40 pts. This US-based trial opened in September 2015. Clinical trial information: NCT02536339.
The impact of intratumoral heterogeneity on the prognosis of ER-positive/HER2-negative breast cancer.
Authors: Masahiro Oikawa, Mayumi Ishida, Yoshiaki Nakamura, Sumiko Nishimura, Chinami Koga, Akihiro Saruwatari, Akiko Igawa, Sayuri Akiyoshi, Yumiko Koi, Shinji Ohno
Journal: Journal of Clinical Oncology (2014)

563 Background: In this study, we assessed the clinical importance of minor HER2-amplified clones in ER-positive, HER2-negative breast cancer to demonstrate the impact of intra-tumoral heterogeneity on clinical outcome. Methods: We retrospectively mined clinical data from the National Kyushu Cancer Center (2008–2013) for surgically resected, primary invasive breast cancers, that were ER-positive and HER2 IHC 2+/FISH-negative (HER2:CEP17 signal ratio by FISH < 2.0). Samples were classified as minor clone (MC) (+) or MC (−) if they had minor clones with HER2:CEP17 ratios ≥ 3.0 or not, respectively. The clinicopathological findings including age, menopausal status, tumor size, lymph node metastasis, lymphatic invasion, PgR, Ki67 labeling index and chemotherapy were analyzed between the two groups by Fisher’s exact test and the Wilcoxon rank-sum test. Survival curves were estimated using the Kaplan–Meier method and the significance of differences between survival curves was determined using the log-rank test. Results: Of the 149 cases, with mean follow-up period of 732 days, 87 cases (58.4 %) and 62 cases (41.6 %) were classified as MC (+) or MC (−), respectively. When comparing the clinicopathological findings between these two groups, the MC (+) group tended to have larger tumor size (mean size 20.6 mm vs. 18.9 mm, P = 0.078), had a significantly higher Ki67 labeling index (with mean of 36.2 % vs. 22.8%, P = 0.036), and a significantly higher ratio of receiving chemotherapy (59.8% vs. 41.9%, P = 0.045). The MC (+) group showed worse overall survival (OS) compared with the MC (−) group (P = 0.026), while the difference in disease-free survival (DFS) was not significant. Conclusions: Among ER-positive, HER2-negative invasive breast cancers, the subgroup with HER2-amplified minor clones showed more biologically aggressive features, which may have an impact on prognosis. Intra-tumoral heterogeneity should therefore be considered in breast cancer therapy, and further investigation is required.
Long-term volume-targeted pressure-controlled ventilation: sense or nonsense?
Authors: Maria Paola Arellano-Maric, Cesare Gregoretti, Marieke Duiverman, Wolfram Windisch
Journal: European Respiratory Journal (2017)

The technology underlying the development of novel ventilatory modes for long-term noninvasive ventilation of patients with chronic hypercapnia is continuously evolving. Volume-targeted pressure-controlled ventilation is a hybrid ventilation mode designed to combine the advantages of conventional ventilation modes, while avoiding their drawbacks. However, manufacturers have created different names and have patented algorithms and set-up variables, which can result in confusion for physicians and respiratory therapists. In addition, clear evidence for the superiority of this novel mode has not yet been established. These factors have most likely hindered more widespread use of this mode in clinical practice. The current review presents the rationale, working principles, characteristics and set-up recommendations associated with volume-targeted modes. In addition, it summarises the clinical and laboratory studies that have challenged this mode.
Association of Socioeconomic Status in Childhood With Left Ventricular Structure and Diastolic Function in Adulthood
Authors: Tomi T. Laitinen, Elina Puolakka, Saku Ruohonen, Costan G. Magnussen, Kylie J. Smith, Jorma S. A. Viikari, Olli J. Heinonen, Noora Kartiosuo, Nina Hutri-Kähönen, Mika Kähönen, Eero Jokinen, Tomi P. Laitinen, Päivi Tossavainen, Laura Pulkki-Råback, Marko Elovainio, Olli T. Raitakari, Katja Pahkala, Markus Juonala
Journal: JAMA Pediatrics (2017)

Increased left ventricular (LV) mass and diastolic dysfunction are associated with cardiovascular disease. Prospective data on effects of childhood socioeconomic status (SES) on measures of LV structure and function are lacking.To examine whether family SES in childhood was associated with LV mass and diastolic function after adjustment for conventional cardiovascular disease risk factors in childhood and adulthood.The analyses were performed in 2016 using data gathered in 1980 and 2011 within the longitudinal population-based Cardiovascular Risk in Young Finns Study. The sample comprised 1871 participants who reported family SES at ages 3 to 18 years and were evaluated for LV structure and function 31 years later.Socioeconomic status was characterized as annual income of the family and classified on a 3-point scale.Left ventricular mass indexed according to height at the allometric power of 2.7 and the E/e' ratio describing LV diastolic performance at ages 34 to 49 years.The participants were aged 3 to 18 years at baseline (mean [SD], 10.8 [5.0] years), and the length of follow-up was 31 years. Family SES was inversely associated with LV mass (mean [SD] LV mass index, 31.8 [6.7], 31.0 [6.6], and 30.1 [6.4] g/m2.7 in the low, medium, and high SES groups, respectively; differences [95% CI], 1.7 [0.6 to 2.8] for low vs high SES; 0.8 [-0.3 to 1.9] for low vs medium; and 0.9 [0.1 to 1.6] for medium vs high; overall P = .001) and E/e' ratio (mean [SD] E/e' ratio, 5.0 [1.0], 4.9 [1.0], and 4.7 [1.0] in the low, medium, and high SES groups, respectively; differences [95% CI], 0.3 [0.1 to 0.4] for low vs high SES; 0.1 [-0.1 to 0.3] for low vs medium; and 0.2 [0 to 0.3] for medium vs high; overall P < .001) in adulthood. After adjustment for age, sex, and conventional cardiovascular disease risk factors in childhood and adulthood, and participants' own SES in adulthood, the relationship with LV mass (differences [95% CI], 1.5 [0.2 to 2.8] for low vs high SES; 1.3 [0 to 2.6] for low vs medium; and 0.2 [-0.6 to 1.0] for medium vs high; P = .03) and E/e' ratio (differences [95% CI], 0.2 [0 to 0.5] for low vs high SES; 0.1 [-0.1 to 0.4] for low vs medium; and 0.1 [0 to 0.3] for medium vs high; P = .02) remained significant.Low family SES was associated with increased LV mass and impaired diastolic performance more than 3 decades later. These findings emphasize that approaches of cardiovascular disease prevention must be directed also to the family environment of the developing child.
A Potential Oligogenic Etiology of Hypertrophic Cardiomyopathy
Authors: Lili Li, Matthew Neil Bainbridge, Yanli Tan, James T. Willerson, Ali J. Marian
Journal: Circulation Research (2017)

Hypertrophic cardiomyopathy (HCM) is a prototypic single-gene disease caused mainly by mutations in genes encoding sarcomere proteins. Despite the remarkable advances, the causal genes in ≈40% of the HCM cases remain unknown, typically in small families and sporadic cases, wherein cosegregation could not be established.To test the hypothesis that the missing causal genes in HCM is, in part, because of an oligogenic cause, wherein the pathogenic variants do not cosegregate with the phenotype.A clinically affected trio with HCM underwent clinical evaluation, electrocardiography, echocardiography, magnetic resonance imaging, and whole exome sequencing. Pathogenic variants in the whole exome sequencing data were identified using established algorithms. Family members were genotyped by Sanger sequencing and cosegregation was analyzed. The siblings had a severe course, whereas the mother had a mild course. Variant analysis showed that the trio shared 145 heterozygous pathogenic variants in 139 genes, including 2 in cardiomyopathy genes TTN and ALPK3. The siblings also had the pathogenic variant p.Ala13Thr variant in MYL2, a known gene for HCM. The sibling's father also carried the p.Ala13Thr variant, in whom an unambiguous diagnosis of HCM could not be made because of concomitant severe aortic stenosis. The TTN variant segregated with HCM, except in a 7-year-old boy, who had a normal phenotype. The ALPK3 variant, shared by the affected trio, did not segregate with the phenotype.We posit that a subset of HCM might be oligogenic caused by multiple pathogenic variants that do not perfectly cosegregate with the phenotype.