tbuckley/cabot-search huggingface dataset:
Case 5-1966
Authors: Claude E. Welch, Benjamin Castleman
Journal: New England Journal of Medicine (1966)

Presentation of CaseA fifty-three-year-old woman entered the hospital because of bleeding.She had been well until seven years previously, when she was admitted to another hospital because of pain in the chest; she was told that she had heart disease, and medications of unknown nature were prescribed. Two and a half years before admission dysphasia and right hemiparesis developed, and the patient was almost wholly confined to bed thereafter. Her relatives stated that during the four months before entry she "lost interest in life." For four weeks before admission she ingested little food except for small quantities of milk. . . .
Selective and segmental lysis of the visceral epithelial-cells (vec) leads to increased bulk flow through the capillary wall (cw) causing intracapillary thrombosis resembling the hyalinosis as seen in focal and segmental glomerulosclerosis (fsgs)
Authors: W Laurens, B Vandamme, P Steels, Yves Vanrenterghem
Journal: Kidney International (1993)
Unsafe Use, Knowledge and HCV Infection: Results from a Sero-Behavioral Survey of Current Injectors in Germany
Authors: M. Gassowski, B. Wenz, S. Nielsen, C. Santos-Hövener, U. Marcus, M. An der Heiden, O. Hamouda, V. Bremer, S.R. Ross, C.T. Bock, R. Zimmermann
Journal: Journal of Hepatology (2016)
Safety and Efficacy of IFN&amp;RBV-Free DAA-Based Regimens in HCV-Recurrence after Orthotopic Liver Transplantation
Authors: S. Beinhardt, R. Al-Zoairy, C. Freissmuth, K. Kozbial, R. Stern, A.F. Stättermayer, H. Zoller, A. Maieron, R. Stauber, K. Staufer, M. Strasser, W. Vogel, M. Peck-Radosaljevic, M. Trauner, P. Ferenci, H. Hofer
Journal: Journal of Hepatology (2016)
Rituximab and Chlorambucil as Front-Line Treatment in Untreated Follicular Lymphoma: a Combination with a Durable Response and Low Toxicity Profile.
Authors: Simona Bassi, Luca Nassi, Giancarlo Pruneri, Simona Sammassimo, Paola Bertazzoni, Federica Gigli, Anna Vanazzi, Emilia Cocorocchio, Patrizia Mancuso, Cristina Rabascio, Maria Teresa Lionetti, Daniele Laszlo, Giovanni Martinelli
Journal: Blood (2009)
Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease
Authors: Yaron Rotman, Arun J Sanyal
Journal: Gut (2016)

Given the high prevalence and rising incidence of non-alcoholic fatty liver disease (NAFLD), the absence of approved therapies is striking. Although the mainstay of treatment of NAFLD is weight loss, it is hard to maintain, prompting the need for pharmacotherapy as well. A greater understanding of disease pathogenesis in recent years was followed by development of new classes of medications, as well as potential repurposing of currently available agents. NAFLD therapies target four main pathways. The dominant approach is targeting hepatic fat accumulation and the resultant metabolic stress. Medications in this group include peroxisome proliferator-activator receptor agonists (eg, pioglitazone, elafibranor, saroglitazar), medications targeting the bile acid-farnesoid X receptor axis (obeticholic acid), inhibitors of de novo lipogenesis (aramchol, NDI-010976), incretins (liraglutide) and fibroblast growth factor (FGF)-21 or FGF-19 analogues. A second approach is targeting the oxidative stress, inflammation and injury that follow the metabolic stress. Medications from this group include antioxidants (vitamin E), medications with a target in the tumour necrosis factor α pathway (emricasan, pentoxifylline) and immune modulators (amlexanox, cenicriviroc). A third group has a target in the gut, including antiobesity agents such as orlistat or gut microbiome modulators (IMM-124e, faecal microbial transplant, solithromycin). Finally, as the ongoing injury leads to fibrosis, the harbinger of liver-related morbidity and mortality, antifibrotics (simtuzumab and GR-MD-02) will be an important element of therapy. It is very likely that in the next few years several medications will be available to clinicians treating patients with NAFLD across the entire spectrum of disease.
Coffee and Intestinal Permeability in a Mice Model of Non-Alcoholic Fatty Liver Disease
Authors: G. Mazzone, V. Lembo, G. D’Argenio, P. Vitaglione, A. Rossi, I. Piscosquito, M. Savoia, M. Guido, F. Morisco, N. Caporaso
Journal: Journal of Hepatology (2016)
Outcome, Safety and Tolerability of Treating Hepatitis C in Decompensated Cirrhotics with Ledipasvir/Sofosbuvir with or without Ribavirin or Sofosbuvir with Ribavirin: Real Life Data
Authors: K. Selim, W. Long, B. Elhazin, J. Salazar, M. Karmanova, M. Volk
Journal: Journal of Hepatology (2016)
Deletion of the Protein Tyrosine Phosphatase Gene PTPN2 in T-Cell Acute Lymphoblastic Leukemia.
Authors: Maria Kleppe, Idoya Lahortiga, Tiama El Chaar, Kim De Keersmaecker, Nicole Mentens, Carlos Graux, Katrien Van Roosbroeck, Adolfo A. Ferrando, Anton W Langerak, Jules P.P. Meijerink, Francois Sigaux, Torsten Haferlach, Iwona Wlodarska, Peter Vandenberghe, Jean Soulier, Jan Cools
Journal: Blood (2009)
OPD-spectrum Disorders Clinical Collaborative Group. Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans
Authors: SP Robertson, Twigg, AJ Sutherland-Smith, Biancalana, RJ Gorlin, D Horn, SJ Kenwrick, Ca Kim, Eva Morava, R Newbury-Ecob, KH Orstavik, OW Quarrell, CE Schwartz, DJ Shears, M Suri, J Kendrick-Jones, AO Wilkie
Journal: Nature Genetics (2003)
Image Gallery: Segmental cutaneous leiomyomas in a patient with Reed syndrome
Authors: T. Russo, V. Piccolo, S. Staibano, R. Alfano, M. Mascolo, G. Argenziano
Journal: British Journal of Dermatology (2016)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, A 68‐year‐old woman was seen for painful segmental nodules of the left buttock (a, b). Medical history revealed a hysterectomy for uterine leiomyomatosis. Familial history was negative. Dermoscopic examination showed a light brownish network (c). Histology (d) was consistent with cutaneous leiomyoma. Because of the cutaneous–uterine leiomyomatosis (CUL), a diagnosis of Reed syndrome was made. Reed syndrome is an autosomal dominant disorder provoked by defects in the fumarate hydratase gene.1 A small proportion of patients affected by CUL will develop a renal cell carcinoma,2 therefore we have planned periodic ultrasound studies for our patient to monitor for any kidney tumours that might present.
Glomerular and Tubular Kidney Involvement in HCV Child-A Cirrhosis
Authors: D. Palazzo, E. Biliotti, F. Tinti, A. Bachetoni, P. Perinelli, A. Cappoli, M.D. D’Alessandro, S. Grieco, R. Labriola, M. Subic, I. Umbro, P. Rucci, A.P. Mitterhofer, G. Taliani
Journal: Journal of Hepatology (2016)
PD1.05 (also presented as P1.49): The Genomics of Young Emergent Lung Cancer
Authors: Barbara Gitlitz, Bonnie Addario, Alicia Sable-Hunt, Silvia Novello, Tiziana Vavala, Ruthia Chen, Marisa Bittoni, S. Lani Park, Mark Jennings, Geoffrey Oxnard
Journal: Journal of Thoracic Oncology (2016)
Angiopoietin-Like4 is Associated with Lipid Metabolism and Severe Fibrosis in Non-Diabetic Patients with Non-Alcoholic Fatty Liver Disease
Authors: C. Rosso, M. Gaggini, C. Saponaro, M. Marietti, G.P. Caviglia, F. Carli, E. Buzzigoli, M.L. Abate, A. Smedile, G.M. Saracco, A. Gastaldelli, E. Bugianesi
Journal: Journal of Hepatology (2016)
Correlation of immune responses with survival in a randomized phase II study investigating multipeptide vaccination with IMA901 plus or minus low-dose cyclophosphamide in advanced renal cell carcinoma (RCC).
Authors: H. Singh, N. Hilf, R. Mendrzyk, D. Maurer, T. Weinschenk, A. Kirner, J. Frisch, C. Reinhardt, A. Stenzl, S. Walter
Journal: Journal of Clinical Oncology (2010)

2587 Background: IMA901 is a therapeutic cancer vaccine based on the selection of naturally presented tumor-associated peptides (9 HLA class I- and 1 HLA class II-binding peptides). A previous phase I study showed a significant correlation of disease control rates (DCR) at 3 months with T-cell responses to multiple IMA901 peptides but not to a vaccinated control peptide. Methods: 68 HLA-A*02-positive metastatic clear-cell RCC patients progressing during or after first-line cytokine or TKI therapy were randomized 1:1 to receive repeated intradermal vaccinations of IMA901 together with 75 μ g GM-CSF plus/minus a single infusion of low-dose cyclophosphamide (CY; 300mg/m2) 3 days before the first vaccination. Clinical endpoints included DCR and overall survival (OS). Immunological endpoints included peripheral blood analysis of vaccine-induced peptide-specific T-cell responses to IMA901 (multimer and ELISpot analysis), FoxP3-positive regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and serum biomarkers. Results: The full clinical data is described in a separate abstract (Reinhardt et al.) with encouraging OS rates specifically in the CY-pretreated patients. Patients receiving CY showed a significant decrease of median Treg levels 3 days after CY treatment (p=0.032) and multipeptide responders in this group had significantly better OS than others (p=0.019). Additional data on MDSCs and further biomarkers will be presented at the meeting. Conclusions: This phase II study confirms that (1) vaccine-induced immune responses to IMA901 correlate with clinical benefit and (2) pretreatment with a single dose of cyclophosphamide down-modulates Tregs and contributes positively to OS. OS rates of immune-evaluable patients 6 months 12 months 18 months All patients (n=64) 77% 69% 55% Thereof non-multipeptide responders (n=47) 72% 63% 43% Thereof multipeptide responders (n=17) 88% 82% 82% All patients pretreated with low-dose CY (n=31) 84% 73% 63% Thereof non-multipeptide responders (n=23) 78% 61% 46% Thereof multipeptide responders (n=8) 100% 100% 100% Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration immatics biotechnologies GmbH immatics biotechnologies GmbH immatics biotechnologies GmbH
Clinical outcome and benefit of oxaliplatin in colon cancer according to intrinsic subtypes: Results from NRG Oncology/NSABP C-07.
Authors: Kay L. Pogue-Geile, Nan Song, Patrick G. Gavin, Greg Yothers, S. Rim Kim, Nicole L. Johnson, Corey Lipchik, Carmen Joseph Allegra, Nicholas J. Petrelli, Michael J. O'Connell, Norman Wolmark, Soonmyung Paik
Journal: Journal of Clinical Oncology (2016)

3510 Background: In the C-07 trial for stage II/III colon cancer, oxaliplatin added to 5-fluorouracil + leucovorin (FULV) provided significant but modest absolute benefit for DFS. We hypothesized that molecular subtypes would be associated with differential prognosis and benefit from oxaliplatin. Methods: C-07 cases were divided into discovery (n = 848) and validation (n = 881) cohorts based on the chronological order of tissue block submission. Patients (pts) from a discovery cohort were subtyped with the CRCA classifier described by Sadanandam et al (enterocyte, goblet-like, transit amplifying, stem-like, and inflammatory). A re-estimated centroid using 72 genes included in a custom nCounter gene code set was used to determine subtypes and their association with oxaliplatin benefit in the discovery cohort. The validation cohort was then prospectively examined with a prespecified statistical analysis plan. Post-hoc analysis included examination of the entire cohort with CRCA, CCS and CMS subtyping methods. Results: In both discovery and validation cohorts, stem-like subtype was associated with poor prognosis and lack of benefit from oxaliplatin. While stage III C-07 pts with an enterocyte subtype had a statistically significant benefit from oxaliplatin in the discovery cohort (Hazard Ratio [HR] = 0.223), only a trend for benefit was observed in the validation cohort (HR = 0.525, P= 0.141). Failure to validate may have been due to limited power or a limited number of genes defining the enterocytye subtype because the code set was designed before subtypes were described. Examination of the different subtyping methods shows that all 3 methods robustly identified the same poor prognostic pts (stem-like, CCS-3 and CMS-4). Conclusions: The apparent clinical utility of subtyping includes the identification of the stem-like subtype because it can be robustly identified, and have a very poor prognosis. Patients with stem-like subtype in our retrospective study received no benefit from oxaliplatin. Future clinical trials are required to determine the extent of the clinical utility of subtyping for oxaliplatin benefit. Support: U10-CA-180868, -189867, -180822; Sanofi Clinical trial information: NCT00004931.
Molecular Pathways: Targeting Steroid Receptor Coactivators in Cancer
Authors: David M. Lonard, Bert W. O'Malley
Journal: Clinical Cancer Research (2016)

Abstract Coactivators represent a large class of proteins that partner with nuclear receptors and other transcription factors to regulate gene expression. Given their pleiotropic roles in the control of transcription, coactivators have been implicated in a broad range of human disease states, including cancer. This is best typified by the three members of the steroid receptor coactivator (SRC) family, each of which integrates steroid hormone signaling and growth factor pathways to drive oncogenic gene expression programs in breast, endometrial, ovarian, prostate, and other cancers. Because of this, coactivators represent emerging targets for cancer therapeutics, and efforts are now being made to develop SRC-targeting agents, such as the SI-2 inhibitor and the novel SRC stimulator, MCB-613, that are able to block cancer growth in cell culture and animal model systems. Here, we will discuss the mechanisms through which coactivators drive cancer progression and how targeting coactivators represent a novel conceptual approach to combat tumor growth that is distinct from the use of other targeted therapeutic agents. We also will describe efforts to develop next-generation SRC inhibitors and stimulators that can be taken into the clinic for the treatment of recurrent, drug-resistant cancers. Clin Cancer Res; 22(22); 5403–7. ©2016 AACR.
Cancer survivorship care in the rural community: A mobile model.
Authors: Keith Edward Argenbright, Emily Berry, Tracy Mazour, Stephanie L. Lawrence
Journal: Journal of Clinical Oncology (2016)

38 Background: As survival rates continue to improve, many forms of cancer are now regarded as chronic diseases requiring long-term follow-up. This survivorship phase of care represents a distinct opportunity to improve the health and quality of life for cancer survivors, addressing the lingering medical and psychosocial effects of illness, recurrent or new cancers, and promoting health behavior changes. Evidence-based cancer survivorship programs are typically limited in scope and only found in large cancer centers because they are costly and poorly reimbursed. As a result, UT Southwestern Moncrief Cancer Institute (UTSW-MCI) mobilized its clinic to provide essential survivorship services to the estimated 15,000 underserved cancer survivors in geographically remote areas of North Texas. Methods: UTSW-MCI provides survivorship care to Medicaid-enrolled and uninsured patients within a nine county service area using a custom-built mobile health unit. Staffed with an experienced team of nurses, social workers, dietitians, exercise specialists and physician assistant, services on the mobile clinic include: cancer screening and surveillance; medical management of long-term side effects of treatment; treatment summary and care plans; dietary evaluations and healthy lifestyle education; psychosocial evaluations, care coordination and navigation to financial assistance; and assessments for balance, immobility, range of motion, and safe physical activity. In-house providers with the ambulatory clinic are also able to see patients on the mobile unit using telemedicine. These services include genetic counseling, physician assistant evaluations, and psychological counseling. Results: After six months, mobile clinic enrollments represent more than 10% (N = 28) of the survivorship program patient population and nearly 15% (N = 130) of completed encounters, including 28 RN assessments, 26 Social Work evaluations, 21 Dietitian assessments, 53 Exercise sessions, and 3 PA consultations. Conclusions: This innovative survivorship care model addresses barriers that impede access to care to improve both the health of medically underserved cancer survivors and the experience of care while reducing the cost of care without compromising quality.
Building pancreatic organoids to aid drug development
Authors: Edgar S Wills, Joost P H Drenth
Journal: Gut (2016)

Comment on: gutjnl-2016-312423 ‘Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling’

Much of our understanding of human diseases comes from the study of model systems such as cell lines. Cell lines are derived from cells that have obtained the property to proliferate indefinitely, often by immortalisation or isolation from cancerous tissues. They have the great advantage that they are easy to work with and can be kept in culture almost endlessly. The disadvantage is that they have lost the genetic signature of healthy primary cells, thwarting the interpretation of test results. This has led to the search for human cell systems that accurately recapitulate healthy or diseased human primary tissues. Advances in stem cell technology have made it possible to create, maintain and expand induced or adult stem cells while they retain multilineage potential. This has led to the development of the so-called organoids, which are defined as a three-dimensional (3D) cellular cluster derived exclusively from primary tissue, embryonic stem cells or induced pluripotent stem cells (iPSCs). Organoids are capable of self-renewal and self-organisation into multiple types of differentiated cells, while maintaining the phenotype of the original tissue. In view of these advantageous properties, organoids have been generated for many of the GI tissues, particularly colon and liver, and also stomach.1 ,2 Pancreatic organoids (POs) have gone through a long developmental phase and have recently matured to their first practical application. Starting with the discovery that …
P0607 : Prevention of vertical transmission of Hepatitis B: An evaluation of adherence rates and risk factors for failure to provide immunoprophylaxis therapy in a single Australian centre
Authors: L. Sahhar, S. Spring, P. Ha, N. Tan, V. Bull, W. Birkett, E. Lickliter, J. Lewis, T. Trivedi, S. Le, A. Dev
Journal: Journal of Hepatology (2015)
Patterns of Estimated Glomerular Filtration Rate Decline Leading to End-Stage Renal Disease in Type 1 Diabetes
Authors: Jan Skupien, James H. Warram, Adam M. Smiles, Robert C. Stanton, Andrzej S. Krolewski
Journal: Diabetes Care (2016)

OBJECTIVE The patterns of estimated glomerular filtration rate (eGFR) decline to end-stage renal disease (ESRD) in patients with type 1 diabetes has not been conclusively described. Decline could be linearly progressive to ESRD but with a variable rate. Conversely, decline may be linear but interrupted by periods of plateaus or improvements. RESEARCH DESIGN AND METHODS This observational study included 364 patients with type 1 diabetes attending the Joslin Clinic who developed ESRD between 1991 and 2013. We retrieved serum creatinine measurements from clinic visits or research examinations up to 24 years (median 6.7 years) preceding the onset of ESRD. Using serial measurements of serum creatinine to estimate renal function (eGFR), we used regression-based spline methods and a data smoothing approach to characterize individual trajectories of eGFR over time for the 257 patients with five or more data points. RESULTS The rate of eGFR decline per year ranged widely, from −72 to −2 mL/min/1.73 m2 (median −8.5). The trajectories, as characterized with linear regression-based spline models, were linear or nearly so for 87% of patients, accelerating for 6%, and decelerating for 7%. Smoothed trajectories evaluated by a Bayesian approach did not significantly depart from a linear fit in 76%. CONCLUSIONS The decline of eGFR in type 1 diabetes is predominantly linear. Deviations from linearity are small, with little effect on the expected time of ESRD. A single disease process most likely underlies renal decline from its initiation and continues with the same intensity to ESRD. Linearity of renal decline suggests using slope reduction as the measure of effectiveness of interventions to postpone ESRD.
Primary Care Sequential Use of FIB-4 and the Enhanced Liver Fibrosis Test to Stratify Patients with Non-alcoholic Fatty Liver Acide Doubles Cirrhosis Detection and Reduces Referrals of Patients with Mild Disease
Authors: A. Srivastava, R. Gailer, S. Demma, A. Warner, D. Suri, S. Morgan, S. Tanwar, K. Sennett, D. Thorburn, J. Parkes, E. Tsochatzis, W. Rosenberg
Journal: Journal of Hepatology (2016)
B Cell With Regulatory Function Are Enriched Within Transitional and IgM Memory B Cell Subsets In Healthy Donors But Are Reduced and Functionally Impaired In Patients With Chronic Graft-Versus-Host Disease
Authors: Anushruti Sarvaria, Ahmad Khoder, Abdullah Alsuliman, Claude Chew, Takuya Sekine, Nichola Cooper, Hugues de Lavallade, Muharrem Muftuoglu, Eric Yvon, Amir Hamdi, Amin Alousi, Lisa S St. John, David Marin, Kate Stringaris, Enli Liu, Jeffrey J. Molldrem, Nina Shah, Simrit Parmar, Ian K. McNiece, Richard E Champlin, Elizabeth J Shpall, Katayoun Rezvani
Journal: Blood (2013)
Impact of intermittent and maintenance chemotherapy on outcomes in metastatic colorectal cancer.
Authors: Jonathan M. Loree, Sean K.R. Tan, Laurence Lafond, Hagen F. Kennecke, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2016)

6566 Background: With improved survival, clinicians managing metastatic colorectal cancer (mCRC) increasingly consider intermittent chemotherapy (IC) where patients receive a complete treatment break (TB) or maintenance chemotherapy (MC) where parts of a combination regimen are omitted. These modifications can improve quality of life (QoL) but their impact on outcomes is poorly understood. Methods: Using a population-based cohort of mCRC patients (pts) diagnosed from 2008 to 2010, we aimed to describe use of IC and MC and to compare median overall survival (mOS) in pts with and without these treatment modifications. IC was defined as TB intervals of ≥ 45 days without any cytotoxic agents while MC was defined as omission of one cytotoxic agent for ≥ 1 cycle. We examined outcomes using Kaplan-Meier methods, Cox regression, and propensity-score adjusted analyses. Results: Among 1249 mCRC pts, 279 (22%) underwent IC and had ≥ 1 TB, with median duration of 91 (IQR 63-158) days. TBs occurred at a median of 127 (IQR 57-234) days from initiation of a line of therapy and most pts (71%) only received 1 TB. In the 617 pts receiving a combination regimen, 120 (19%) had periods of MC, of which 68 (57%) had re-introduction of the omitted agent. On univariate analyses, patients undergoing IC (mOS 39 vs 23 months, P< 0.001) or MC (mOS 36 months vs 24 months, P= 0.0015) demonstrated better OS. In patients on MC, OS improvement was noted when the agent was restarted (mOS 41 months vs 24 months, P= 0.0073), but not without resumption (mOS 36 vs 24 months, P= 0.051). Using propensity scores and stratifying by treatment regimen, IC was not associated with altered OS (P > 0.05 across all regimens). In multivariate analysis adjusting for age, gender and regimen, MC was correlated with improved OS (HR 0.71, 95% CI 0.58-0.88, P= 0.002). When considering whether an omitted agent was re-introduced, MC with re-escalation (HR 0.68 95% CI 0.49-0.96, P= 0.027) was associated with improved OS, but not MC without re-escalation (HR 0.67 95% CI 0.50-0.91, P= 0.10). Conclusions: In patients with mCRC, IC and MC are reasonable options to maintain QoL and do not appear to negatively impact OS in carefully selected patients.