tbuckley/cabot-search huggingface dataset:
PTHrP(12-48) for the diagnosis of breast cancer bone metastasis.
Authors: Charity L. Washam, Stephanie D. Byrum, Kim Leitzel, Ali M. Suhail, Allan Lipton, Larry J. Suva
Journal: Journal of Clinical Oncology (2012)

e21039 Background: Bone metastasis of breast cancer significantly compromises patient morbidity and mortality. Currently, no reliable methods detect or predict patients at increased risk for developing bone metastasis. We utilized 3 independent cohorts of breast cancer patients to validate a highly discriminatory plasma-based proteomic profile that identifies breast cancer bone metastasis. The identity of the most discriminatory protein component identified was a parathyroid hormone-related protein fragment, PTHrP(12-48). Methods: Plasma samples collected from 21 breast cancer patients with clinical evidence of a bone metastasis and 21 patients with no evidence of bone metastasis from time of diagnosis to clinical outcome were evaluated. A novel mass spectrometry-based assay using human serum spiked with synthetic PTHrP(12-48) was used to measure PTHrP(12-48) concentrations (pg/μl). Statistical significance was assessed by one-way ANOVA. ROC curves evaluated the diagnostic potential of PTHrP(12-48) and a simple logistic regression derived from the combined measurement of PTHrP(12-48) and NTx. Results: PTHrP(12-48) concentrations ranged between 11.6 and 92.1 pg/μl in bone metastasis patients and between 4.5 and 34.2 pg/μl in patients without bone metastases. PTHrP(12-48) was significantly increased in bone metastasis plasma (p &lt; 0.05). No significant correlation was identified between PTHrP(12-48) and NTx. ROC analysis of PTHrP(12-48), threshold 18 pg/μl, classified the two groups with high accuracy. Class prediction by the PTHrP(12-48)/NTx logistic regression model increased diagnostic specificity. Conclusions: The measurement of PTHrP(12-48) in patient plasma has potential as a viable clinical measure of bone metastasis. In combination with serum NTx, PTHrP(12-48) may assist in identifying bone metastases in patients presenting with low to normal bone turnover markers.
Next Generation Sequencing (NGS) Based IGH and TCR Clonality Assays Provide Excellent Specificity and Sensitivity for Routine Clonal Characterization and Monitoring of Lymphoproliferative Disorders
Authors: Maria E. Arcila, Mustafa Syed, Wayne Yu, Hannah Kim, JinYuan Yao, Caleb Ho, Kseniya Petrova-Drus, Mikhail Roshal, Jae H. Park, Ola Landgren, Ahmet Dogan, Khedoudja Nafa
Journal: Blood (2017)
Feasibility of group follow-up visit for breast cancer survivors
Authors: C. O. Ruud, K. Francis, C. Stephens, M. H. Rajab
Journal: Journal of Clinical Oncology (2007)

19603 Background: The ASCO 2006 guidelines specify that regularly scheduled follow-up care of breast cancer survivors should be the standard. Follow up care is a “teachable moment” to train survivors in positive habits. A group visit model at the Cleveland Clinic proved feasible and improved patient satisfaction for other diseases. Our objectives include assessing the feasibility of an adapted group follow-up visit for the care of breast cancer patients and patient satisfaction. Methods: A feasibility study targeting breast cancer patients who completed primary therapy and were scheduled for a routine appointment. We mailed letters inviting patients to a follow-up group visit. Patients were divided into 3 groups, each scheduled for a separate (90–120 minute). During the first half of the visit, participants were divided into three groups; 5-minute physician exam, nurse review of medications and vital signs, and instruction by a social worker. Groups were rotated. During the second half the doctor, nurse, and social worker met with all participants in one room starting with an educational presentation about fatigue and exercise. Each participant was subsequently interviewed by the physician in the presence of their peers. Shared complaints were investigated first. Patients rated their satisfaction with the different parts of the visit on a scale of 1–5. Participants were surveyed pre- and post- education session and asked if they would participate again. Participants were allowed to bring a family member or friend. Results: 29 (29.6 %) out of 98 consented and 22 (22.5%) attended;10 in first visit, 5 in second visit and 7 in last visit. Average age 61±8, ranged from 46–72 years. Most participants were satisfied with all parts of the group visit, except two in the first group were less satisfied with the check in process and moving between rooms. Comparing the pre- vs. post- educational session surveys showed an improved understanding of the importance of fatigue or exercise. 17 (77%) out of 22 participants agreed to participate in another group visit. Conclusion: Group visit format is feasible and provides patient satisfaction. No significant financial relationships to disclose.
GGCP041/09: A Galician study of second-line erlotinib in patients with advanced non-squamous non-small cell lung cancer (nsNSCLC).
Authors: Sergio Vazquez Estevez, Maria Jose Villanueva Silva, Jose Luis Firvida Perez, Martin Lazaro Quintela, Silvia Varela Ferreiro, Gerardo Huidobro Vence, Ovidio Fernandez Calvo, Begona Campos Balea, Joaquin Casal Rubio, Carmen Areses Manrique
Journal: Journal of Clinical Oncology (2012)

e18146 Background: Efficacy of oral erlotinib has been conclusively established in 2 nd line setting (BR.21 and TRUST studies) and the outcomes are similar to those provided by other approved chemotherapeutical agents (TITAN study). Higher responses rates have been found in p with Asian ethnicity, adenocarcinoma, women and never smokers, where predictive EGFR mutations occur more frequently; even though erlotinib has a significant effect on survival in all subgroups of patients. This observational study evaluates the efficacy of 2 nd line erlotinib in unselected p with nsNSCLC in 4 Galician institutions. Methods: Unselected p with advanced nsNSCLC were treated with 150 mg/day of erlotinib as 2 nd line therapy until unacceptable toxicity or progressive disease. EGFR mutational status was retrospectively tested when feasible, and serum carcinoembryonic antigen (CEA) monitored during the treatment period. Results: Baseline characteristics of 45 p included at the time of this analysis: mean age of 61.7 yrs. (range: 38-83); 80% male; 73.3% adenocarcinoma; 71.1% stage IV; 7/69/24% PS ECOG 0/1/2; 29/33/38 % never/current/former smokers. EGFR activating mutation testing was performed in 24 p (53%) and 2 positive cases were found (8%), both with metastatic adenocarcinoma (stage IV). The median PFS was 3.3 (95% CI: 1.6-5.1) and the median OS 10 months (95% CI: 7.5-12.5). Among p without EGFR mutations, erlotinib conferred a median OS of 8.1 months (95% CI: 1.4-14.9). Out of 31 p evaluable, radiologic response was achieved in 7 p (22.6%), for an overall disease control rate of 45.2 %. No unexpected toxicities were reported: 60 % of p experienced cutaneous toxicity (6.6 % grade ¾), 22.2% asthenia (4.4% grade ¾) and 17.8% diarrhea (2.2% grade ¾). Only 3 p discontinued due to adverse events. Conclusions: This study confirms the efficacy and safety of 2 nd line erlotinib in a clinical practice scenario and the outcomes in p with non-squamous NSCLC are equivalent to those reported with the chemotherapy for salvage therapy. Moreover, the absence of mutations does not preclude the benefit from the drug. Updated data of the study will be presented.
Non-Hodgkin lymphoma in children: Is 1 g/m<sup>2</sup> methotrexate as effective as 5 g/m<sup>2</sup> in advanced-stage nonlymphoblastic non-Hodgkin lymphoma?
Authors: Rejin Kebudi, Bulent Zulfikar, F Betul Cakır, Omer Gorgun, Inci Ayan, Oner Dogan
Journal: Journal of Clinical Oncology (2013)

10043 Background: Survival rates in non-Hodgkin lymphoma (NHL) have increased significantly in the last decades. This study aims to assess the demographic data and treatment results of children with nonlymphoblastic NHL treated in a single institution. Methods: 106 children (74 male, 32 female), treated in Istanbul University, Oncology Institute, between 9/1989-12/2012 were evaluated retrospectively. Nonlymphoblastic NHL received COMP until 1991. After then, all received BFM protocols. They received BFM 90 protocol with 5 g/m2 methotrexate (MTX) until 1995 and modified BFM protocol with 1 g/m2 MTX thereafter. Results:The median age was 8(2-19) years. Histopathologic subtypes: 81 Burkitt, 25 large cell. The primary location was abdomen in 51, mediastinum 4, head/neck 31, 20 other (bone 8, breast 2, ovaries 2, skin 2, paravertebral 2, other 4). Bone marrow was involved in 10, CNS in 2. 40 patients had stage I+II, 44 stage III, and 22 stage IV disease. 23 patients died, 7 due to toxicity, 2 with second malignancies (AML,GBM). 10 year survival and EFS in the whole group was 76 and 76 % respectively. 10 year survival was 100, 94.3, 71.3 and 50% in stage I, II, III, and IV. In advanced stage nonlymphoblastic NHL patients, 10 year survival was significantly higher in patients receiving BFM regimen with 1 g/m2 MTX, than in ones receiving COMP or BFM protocol with 5 g/m2 MTX (10 year S, 81%, 46.7%, 44.4% respectively). These results were also compared with 47 advanced stage nonlymphoblastic NHL patients treated with 5 g/m2 BFM protocol in another center in the same university in the same time period (5 year S 78 %). Conclusions: Survival rates in the whole group are in parallel with advances attained in the world in NHL. The significantly higher survival rates achieved in patients with advanced stage non-lymphoblastic patients receiving modified BFM (1g/m2MTX) may be due to the decreased toxicity seen in this group and to the advances in supportive care in the last decade. In another major center in the same university that used the same protocol with 5 g/m2 MTX in the same time period, similar survival rates suggest that 1 g/m2 MTX which is cheaper and less toxic is also as effective as 5 gr/m2 in these patients.
Response to: ‘Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients’ by Buch <i>et al</i>
Authors: Frances Humby, Myles Lewis, Michael J Townsend, Costantino Pitzalis
Journal: Annals of the Rheumatic Diseases (2019)

We would like to thank Professor Buch and colleagues for their interest and thoughtful comments regarding our manuscript,1 and we are grateful for the opportunity to provide further clarification on the clinical phenotype displayed by the rheumatoid arthritis (RA) patients with a pauci-immune pathotype analysed in our early arthritis cohort.2 We have segregated this group into anti-citrullinated peptide antibodies (ACPA) +ve and -ve subsets and analysed age distribution, disease activity score (DAS28) components, ultrasound (US) scores, joint biopsied and modified Sharp van der Heijde score (SHSS) components, as indicated by Buch and colleagues to evaluate whether significant differences in clinical parameters could be identified (table 1). …
MicroRNA-142 Is Critical for the Homeostasis and Function of Type 1 Innate Lymphoid Cells
Authors: Melissa M. Berrien-Elliott, Yaping Sun, Carly Neal, Aaron Ireland, Maria C. Trissal, Ryan P. Sullivan, Julia A. Wagner, Jeffrey W. Leong, Pamela Wong, Annelise Y. Mah-Som, Terrence N. Wong, Timothy Schappe, Catherine R. Keppel, Victor S. Cortez, Efstathios G. Stamatiades, Ming O. Li, Marco Colonna, Daniel C. Link, Anthony R. French, Megan A. Cooper, Wei-Le Wang, Mark P. Boldin, Pavan Reddy, Todd A. Fehniger
Journal: Immunity (2019)
Acute Ischemic Events in Patient Receiving Direct Oral Anticoagulants for Atrial Fibrilation: Incidence, Outcome and Clinical Profile
Authors: Pável Olivera, Olga Gavin, Eugènia Rivero, Mireia Constans, Crisitina Marzo, Granada Perea, Verónica Pons, Tania Canals, Erik Johansson, Francesc Bosch, Amparo Santamaría
Journal: Blood (2016)
The Fate of Patients with Refractory Diffuse Large B Cell Lymphoma (DLBCL)
Authors: Pavel Otahal, Andrea Janikova, David Belada, Vit Prochazka, Heidi Mocikova, Jan Pirnos, Juraj Ďuraš, Kateřina Kopečková, Vit Campr, Robert Pytlik, Petra Blahovcova, Marek Trneny
Journal: Blood (2018)
Breast cancer survivorship visits: Presenting concerns and resulting recommendations.
Authors: Carrie Tompkins Stricker, Linda A. Jacobs, SarahLena Panzer, Steven C Palmer
Journal: Journal of Clinical Oncology (2013)

e20553 Background: Survivorship care plans (SCPs) are mandated for cancer patients following initial cancer therapy. However, appropriate content, processes, and outcomes of survivorship visits are not yet defined. Neither the concerns that patients bring to these visits nor the degree to which they recall information given by providers is known. As part of a multicenter pilot study of breast cancer survivorship visits, we examined patient concerns at time of presentation for such visits, as well as patient and provider perceptions of resulting recommendations. Methods: We assessed post-treatment breast cancer survivors’ (BCSs’) survivorship concerns prior to a survivorship visit at 1 of 9 cancer centers associated with the LIVESTRONG Survivorship Center of Excellence Network. Following that visit we queried providers as to what referrals and recommendations were made during the visit. Three months later we asked patients to report what recommendations were made by providers. We then examined prevalence of patient concerns and agreement between patients and providers concerning survivorship visit recommendations for managing health. Results: 103 BCS at 9 centers participated. BCS most endorsed concerns were reducing risk of recurrence (81.4%), receipt of appropriate breast cancer follow up care (57.4%), weight loss (55.5%), risk for second cancers (54.9%), fatigue/sleep management (50.0%), and symptoms important to report to providers (50.0%). Although exercise was recommended to 63% of participants by providers, patients recalled this correctly only 79% of the time (Kappa = .16, ns). Moreover, there was a generally poor concordance between provider-reported and patient-recalled recommendations, with kappas ranging from 0.46 for recommendations about tobacco/alcohol to -0.11 for general health recommendations. Conclusions: Survivors report an array of concerns ranging from a risk of recurrence (81.4%) to concerns about peripheral neuropathy and lymphedema (51%). Survivors and providers, however, show little concordance concerning recommendations made visits. Provision of personalized survivorship care plans may improve agreement between survivors and providers concerning health recommendations.
Aspartate Beta-Hydroxylase (ASPH) As a Novel Therapeutic Target in Acute Myeloid Leukemia
Authors: Noa G. Holtzman, Michael S. Lebowitz, Rima Koka, Maria R. Baer, Kanam Malhotra, Steven A. Fuller, Amir Shahlaee, Hossein A. Ghanbari, Soren M. Bentzen, Ashkan Emadi
Journal: Blood (2018)
Very High-Risk ASCVD and Eligibility for Nonstatin Therapies Based on the 2018 AHA/ACC Cholesterol Guidelines
Authors: Salim S. Virani, Julia M. Akeroyd, Sidney C. Smith, Mouaz Al-Mallah, Thomas M. Maddox, Pamela B. Morris, Laura A. Petersen, Christie M. Ballantyne, Scott M. Grundy, Neil J. Stone
Journal: Journal of the American College of Cardiology (2019)
Monitoring of circulating tumor cells during systemic therapy allows distinguishing breast cancer patients at risk for relapse
Authors: K. Pachmann, O. Camara, K. Lobodasch, J. Clement, R. Dengler, K. Hoeffken
Journal: Journal of Clinical Oncology (2007)

11006 Background: Recent refinement of methods, allowing detection of minimal numbers of residual cells from malignant tumors have reactivated the debate, to what extent single tumor cells in lymph nodes, bone marrow and peripheral blood can be considered as “micrometastases”. The presence of such cells, indeed, reflects only the first step in the metastatic process, dissemination, and the formation of metastases from such cells seems to be quite ineffective. If, however these cells react to therapy in an identical way as the tumor itself, these cells can be used to monitor therapy response very early during primary systemic (neoadjuvant) therapy, during adjuvant therapy, where no other target is available to control therapy success and already during therapy initiation in metastatic disease. Methods: Circulating epithelial cells were enumerated from 1 ml of anticoagulated blood after red blood cell lysis, staining of live cells with a fluorochrome labeled anti-epithelial antibody and automated microscopy before and after each chemotherapy cycle for monitoring of therapy success. Results: The response of the peripherally circulating cells of 35 patients with breast cancer treated with neoadjuvant chemotherapy varied from marginal (less than tenfold) to highly responsive (more than thousand fold) already during the first three to four courses and showed identical response to therapy as the whole tumor with a correlation of p &gt; 0.9. The method was subsequently applied to monitor the response of such cells in the adjuvant treatment. In the first 25 patients with a follow up of more than 4 years, an increase in cell numbers already from the begin of therapy or following an initial response was observed in 20% of patients and all of these patients have subsequently relapsed (p&lt;0,0001). These results have now been corroborated in a total of 148 patients, confirming a hazard ratio of 25 for relapse in the following 5 years for patients with increasing cell numbers during therapy independent of therapy regimen and a significance of p&lt;0.0001. Conclusions: Quantitative monitoring of circulating tumor cells can be used as a tool for therapy survey in breast cancer in the absence of manifest tumor. No significant financial relationships to disclose.
Excellence in viral hepatitis elimination – Lessons from Georgia
Authors: Francisco Averhoff, Jeffrey V. Lazarus, David Sergeenko, Massimo Colombo, Amiran Gamkrelidze, Tengiz Tsertsvadze, Maia Butsashvili, David Metreveli, Lali Sharvadze, Margaret Hellard, Stefano Gnes, Tamar Gabunia, Muazzam Nasrullah
Journal: Journal of Hepatology (2019)
Genetic alterations in HRAS gene in relation to outcome and response to cetuximab in head and neck squamous cell carcinoma.
Authors: Theodoros Rampias, Athina Giagini, Hiroumi Matsuzaki, Valentina Bartzi, Spyros Siolos, Elena Vaja, Nick Haralambakis, Panagiotis Katsaounis, Andreas Scorilas, Amanda Psyrri
Journal: Journal of Clinical Oncology (2012)

5574 Background: Aberrant signaling through RAS/MAPK pathway is implicated in resistance to EGFR-targeted agents in cancer. Genetic alterations in Hras gene such as mutations and specific polymorphisms are associated with aggressive phenotype in several smoking-related malignancies. We sought to determine the impact of Hras genetic alterations on response to cetuximab and prognosis in HNSCC. Methods: Clinical outcome according to Hras status was investigated in a retrospective cohort of 140 HNSCC specimens. Primary endpoints were overall survival (OS) and disease-free survival (DFS) and secondary endpoint was treatment response. For statistical analysis, T-test was used for continuous data and x2 –test for categorical data. Cetuximab-resistant cell lines harboring mutant Hras (BB49, T24) were infected with lentivirus expressing shRNA targeting the Hras or a scrambled- shRNA. MTT assay was used to determine the effect of cetuximab on growth of lentivirus infected cells. Biochemical analysis involved immunoblotting for pERK1/2. Results: Mutationanalysis of tumor samples showed that 5.7% participants harbored Hras mutations and 16.42% harbored Hras polymorphisms (rs12628, rs41258054) that are associated with tumorigenesis. Patients bearing tumors with mutated Hras had inferior mean OS ( 22.13vs 35.20, p=0.02) and a non-significant trend for inferior mean DFS. Patients with tumors containing Hras genetic alterations (mutation or polymorphism) had significantly inferior mean OS (p=0.02) compared to those harboring wt Hras and trended towards inferior DFS (p=0.07). Patients had received various treatments such as surgery plus/minus RT and various chemotherapy regimens. A subgroup analysis of 38 patients treated with cetuximab-based regimens showed that wt Hras was associated with higher likelihood of attaining CR or PR to treatment of borderline significance (p=0.06) due to small sample size. Silencing of Hras in Hras-mutant cell lines restored sensitivity to cetuximab and caused a direct downregulation of pERK1/2 levels. Conclusions: Hras genetic alterations are associated with aggressive clinical course and may affect response to cetuximab in HNSCC.
Bayesian Estimation of Past Population Dynamics in BEAST 1.10 Using the Skygrid Coalescent Model
Authors: Verity Hill, Guy Baele
Journal: Molecular Biology and Evolution (2019)

Inferring past population dynamics over time from heterochronous molecular sequence data is often achieved using the Bayesian Skygrid model, a nonparametric coalescent model that estimates the effective population size over time. Available in BEAST, a cross-platform program for Bayesian analysis of molecular sequences using Markov chain Monte Carlo, this coalescent model is often estimated in conjunction with a molecular clock model to produce time-stamped phylogenetic trees. We here provide a practical guide to using BEAST and its accompanying applications for the purpose of drawing inference under these models. We focus on best practices, potential pitfalls, and recommendations that can be generalized to other software packages for Bayesian inference. This protocol shows how to use TempEst, BEAUti, and BEAST 1.10 (http://beast.community/; last accessed July 29, 2019), LogCombiner as well as Tracer in a complete workflow.
Andrew John Armour
Authors: Glenn Armour
Journal: BMJ (2019)

Andrew John Armour (“Sandy”) died peacefully at home in Woodhall Spa, Lincolnshire, on 29 June 2019 at the age of 87. For the past two and a half years he had had heart failure, which he bore with stoicism, tenacity, and a remarkable cheerfulness. During this time he had received excellent treatment and nursing from his wife, Ann, the Tasburgh Lodge practice, and a dedicated team of carers.

Sandy was born on 5 September 1931 in Lincoln, the second son of Dr George and Mrs Freda Armour; his elder brother had died soon after his birth. He was educated at St Hugh’s School in Woodhall Spa and was among the cohort—along with his brother, Iain—that was evacuated to Ingleton, north Yorkshire, for their safety during the second world war. Iain still clearly remembers the caring support Sandy gave him after this event and also on train journeys when they were squeezed on to packed troop trains.

Unfortunately, during the summer holidays of 1943, on August 17 a fateful wind carried two parachute mines from the direction of Haltham, one of which destroyed the Royal Hydro Hotel (which stood on the present day Royal Square), resulting in two fatalities. The other landed in the garden of the original Tasburgh Lodge, where the local surgery now is, devastating the building and trapping Sandy, his brother, and their grievously injured mother. It is difficult to imagine the emotional impact on two young boys, aged 11 and 9, as they waited with their injured parent to be rescued from the ruins of their home, which might collapse at any moment. The bench on which they endured …
A prospective evaluation of pegylated interferon alfa-2a therapy in patients with polycythemia vera and essential thrombocythemia with a prior splanchnic vein thrombosis
Authors: J. Mascarenhas, H. Kosiorek, J. Prchal, A. Yacoub, D. Berenzon, M. R. Baer, E. Ritchie, R. T. Silver, C. Kessler, E. Winton, M. C. Finazzi, A. Rambaldi, A. M. Vannucchi, D. Leibowitz, D. Rondelli, M. O. Arcasoy, R. Catchatourian, J. Vadakara, V. Rosti, E. Hexner, M. Kremyanskaya, L. Sandy, J. Tripodi, V. Najfeld, N. Farnoud, M. E. Salama, R. S. Weinberg, R. Rampal, J. D. Goldberg, R. Mesa, A. C. Dueck, R. Hoffman
Journal: Leukemia (2019)