tbuckley/cabot-search huggingface dataset:
Clinical and Laboratory Features of 103 Patients From 42 Italian Families with Inherited Thrombocytopenia Derived From the Monoallelic Ala156Val Mutation of GPIb Alpha (Bolzano Mutation)
Authors: Carlo Luigi Balduini, Silverio Perrotta, Roberta Bottega, Alessandro Pecci, Federica Melazzini, Elisa Civaschi, Sabina Russo, Silvana Magrin, Giuseppe Loffredo, Veronica Di Salvo, Giovanna Russo, Maddalena Casale, Daniela De Rocco, Claudio Grignani, Marco Cattaneo, Carlo Baronci, Alfredo Dragani, Veronica Albano, Momcilo Jankovic, Saverio Scianguetta, Anna Savoia, Patrizia Noris
Journal: Blood (2011)
The relationship between age and survival outcomes for eribulin in metastatic breast cancer.
Authors: C. Twelves, L. T. Vahdat, J. Cortes, J. Wanders, C. E. Dutcus, S. Seegobin, H. B. Muss
Journal: Journal of Clinical Oncology (2011)

1060 Background: Metastatic breast cancer (mBC) is common in older patients (pts) with treatment often complicated by comorbidities-resulting in increased toxicity from chemotherapy and sub-optimal therapy if treatment is inappropriately modified. The phase III EMBRACE trial showed significant improvement on overall survival (OS) for eribulin mesylate monotherapy compared to common chemotherapy agents used in the 3rd-line mBC setting. We sought to compare the benefits and toxicities of eribulin in older and younger pts. Methods: In this exploratory analysis, OS, progression-free survival (PFS), overall response rate (OR; PR+CR), clinical benefit rate (CBR; PR+CR+SD for >6 mos) and toxicity of eribulin-treated pts were compared in 4 age cohorts. Age was fitted as a categorical covariate in a cox proportional hazard model for OS and PFS, and as an interaction term for the Cochran-Mantel-Haenszel test to assess ORR and CBR. Analyses were stratified by geographic region, HER2/neu status, and prior capecitabine use. A further sensitivity analysis of OS fitted age as a continuous covariate with similar stratification to the primary analysis. Results: A total of 508 pts received eribulin in the EMBRACE trial-mean age (SD), 54.8 (10.3); range 28−85. Median OS trended inversely with age; however, this effect was non-significant when fitted as a categorical (Log Rank Test, p=0.40) or continuous covariate (p=0.10). Examination of secondary endpoints yielded a similar, non-significant trend-PFS (p=0.36), ORR (p=0.25), and CBR (p=0.96). The rate of grade 3/4 adverse events did not differ significantly across the age groups-neutropenia, 36.9%;50.3%; febrile neutropenia, 3.9%;5.0%; and neuropathy, 0.6%,4.5%. Treatment withdrawal rates did not differ between age groups. Conclusions: This analysis, while in a limited number of older pts, suggests survival outcomes with eribulin are independent of age; importantly, toxicity appears no greater in older pts. Age alone should not preclude the consideration of eribulin for older pts. ITT population REP population Age at recruitment N OS (mos) PFS (mos) N ORR CBR <50 161 11.8 3.5 146 14.4 21.9 50-59 174 13.6 3.7 157 14.7 24.2 60-69 129 13.8 3.8 123 8.1 22.0 >70 44 14.2 4.2 42 7.1 21.4 Abbreviations: REP, response evaluable population.
Telomere length and pancreatic cancer risk: breaking down the evidence
Authors: Eric J Duell
Journal: Gut (2016)

Telomeres, located at the ends of chromosomes and composed of a protein complex and tandem repeats of TTAGGG nucleotides, function to protect chromosomes from end-to-end fusions, breakage and degradation in dividing cells. Due to the inherent nature of DNA replication (‘the end replication problem’) and oxidative stress—telomeres gradually shorten with age. This has been demonstrated cross-sectionally in most tissues examined including the pancreas, and especially in cells with extensive proliferation (eg, leucocytes).1 ,2 Cells with critically short telomeres enter growth arrest, or senescence, and may remain viable for extended periods. Premalignant cells can avoid senescence and continue to proliferate by upregulating telomerase or elongating telomeres by alternative mechanisms.1

Shortened telomeres are thought to contribute to chromosomal instability and age-related diseases in humans, including cancer. Up to 90% of human tumours reactivate telomerase, which is epigenetically silenced in most adult somatic cells.1 Somatic promoter mutations and germ-line sequence variants at TERT (the gene that encodes the catalytic subunit of telomerase reverse transcriptase on chr 5p15.33) have been observed in various human cancers, indicating extensive pleiotropy at this locus.3 Although somatic mutations in TERT are uncommon in pancreatic cancer (PC), several independent PC risk loci marked by common (and less common) susceptibility alleles have been (and likely will continue to be) identified at the …
Adverse Events Following Infusion of T Cells for Adoptive Immunotherapy: A 10 Year Experience.
Authors: Conrad Russell Y. Cruz, Patrick Hanley, Hao Liu, Vicky Torrano, Yu-Feng Lin, Stephen Gottschalk, Barbara Savoldo, Gianpietro Dotti, Chrystal Louis, Ann M. Leen, Cliona M. Rooney, Adrian P. Gee, Malcolm K. Brenner, Catherine M. Bollard, Helen E. Heslop
Journal: Blood (2009)
Single fraction high-dose-rate brachytherapy and hypofractionated external beam radiation therapy in the treatment of intermediate-risk prostate cancer: Long-term results.
Authors: F. L. Cury, M. Duclos, A. G. Aprikian, H. Patrocinio, W. Kassouf, G. Shenouda, S. Faria, M. David, L. Souhami
Journal: Journal of Clinical Oncology (2011)

83 Background: We present the long-term results of a cohort of patients with intermediate-risk prostate cancer (PC) treated with single fraction high-dose-rate brachytherapy (HDRB) combined with hypofractionated external beam radiation therapy (HRT). Methods: Patients with intermediate-risk PC were treated exclusively with HDRB and HRT. HDRB delivered a dose of 10 Gy to the prostate gland and HRT consisted of 50 Gy delivered in 20 daily fractions. The planning target volume was the prostate gland with a 1 cm margin all around. The first 121 consecutive patients with a minimum of 2 years post-treatment follow-up were assessed for acute and chronic toxicity and disease control. Results: The median follow-up was 62.8 months. No acute grade III or higher toxicities were seen. Grade II late GI toxicity was seen in 9 patients (7.4%) and grade III in 2 (1.6%). Grade 3 GU toxicity was seen in 2 patients (1.6%), both with urinary obstructive symptoms requiring catheterization. A repeat biopsy was offered to the first 58 consecutively treated patients, and 44 patients agreed with the procedure. A negative biopsy was found in 40 patients (91%). The biochemical relapse-free survival rate at 5 and 8 years were 90.7% and 81.4%, with 13 patients presenting biochemical failure. Among them, nine were diagnosed with distant metastasis. Prostate cancer-specific and overall survival rates at 8 years were 100% and 95.5%, respectively. Conclusions: Our program of HDRB and HRT is well tolerated, with acceptable toxicity rates. Furthermore, results from re-biopsies revealed an elevated rate of local control. These results are encouraging and confirm that the use of conformal RT techniques, adapted to specific biological features, have the potential to improve the therapeutic ratio in intermediate risk PC patients. No significant financial relationships to disclose.
Comorbidity and sorafenib (SOR) therapy in elderly patients with metastatic renal cell carcinoma (mRCC).
Authors: A. Gernone, A. Pagliarulo, V. Pagliarulo
Journal: Journal of Clinical Oncology (2011)

398 Background: SOR is a multikinase inhibitor with activity in mRCC. Older patients (pts) benefit from SOR as reported in the subgroup analysis of the TARGET study populations. We evaluated the efficacy and safety in elderly pts (≥ 70) with comorbidities. Methods: A comprehensive geriatric assessment (CGA) was used in older mRCC pts. From 2007 to 2010, 30 pts (23 males and 7 females) received SOR 400 mg BID continuous dosing. Comorbidities were evaluated using the cumulative illness rating scale for geriatrics (CIRS-G). The total score was 0–4. 10 pts with CIRS-G 1, 12 pts with CIRS-G 2, 8 pts with CIRS-G 3/4. Median age was 76 (70–84), ECOG PS 0–2, 24/30 had undergone prior nephrectomy. The most frequent comorbidities were arrhythmias, hypertension, chronic bronchitis, diabetes mellitus, neurological disease. The endpoints were response rate (RR) evaluated by RECIST criteria and correlations between comorbidities and toxicity. Results: Dose reduction (400–600 mg/die) were required for pts with CIRS-G 3–4. No correlations were found between comorbidities (CIRS-G) and response to SOR. 18 pts (14 pts CIRS-G 1/2, 4 pts CIRSG 3/4) had partial response (PR)with a duration of 24 months (9-30) and 12 pts (8 pts CIRS-G 1-2, 4 pts CIRS-G 3/4) stable disease (SD) for 24 months (7–32). 17/30 pts (12 pts CIRS-G 1/2, 5 pts CIRS-G 5) remain on therapy. Drug related adverse events were mainly grade 1 and 2 and were medically manageable. 4 pts required dose interruption (3 pts CIRS-G 1/2, 1 pt CIRS-G 3/4). Pts with CIRS-G score 3–4 had poorer quality of life but the clinical benefit achieved with SOR therapy was high. Conclusions: Comorbidities in pts with mRCC ≥ 70 years did not result in increased incidence of toxicity on SOR treatment. These data suggest that SOR is effective and safe in elderly pts with an overall clinical benefit rate (PR + DS) particularly high. No significant financial relationships to disclose.
Temporally Distinct Developmental Waves of Erythropoiesis from Human Pluripotent Stem Cells
Authors: Orna Steinberg Shemer, Marta Byrska-Bishop, Jacob C Ulirsch, Osheiza Abdulmalik, Yu Yao, Ah Ram Kim, Paul Gadue, Paul D. Kingsley, Deborah French, Ross C. Hardison, James Palis, Vijay G Sankaran, Mitchell J Weiss
Journal: Blood (2015)
Gene Expression Profiling Identifies the JAK/STAT and NFκB Pathways to Be Important in Peripheral T-Cell Lymphomas and Natural-Killer T-Cell Lymphomas
Authors: Tiffany Tang, George Allen, Ghee Chong Koo, Kevin Tay, Daryl Tan, Richard Quek, Miriam Tao, Soo Yong Tan, Bin Tean Teh, Soon Thye Lim
Journal: Blood (2011)
Subcutaneous Injection Of Bortezomib, Combined With Doxorubicin and Dexamethasone (sPAD) Is Effective and Safety Induction Therapy For Untreated Multiple Myeloma Patients
Authors: Naoki Takezako, Naohiro Sekiguchi, Akihisa Nagata, Tsuyoshi Hagino, Satoshi Noto, Kazuhiko Natori, Akiyoshi Miwa
Journal: Blood (2013)
Care transition interventions for children with asthma in the emergency department
Authors: Molly A. Martin, Valerie G. Press, Sharmilee M. Nyenhuis, Jerry A. Krishnan, Kim Erwin, Giselle Mosnaim, Helen Margellos-Anast, S. Margaret Paik, Stacy Ignoffo, Michael McDermott
Journal: Journal of Allergy and Clinical Immunology (2016)
Phase II study of 153-samarium-EDTMP followed by haematopoietic stem cell for patients with osteosarcoma with bone metastasis.
Authors: B. Massimo, G. Grignani, A. Giostra, M. Pagano, S. Ferrari, B. O. Elia, F. Carnevale-Scianca, M. Aglietta, R. E. Pellerito, F. Fagioli
Journal: Journal of Clinical Oncology (2011)

10040 Background: Bone metastatic patients with osteosarcoma have a very poor prognosis. Targeted radiation therapy has been pursued as a valid alternative and 153-Samarium ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) has been investigated as a radiopharmaceutical agent selectively delivering radiation to osteoblastic skeletal lesions (Anderson PM et al. JCO 2002; 20:189-196). Methods: Twenty-two osteosarcoma patients were treated with 153Sm-EDTMP at various dosages. All patients were previously treated with full dose of Cisplatin, Doxorubicin, Metotrexate and Ifosfamide. Seventeen patients had both osseous and extra osseous disease, whilest 5 patients had osseous disease only. Administered activities ranged from 150 (3 mCi/Kg) to 1.140 Mbq/kg (30 mCi/Kg). For all patients, autologous HSC (CD34+>2x106/Kg) infusion was performed on day 14 after the 153Sm-EDTMP infusion. The primary endpoint of this study was the progression free survival (PFS) at 4 months. Results: 153Sm-EDTMP dose level was <10 mCi/kg (<370 MBq/kg) for 6 patients; 10-20 mCi/kg (370-740 MBq/kg) for 9 patients and 20-30 mCi/kg (740-1110 MBq/kg) for 7 patients. The median 24 hours activity was 4.13 mCi/Kg. The median time to recover ANC >0.5x109/L was 10 days (0-37); median time to platelets >50x109/L was 18 days (13-47); median time to Hgb >10 g/dl was 20 days (0-32). One female patient with iliac bone disease (lesion of 7,5 x 5,5 x 5 cm) did not recover until tumor progression and finally died of progressive disease. At day 60 after 153Sm-EDTMP infusion, 10 patients had stable disease and 12 progression. The median PFS was 61 days (18-436) and the median OS was 189 days (31-1175). PFS and OS at 4 months for the entire patient population were 32% (CI 95% 16-50) and 76% (CI 95% 52-89) at 4 months. No statistical differences emerged according to 153Sm-EDTMP administrated dose or 24-h retained activity. Conclusions: Based on our series we can conclude the PFS is dramatically short even when higher dose of 153SmEDTMP are administrated; even at high dose of 153SmEDTMP we can not observe objective response. This translate in no advantage in terms of PFS compared to patients having received lower dose of 153SmEDTMP.
Oral Vancomycin Is Highly Effective in Preventing Clostridium Difficile infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients
Authors: Alex Ganetsky, Jennifer H Han, Mitchell E Hughes, Daria V. Babushok, Noelle V Frey, Saar I Gill, Elizabeth Hexner, Alison Wakoff Loren, Selina Luger, James K Mangan, Jacqueline Smith, Edward A. Stadtmauer, Craig W. Freyer, Cheryl Gilmar, David L Porter
Journal: Blood (2016)
Immunologic markers associated with favorable prognosis in breast cancer patients: Role of innate immune system.
Authors: M. L. Ascierto, M. Kmieciak, M. O. Idowu, D. Bedognetti, A. De Maria, H. D. Bear, E. Wang, F. Marincola, M. Manjili
Journal: Journal of Clinical Oncology (2011)

43 Background: Recognition of tumor cells by NK cells is mediated by the interaction of activating and inhibitory NK cell receptors with ligands expressed on the interacting cell. In addition to inhibitory and activating receptors, NK cells express adhesion molecules that allow conjugate formation between NK cells and their tumor targets. We have recently identified by transcriptional analysis of breast tumor specimens a signature of 5 genes, which included B cell response and interferon signaling, found to predict with &gt; 85% accuracy relapse-free survival. In the current study we analyzed by gene expression profile, whether a differential expression of activatory and inhibitory receptors and gene involved in NK cell-target interactions could be identified in relapse and relapse free patients.Methods: RNA extraction and gene expression analysis was performed on tumor specimens with at least 10% of infiltrating cells deriving from 9 from breast cancer patients who had either 3-7 years relapse-free survival (n=9) or developed tumor relapse within 1-3 years after the initial treatment (n=8). Data were analyzed by BRB tools and Partek software.Results: Our results showed that patients with a favorable prognosis showed increased expression of genes involved in NK interaction with tumor cells and NK activating signaling. In particular an up-regulation of leukocyte function-associated antigen 1 (LFA-1) gene, typically involved in NK cells adhesion to target cells and DNAM 1, usually associated with activation of NK cells and considered one of the major protagonist of NK- Dendritic cells crosstalk, was observed to occur in relapse free patients. In addition, an up regulation of CD96 and CRTAM which, like DNAM 1, promote NK cell-target cell adhesion by interacting with the Necl2 and poliovirus receptor (PVR), was observed in relapse free patients. Conclusions: Our observation suggests that the NK signatures are associated with favorable outcome in breast cancer and allow us to generate new hypothesis on the role of innate immunity in this contest.
Identification of pathogenic macrophages in breast cancer as markers of tumor aggressiveness.
Authors: R. Mukhtar, A. P. Moore, V. Tandon, O. Nseyo, A. Au, F. L. Baehner, C. A. Adisa, N. Eleweke, O. I. Olopade, D. H. Moore, M. Campbell, L. Esserman
Journal: Journal of Clinical Oncology (2011)

1043 Background: Proliferating macrophages (promacs) are considered to be pathologic. We previously reported high promacs in estrogen receptor (ER) negative, high grade breast cancers with early recurrence. Given the technical complexities of double staining for promacs, we tested another macrophage marker associated with tumoral invasion in several cancer types, Mac387. We asked whether or not Mac387 would identify promac-rich tumors with early recurrences, and therefore, be a simpler potential marker to assess the impact of macrophage targeted drugs in breast cancer. Methods: We obtained fixed breast tumor tissue from 367 patients from UCSF, California Pacific Medical Center, Highland Hospital (Oakland, CA), Abia State University (Aba, Nigeria), and Ghana. Immunohistochemical stains for Mac 387 were read by two independent pathologists. Mac387 staining was dichotomized as < or >10% of a high powered field (hpf) and was compared to previously obtained promac counts ( >5 promacs/hpf versus <5 promacs/hpf). We used Stata Version 11 for analysis. Results: Like promacs, high Mac 387 counts were associated with ER negativity (p < 0.001), high tumor grade (p < 0.001), tumor necrosis (p = 0.001), younger age (p = 0.001), and decreased recurrence free survival (RFS, p = 0.04). Concordance between high Mac387 and high promacs was 0.3. 39% of tumors were high for both, 22% were low for both, 6% had low promacs but high Mac 387, and 33% had high promacs but low Mac 387. Those tumors that had both high Mac 387 and high promacs had a stronger association with decreased RFS (p = 0.005, Figure 1). The hazard ratio (HR) for recurrence was 1.7 (p < 0.05, 95% CI 1.01−2.8) among cases with high Mac387; the HR for cases high in both Mac387 and promacs was 1.9 (p = 0.006, 95% CI 1.2−3). Conclusions: Tumors that were high in both Mac387 and promacs had the strongest association with early recurrence. However, Mac387 alone was also significantly associated with shorter RFS with an overlapping 95% CI as the combination, and is simpler to measure. Mac387 may identify a subset of promacs that are key players in promoting breast tumor invasiveness.
Patient factors influencing choice for mastectomy.
Authors: M. R. Hart, A. M. Steely, T. A. James, L. E. McCahill
Journal: Journal of Clinical Oncology (2011)

264 Background: The process of shared decision-making in the surgical management of breast cancer is complex. Many women eligible for breast conservation therapy (BCT) still choose total mastectomy (TM), and little is known about the factors responsible for their decision. We conducted a pilot, qualitative study in order to determine factors influencing the selection of TM over BCT, and to improve our understanding of patient’s concerns and priorities in their decision-making process for breast cancer surgery. Methods: Data were collected from a four-year, prospective Breast Cancer Surgical Quality Database. Study participants included female patients with invasive carcinoma who, despite being eligible for BCT, elected to undergo TM. Eligibility criteria included women with no contraindications to BCT, tumor size &lt;2cm, and no evidence of extensive microcalcifications. Patients with tumor recurrence, multicentric disease, scleroderma, and lupus were excluded. Patients were contacted by phone and administered a survey designed to elicit the specific factors affecting their decision to undergo TM. Results: Out of 670 patients treated for IDC/ILC between 2003 and 2007, 12 met eligibility criteria and were subsequently interviewed. 10 patients identified fear of recurrence as the prevailing factor in their decision to undergo TM, and 5 patients identified availability of breast reconstruction as a moderate to strong influence in their decision to undergo TM. Time away from work and transportation during radiation therapy had minimal or no influence. Conclusions: Our results indicate that patients with small, invasive breast cancers who chose TM for their surgical treatment, despite being eligible for BCT, were primarily influenced by fear of recurrence. These decision factors persisted despite treatment at a multidisciplinary center, where patients are informed of equivalent survival and minimal difference in recurrence with appropriate BCT. These results highlight the need for further assessment of patient education and comprehension, as well as greater awareness of emotional factors which may influence a patient’s decision regarding the surgical management of her breast cancer.
Prevalence and correlates of vaccine hesitancy among general practitioners: a cross-sectional telephone survey in France, April to July 2014
Authors: Pierre Verger, Fanny Collange, Lisa Fressard, Aurélie Bocquier, Arnaud Gautier, Céline Pulcini, Jocelyn Raude, Patrick Peretti-Watel
Journal: Eurosurveillance (2016)

This article sought to estimate the prevalence of vaccine hesitancy (VH) among French general practitioners (GPs) and to study its demographic, professional and personal correlates. We conducted a cross-sectional telephone survey about GPs’ vaccination-related attitudes and practices in 2014 in a national panel of 1,712 GPs in private practice, randomly selected from an exhaustive database of health professionals in France. A cluster analysis of various dimensions of VH (self-reported vaccine recommendations, perceptions of vaccine risks and usefulness) identified three clusters: 86% of GPs (95% confidence interval (CI): 84–88) were not or only slightly vaccine-hesitant, 11% (95% CI: 9–12) moderately hesitant and 3% (95% CI: 3–4) highly hesitant or opposed to vaccination. GPs in the latter two clusters were less frequently vaccinated and reported occasional practice of alternative medicine more often than those in the first cluster; they also described less experience with vaccine-preventable diseases and more experience with patients who they considered had serious adverse effects from vaccination. This study confirms the presence of VH among French GPs but also suggests that its prevalence is moderate. Given GPs’ central role in vaccination, these results nevertheless call for a mobilisation of stakeholders to address VH among GPs.