tbuckley/cabot-search huggingface dataset:
Abstract B01: Association of cholangiocarcinoma and hepatocellular carcinoma: Which one should be treated?
Authors: Khaoula Mazouzi
Journal: Cancer Research (2017)

Abstract Introduction: The combination of cholangiocarcinoma and hepatocellular carcinoma is a rare entity. Methods: We will present a clinical case involving a combination of cholangiocarcinoma and hepatocellular carcinoma in a patient with post-viral C cirrhosis. Results: A 60 Y.O male know with a personal history of hepatitis treated in 1969 by an unknown injectable treatment for two years, was presented at the consultation for evolving abdominal bloating. CT-scan revealed ascites with a total portal vein thrombosis and a heterogeneous tumor occupying the right liver without “wash-out” sign. The patient was put under anticoagulation with LMWH. After a week, liver MRI found that the ascites has totally dried, the thrombosis disappeared, and revealed that the tumor had a typical aspect of cholangiocarcinoma. Alfa-fetal protein test was to 1156 IU / ml. Liver biopsy was contradictory; on some pieces hepatocellular carcinoma was found and on others cholangiocarcinoma. Because Sorafenib is a multikinase inhibitor with anti-angiogenic and anti-proliferative action it can be effective on many tumors as they use the same ligands and signaling pathways similar to proliferate, it was chosen instead of chemotherapy at 400 mg/day. Sure enough, after two weeks of treatment, alfa fetoprotein decreased to 834 IU/ml and after two months biology and imaging found a satisfactory partial response. Currently, after six months of treatment, the patient is in complete clinical, biological and radiological remission except that the treatment cannot be interrupted for the time. Surgeons are discussing a partial surgery to the residual liver retraction. Conclusion: This association is rare and needs deep research especially molecular testing for patients who have a spectacular response. Citation Format: Khaoula Mazouzi. Association of cholangiocarcinoma and hepatocellular carcinoma: Which one should be treated? [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B01.
Cardiorespiratory health effects of particulate ambient air pollution exposure in low-income and middle-income countries: a systematic review and meta-analysis
Authors: Katherine Newell, Christiana Kartsonaki, Kin Bong Hubert Lam, Om P Kurmi
Journal: The Lancet Planetary Health (2017)

BackgroundMost prospective studies on the health effects of particulate ambient air pollution exposure have focused on high-income countries, which have much lower pollutant concentrations than low-income and middle-income countries (LMICs) and different sources of pollution. We aimed to investigate the cardiorespiratory health effects of particulate ambient air pollution exposure in LMICs exclusively.MethodsFor this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, LILACS, Global Health, and Proquest for studies published between database inception and Nov 28, 2016, investigating the cardiorespiratory health effects of particulate ambient air pollution exposure in LMICs. Data were extracted from published studies by one author, and then checked and verified by all authors independently. We pooled estimates by pollutant type (particulate matter with a diameter of <2·5 μm [PM2·5] or 2·5–10 μm [PM10]), lag, and outcome, and presented them as excess relative risk per 10 μg/m3 increase in particulate ambient air pollution. We used a random-effects model to derive overall excess risk. The study protocol is registered with PROSPERO, number CRD42016051733.FindingsOf 1553 studies identified, 91 met the full eligibility criteria. Only four long-term exposure studies from China were identified and not included in the meta-analysis. A 10 μg/m3 increase in same-day PM2·5 was associated with a 0·47% (95% CI 0·34–0·61) increase in cardiovascular mortality and a 0·57% (0·28–0·86) increase in respiratory mortality. A 10 μg/m3 increase in same-day PM10 was associated with a 0·27% (0·11–0·44) increase in cardiovascular mortality and a 0·56% (0·24–0·87) increase in respiratory mortality.InterpretationShort-term exposure to particulate ambient air pollution is associated with increases in cardiorespiratory morbidity and mortality in LMIC's, with apparent regional-specific variations.FundingNone.
Antibody Tumor Targeting Is Enhanced by CD27 Agonists through Myeloid Recruitment
Authors: Anna H. Turaj, Khiyam Hussain, Kerry L. Cox, Matthew J.J. Rose-Zerilli, James Testa, Lekh N. Dahal, H.T. Claude Chan, Sonya James, Vikki L. Field, Matthew J. Carter, Hyung J. Kim, Jonathan J. West, Lawrence J. Thomas, Li-Zhen He, Tibor Keler, Peter W.M. Johnson, Aymen Al-Shamkhani, Stephen M. Thirdborough, Stephen A. Beers, Mark S. Cragg, Martin J. Glennie, Sean H. Lim
Journal: Cancer Cell (2017)

Monoclonal antibodies (mAbs) can destroy tumors by recruiting effectors such as myeloid cells, or targeting immunomodulatory receptors to promote cytotoxic T cell responses. Here, we examined the therapeutic potential of combining a direct tumor-targeting mAb, anti-CD20, with an extended panel of immunomodulatory mAbs. Only the anti-CD27/CD20 combination provided cures. This was apparent in multiple lymphoma models, including huCD27 transgenic mice using the anti-huCD27, varlilumab. Detailed mechanistic analysis using single-cell RNA sequencing demonstrated that anti-CD27 stimulated CD8+ T and natural killer cells to release myeloid chemo-attractants and interferon gamma, to elicit myeloid infiltration and macrophage activation. This study demonstrates the therapeutic advantage of using an immunomodulatory mAb to regulate lymphoid cells, which then recruit and activate myeloid cells for enhanced killing of mAb-opsonized tumors.
Phase I/II study of neoadjuvant eribulin mesylate, carboplatin, and trastuzumab (ECH) for operable HER2 positive (HER2+) breast cancer.
Authors: Lee Steven Schwartzberg, Kurt W. Tauer, Robert C. Hermann, Petros G. Nikolinakos, Arthur C. Houts
Journal: Journal of Clinical Oncology (2014)

604^ Background: Docetaxel, carboplatin (C) and trastuzumab (H) yields substantial pathologic complete response (pCR) in operable HER2+ breast cancer (BC). Eribulin mesylate (E) is a tubulin inhibitor shown to improve overall survival in pretreated advanced BC. This Phase I trial was designed to determine the maximum tolerated dose (MTD) of ECH as neoadjuvant therapy in HER2+ BC with a planned follow-on Phase II component with pCR as the primary endpoint. Methods: This was a multicenter open-label single arm trial. Eligible patients (pts) had operable stage IIA – IIIB HER2+ BC, ECOG 0-1, normal LVEF, QTc < 480 msec, < grade 1 neuropathy and no history of invasive cancer within 3 years. Phase I planned up to 18 pts to 1 of 3 E dose cohorts, with pts treated at the MTD also evaluable for the Phase II extension. Starting dose of E was 1.1 mg/m2 with escalation to dose level +1 at 1.4 mg/m2. ECH was given IV for six 3-week cycles with E d1 and d8; C AUC 6 d1; and H 8mg/kg loading dose d1c1 and 6mg/kg d1c2-c6. C1 dose limiting toxicities (DLTs) were defined as: grade 4 thrombocytopenia (TP), anemia, or neutropenia (N) lasting > 5 days; any grade 3-4 non-hematologic toxicity attributable to E, C, H, or the combination; or inability to deliver all three agents at assigned dose and schedule during cycle 1. Standard 3+3 dose escalation design was used. Results: 5/6 patients at 1.1 mg/m2 and 4/6 at 1.4 mg/m2 completed 6 cycles of ECH. The MTD of ECH was not determined. At 1.1 mg/m2 E, Grade 3/4 hematologic toxicity: anemia 4 pts, TP in 2 pts, and N 4 pts, and at 1.4 mg/m2 E, anemia 1 pt, TP in 2 pts and N in 5 pts. 8 of 12 (67%) pts required PRBC transfusions (range 2-12 units) and 2 pts required platelet transfusions (range, 4-12 units). 11 of 12 (92%) pts required dose reduction of E. At surgery, 10 pts (83.3%) achieved partial response and 2 (16.7%) had pCR. Conclusions: In this Phase I study, the ECH regimen was associated with levels of hematologic toxicities and transfusion requirements not observed in other eribulin-carboplatin studies. This combination is not planned to undergo further Phase II development in the HER2+ neoadjuvant setting. Clinical trial information: NCT01388647.
Phase 1/2 study of forodesine in patients with relapsed peripheral t-cell lymphoma (PTCL).
Authors: Kunihiro Tsukasaki, Kensei Tobinai, Toshiki Uchida, Yoshinobu Maeda, Hirohiko Shibayama, Hirokazu Nagai, Mitsutoshi Kurosawa, Yasunobu Abe, Kiyohiko Hatake, Kiyoshi Ando, Isao Yoshida, Michihiro Hidaka, Tohru Murayama, Yoko Okitsu, Norifumi Tsukamoto, Masafumi Taniwaki, Junji Suzumiya, Kazuo Tamura, Takahiro Yamauchi, Ryuzo Ueda
Journal: Journal of Clinical Oncology (2016)

7542 Background: Forodesine, a potent purine nucleoside phosphorylase inhibitor, induces apoptosis mainly in T cells. Forodesine at relatively low dose was feasible but the response rate was not sufficient in early trials for PTCL and cutaneous T-cell lymphomas. A pivotal single-arm phase 1/2 study of forodesine at relatively high dose was conducted in patients with relapsed PTCL. Methods: Eligible patients, who had relapsed PTCL, confirmed by central pathology review according to the WHO classification 2008, and without major organ dysfunction, received forodesine 300 mg twice a day (BID) continuously. Tumor response was assessed with CT and PET by independent imaging review using IWC 2007 criteria. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results: In the phase 1 part (n = 4), no DLTs were observed at 300 mg BID, determined as the recommended phase 2 dose. In the phase 2 part, 44 patients (median age 69; median number of previous treatment 2, range 1-9) received forodesine. The ORR in 41 evaluable patients was 22% (9 of 41; 90% CI 12.0-35.3) including 4 CR (10%) and 5 PR (12%), the lower limit of the 90% CI exceeded 10% threshold. Median PFS and OS were 2.0 and 14.5 months, respectively. The median time to response in 9 responders was 1.9 months (range 1.8-5.5) with median response duration not reached. The most common adverse events (AEs) ( ≥ G3) were lymphopenia (96%), leukopenia (42%), neutropenia (33%), thrombocytopenia (25%), and anemia (20%). Four patients (3 AITLs and 1 PTCL-NOS) developed secondary B-cell non-Hodgkin lymphomas (B-NHL), and one of them died of B-NHL and PD. Two patients developed peripheral neuropathy/myopathy of G3. At the point of data cut-off, among 44 subjects, treatment was discontinued in 37 [PD 30 (81%), AEs 4 (11%), and others 3 (8%)]. Conclusions: Forodesine at 300 mg BID appears to show better efficacy than that in the lower dose previous trial for relapsedPTCL despite some infections and secondary lymphomas possibly associated with lymphopenia. Forodesine would contribute as one of the reasonable options for the treatment of relapsed PTCL. Clinical trial information: NCT01776411.
Association Between Hospital Financial Distress and Immediate Breast Reconstruction Surgery After Mastectomy Among Women With Ductal Carcinoma In Situ
Authors: Catherine A. Richards, Andrew G. Rundle, Jason D. Wright, Dawn L. Hershman
Journal: JAMA Surgery (2017)

<h3>Importance</h3> Hospital financial distress (HFD) is a state in which a hospital is at risk of closure because of its financial condition. Hospital financial distress may reduce the services a hospital can offer, particularly unprofitable ones. Few studies have assessed the association of HFD with quality of care. <h3>Objective</h3> To examine the association between HFD and receipt of immediate breast reconstruction surgery after mastectomy among women diagnosed with ductal carcinoma in situ (DCIS). <h3>Design, Setting, and Participants</h3> This retrospective cohort study assessed data from the Nationwide Inpatient Sample of 5760 women older than 18 years (mean [SD] age: 57.5 [13.2]) with DCIS who underwent mastectomy in 2008-2012 at hospitals categorized by financial distress. Women treated at 1156 hospitals located in 538 different counties across Arkansas, Arizona, California, Colorado, Connecticut, Florida, Iowa, Kentucky, Massachusetts, Maryland, Missouri, North Carolina, New Hampshire, New Jersey, Nevada, New York, Oregon, Pennsylvania, Rhode Island, Utah, Virginia, Vermont, Washington, Wisconsin, West Virginia, and Wyoming were included. Of these, 2385 women (41.4%) underwent immediate breast reconstruction surgery. Women with invasive cancer were excluded. The database included unique hospital identification variables, and participants were identified using<i>International Classification of Diseases, Ninth Revision, Clinical Modification</i>codes. Data were analyzed from January 1, 2012, to February 28, 2014. <h3>Main Outcomes and Measures</h3> The primary outcome was the adjusted association between HFD and receipt of immediate breast reconstruction surgery after mastectomy. <h3>Results</h3> In this analysis of database information, 2385 of 5760 women (41.4%) received immediate breast reconstruction surgery. Of these, 693 (36.7%) were treated at a hospital under high HFD and received immediate breast reconstruction surgery compared with 863 (44.0%) treated at a hospital under low HFD (<i>P</i> &lt; .001). Reconstruction surgery was associated with younger age, white race, private insurance, treatment at a teaching and cancer hospital, private hospital ownership, and the percentage of individuals in the county with insurance. After adjustment, women treated at hospitals under high HFD (OR, 0.79; 95% CI, 0.62-0.99) and medium HFD (OR, 0.76; 95% CI, 0.61-0.94) were significantly less likely to receive reconstruction than women treated at hospitals with low to no HFD. <h3>Conclusions and Relevance</h3> The financial strength of the hospital where a patient receives treatment is associated with receipt of immediate breast reconstruction surgery. In addition to focusing on patient-related factors, efforts to improve quality should also focus on hospital-related factors.
Abstract 17008: Increased Cost of Cardiac Surgery in Frail Compared to Non-frail Older Adults
Authors: Michael Goldfarb, Melissa Bendayan, Lawrence Rudski, Jean-Francois Morin, Yves Langlois, Felix Ma, James Brophy, Jonathan Afilalo
Journal: Circulation (2016)

Introduction: While frailty is now well established as a risk factor for mortality and morbidity after cardiac surgery, its role as a determinant of hospital costs has yet to be elucidated. Methods...
A degradation fragment of type X collagen is a real-time marker for bone growth velocity
Authors: Ryan F. Coghlan, Jon A. Oberdorf, Susan Sienko, Michael D. Aiona, Bruce A. Boston, Kara J. Connelly, Chelsea Bahney, Jeremie LaRouche, Sarah M. Almubarak, Daniel T. Coleman, Irute Girkontaite, Klaus von der Mark, Gregory P. Lunstrum, William A. Horton
Journal: Science Translational Medicine (2017)

A type X collagen fragment derived from endochondral ossification and detected in blood is a marker for growth velocity.
Of pools, oceans, and the Dead Sea
Authors: Samir K. Ballas
Journal: Blood (2017)

a Wee1 inhibitor, representing a synthetic lethal approach. 10However, in the AML model, RRM2 levels were unchanged, again pointing to potentially indirect and cell type-specific effects of SETD2 loss on gene expression conceivably through nonchromatin mechanisms, such as modification of transcription factor activity.With a genetically faithful model of SETD2-associated malignancy in hand, further screens for vulnerabilities using gene editing are warranted.Thorough analysis of these mice for changes in gene expression and chromatin modifications, p53 target expression, and interferon pathways may lead to further clues to the aggressive biology generated by SETD2 loss.
Substantial atherosclerotic celiac axis stenosis is a new risk factor for biliary fistula after pancreaticoduodenectomy
Authors: Yiran Zhou, Wei Wang, Yusheng Shi, Xiongxiong Lu, Qian Zhan, Hao Chen, Xiaxing Deng, Chenghong Peng, Baiyong Shen
Journal: International Journal of Surgery (2017)
Cografting astrocytes improves cell therapeutic outcomes in a Parkinson’s disease model
Authors: Jae-Jin Song, Sang-Min Oh, Oh-Chan Kwon, Noviana Wulansari, Hyun-Seob Lee, Mi-Yoon Chang, Eunsoo Lee, Woong Sun, Sang-Eun Lee, Sunghoe Chang, Heeyoung An, C. Justin Lee, Sang-Hun Lee
Journal: Journal of Clinical Investigation (2017)

Transplantation of neural progenitor cells (NPCs) is a potential therapy for treating neurodegenerative disorders, but this approach has faced many challenges and limited success, primarily because of inhospitable host brain environments that interfere with enriched neuron engraftment and function. Astrocytes play neurotrophic roles in the developing and adult brain, making them potential candidates for helping with modification of hostile brain environments. In this study, we examined whether astrocytic function could be utilized to overcome the current limitations of cell-based therapies in a murine model of Parkinson's disease (PD) that is characterized by dopamine (DA) neuron degeneration in the midbrain. We show here that cografting astrocytes, especially those derived from the midbrain, remarkably enhanced NPC-based cell therapeutic outcomes along with robust DA neuron engraftment in PD rats for at least 6 months after transplantation. We further show that engineering of donor astrocytes with Nurr1 and Foxa2, transcription factors that were recently reported to polarize harmful immunogenic glia into the neuroprotective form, further promoted the neurotrophic actions of grafted astrocytes in the cell therapeutic approach. Collectively, these findings suggest that cografting astrocytes could be a potential strategy for successful cell therapeutic outcomes in neurodegenerative disorders.
Postpartum Hemolytic Uremic Syndrome
Authors: D. B. Gould
Journal: JAMA (1982)

<h3>To the Editor.—</h3> I must submit an objection to the advocacy of the article by Spencer et al. The most immediate criticism of the analysis of efficacy of these plasma-exchange transfusion interventions is the post hoc propter hoc fallacy. Why did the initial plasma infusions "not appear to be of benefit," while subsequent plasma exchange coincide with improvement? The parturient woman in question recovered from her illness because the factor that incited her acute renal failure was eliminated— the pregnancy was terminated. Short of the development of renal cortical necrosis, her eventual full recovery of renal function was ensured. Moreover, the correct renal disorder needs to be identified. The kidney disorder that befell this "preeclamptic patient" was the basic glomerular compromise of systemic paracoagulation, for which women with hypertensive disorders of pregnancy are at risk. Additionally, she was found to have an abrupted placenta, a major cause of the same
Saint John Dictating to the Venerable Bede
Authors: M. Therese Southgate
Journal: JAMA (1980)

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Proposals for opt-out organ donation launched for England
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The Department of Health has launched a consultation1 on how to implement an opt-out system of organ donation in England.

The move, which the government hopes will increase the number of organ donations, follows a pledge made by the prime minister Theresa May at the Conservative Party conference in October.2

The plans could lead to the law on organ donation being changed in England to presume consent unless people opt out. However, it is unlikely that organs would be taken against the wishes of the patient’s families.

But experts expressed concerns about the focus of the consultation, and urged …
Results from a phase 1b/2 study of RX-0201, a novel AKT-1 antisense, combined with everolimus to treat metastatic clear cell renal carcinoma.
Authors: Neeraj Agarwal, Scott T. Tagawa, Gurkamal S. Chatta, Sumanta K. Pal, Sanjay Goel, Reza Mazhari, Callie Heaton, Ely Benaim
Journal: Journal of Clinical Oncology (2016)

2559 Background: RX-0201 is a novel, oligonucleotide that binds native AKT-1 mRNA, preventing downstream phosphorylation to p-AKT. RX-0201, in combination with everolimus, to treat metastatic clear cell renal carcinoma. In vitro RX-0201, in combination with everolimus, additively inhibited Caki-1 cell growth. Methods: The Phase 1b/2 proof-of-concept, multicenter, open label study is conducted in 2 stages (NCT02089334). Stage 1 is a dose-escalation Phase 1b/2 study of RX-0201 in combination with everolimus (10 mg daily). RX-0201 was given as a continuous intravenous infusion for 14 days followed by 7 days of rest. Subjects were enrolled at increasing doses of RX-0201 in a 3+3 design. The target dose of RX-0201 identified in Stage 1 is being studied further evaluated in Stage 2, which is a randomized, 2-arm study of RX-0201 in combination with everolimus versus everolimus alone. Plasma concentrations were measured in Stage 1 and noncompartmental pharmacokinetic parameters were calculated using WinNonlin, Version 6.4. Results: In Stage 1 of the Phase 1b study, subjects were treated with 125 mg/m2/day (n = 3), 200 mg/m2/day (n = 4), and 250 mg/m2/day (n = 3) RX-0201 in combination with 10 mg everolimus. Seven males and three females, median age 61 years, were treated. Subjects received 1-3 treatments prior to study entry (median = 1). The most common toxicities attributed to the combination were rash, mouth ulceration, decreased weight, thrombocytopenia, facial edema, fatigue, and pruritus. No significant events were attributed to RX-0201 alone. Most events (81%) were mild or moderate in severity. Based on the tolerability, 250 mg/m2/day RX-0201 dose was declared the recommended Stage 2 dose. Four subjects in the Stage 1 of Phase 1b study have experienced stable disease for 383, 191, 129 and 58 days; also a tumor burden reduction from 16% to 38.5% was seen in four subjects. RX-0201 PK demonstrated a dose proportional exposure. Conclusions: RX-0201, in combination with everolimus, appears to be safe and well tolerated in patients with metastatic renal cancer at doses up to 250 mg/m2/day. Stage 2 of the Phase 1b/2 clinical study is currently ongoing. Clinical trial information: NCT02089334.
Is the PET/CT first choice for differential diagnosis of fever of FUO/IUO?
Authors: Berkan Armagan, Abdulsamet Erden, Ozlem Beydas, Alper Sari, Levent Kilic, Umut Kalyoncu
Journal: Annals of the Rheumatic Diseases (2017)

First, thanks for this interesting article that tries to answer a difficult clinical problem of patients with fever of unknown origin (FUO) and inflammation of unknown origin (IUO) who are discharged without diagnosis.1 

This study is very important in creating a diagnostic algorithm for FUO and IUO. We wanted to address some of the …