tbuckley/cabot-search huggingface dataset:
Impact of comorbidities on outcomes of elderly patients with diffuse large B‐cell lymphoma
Authors: Caner Saygin, Xuefei Jia, Brian Hill, Robert Dean, Brad Pohlman, Mitchell R. Smith, Deepa Jagadeesh
Journal: American Journal of Hematology (2017)

International prognostic index (IPI) has remained the primary prognostic tool in diffuse large B cell lymphoma (DLBCL) for more than 20 years. Even though the disease is more common in older population, the impact of comorbidities, dose reductions, and treatment-related adverse events (TAEs) on the outcome in elderly DLBCL patients has not been well established. We studied 413 consecutive patients aged ≥ 60 years who were treated at the Cleveland Clinic. The median age at diagnosis was 69 years, 58% of patients had high IPI score, and 85% had low Charlson comorbidity index (CCI). Forty percent of patients required dose reductions during treatment, 78% achieved CR, and 70% experienced at least one grade II-IV TAE. High IPI score, high CCI, reduced dose chemotherapy, TAE, and hospitalization were significant predictors of death and relapse. In multivariable analysis, high IPI and CCI were independent predictors of overall and progression free survival. A simple model combining IPI and CCI could reliably distinguish three prognostically separate risk groups. Our results suggest that incorporation of CCI in current prognostic models can improve prognostication of older DLBCL patients and CCI might be a valuable tool in evaluating the eligibility of older patients for clinical trial enrollment.
Abstract 390: End-stage Human Heart Failure is Characterized by a Deficit in Energetic Lipids in Both Diabetic and Non-diabetic Patients
Authors: Kenneth C Bedi, Nathaniel W Snyder, Ali Javaheri, Jeffery Brandimarto, Clementina Mesaaros, Ian A Blair, Kenneth B Margulies, J. E Rame
Journal: Circulation Research (2015)

Introduction: Animal models and human studies have identified increased intramyocardial lipid accumulation and a lipotoxicity hypothesis has been emerging as a mechanism of myocardial dysfunction in diabetes. We have identified a significant decrease in energetic lipids in chronic advanced non-diabetic heart failure. We hypothesized that intramyocardial lipid species would be increased in diabetic as compared to non-diabetic end-stage heart failure patients. Methods: Left ventricular samples procured at the time of orthotopic heart transplantation from non-diabetic (IDCM n=8) and diabetic (DCMDM n=8) patients as well as organ donors with (NFDM) and without a history of diabetes (Donor) were quantitated for lipids with high-resolution mass spectrometry . Stable isotope labeled essential nutrient in cell culture internal standards for acyl-CoAs were generated using [ 13 C 3 15 N 1 ]-pantotheonate in Hepa1c1c7 cells. Results: The lipidomic signature of end-stage failing myocardium marked by a significant decrease in energetic lipids, a decreased myocardial Succinyl CoA (p-value 0.0079 for failing versus non-failing diabetic subjects) and a decreased ratio of [Succinyl CoA]/[Acetyl Coa] consistent with deficient TCA cycling, is indistinguishable in diabetic and non-diabetic patients (Figure 1). Discussion: Despite the known bioenergetic deficits in insulin-resistant diabetes, we have not identified any significant differences between diabetic and non-diabetic subjects in the lipidomic signature of end-stae failing myocardium. Future studies are needed with focused metabolomics to elucidate differences in the diabetic phenotype of human heart failure.
Feasability of contrast-enhanced CT in breast conservation surgery for invasive and non-invasive breast cancer.
Authors: Yoshihiko Kamada, Kentaro Tamaki, Kanou Uehara, Nobumitsu Tamaki
Journal: Journal of Clinical Oncology (2017)

e12084 Background: MRI imaging has become the standard for planning breast conservation surgery for breast cancer. However, due partly to lack of resources of a small clinic practice, we have been utilizing contrast enhanced CT facilitated with ultrasound for this purpose. The aim of this presentation is to assess the feasability of contrast-enhanced CT in breast conservation surgery. Methods: We used GE Brightspeed-8 CT, with HP Z440 workstation (for free line masking). 100 mld of Iopamidol contrast medium was injected at a rate of 3 ml/sec and image capture was done at the 60 or 180 second phase. Images were taken with the patient in a supine position. We evaluate a total of 2057 cases operated in a ten year period between 2005.1.1 to 2014.12.31, excluding cases receiving preoperative chemotherapy. 1,757 cases (85%) were invasive and 300 cases (15%) were non-invasive breast cancer cases. Results: Lesion localization by contrast-enhance CT was acceptable by predefined criteria in 72% of invasive carcinoma cases, and 89% non-invasive carcinoma cases. The breast conservation rate was 77% and 83% for invasive and non-invasive breast cancer cases, respectively. Surgical margins were positive “on ink” for 8 cases (0.6%), and positive within 5 mm (including DCIS) in 340 cases (25.1%) of the 1,357 invasive cancer cases treated with BCT. There were 7 completion total mastectomies and 3 partial mastectomies for the patients with positive margins (11/340 = 3.2%). Surgical margins were positive for 78 cases (31.3%) of the 249 DCIS cases undergoing BCT. There was 1 completion mastectomy and 2 partial mastectomies for the patients with positive margins (3/78 = 3.8%). Local recurrence rates for invasive and non-invasive breast cancer cases undergoing BCT were 2.6% (average observation period 65.0 months) and 2.8% (average observation period 64.4 months), respectively. Conclusions: Contrast-enhanced CT facilitated with ultrasound imaging is an effective and easy to implement modality for planning breast conservation surgery in invasive and non-invasive breast cancer, possibly in part due to imaging that corresponds closely to the breast position during surgery.
Ultradeep-Amplicon Pyrosequencing for Mutation Detection in the Kinase Domain of BCR-ABL Revealed Artificial Low-Level Variants That Need to Be Avoided for Relevant Mutational Data Interpretation
Authors: Adela Brouckova, Simona Soverini, Caterina De Benedittis, Hana Klamova, Cyril Salek, Marek Trneny, Michele Baccarani, Giovanni Martinelli, Katerina Machova Polakova
Journal: Blood (2012)
Méta analyse de la performance des coloscopes ultra-fins versus coloscopes standards
Journal: Endoscopy (2017)

Une coloscopie se doit d’atteindre le caecum sans inconfort ni complication. L’intubation caecale est obtenue dans plus de 95 % des cas avec un coloscope standard. Les facteurs d’échec sont l’âge avancé, le sexe féminin, des angles aigus, des segments coliques fixés par des antécédents de diverticule ou de chirurgie abdominale. Dans ces conditions, le risque de douleur et de perforation augmente. Si la coloscopie est incomplète, d’autres examens seront nécessaires (lavement baryté ou un coloscanner) avec le problème des faux positifs et d’une nouvelle coloscopie dans d’autres conditions : anesthésie générale (AG), coloscope à rigidité variable, coloscopie avec un gastroscope. Les coloscopes ultra fins semblent intéressants mais aucune étude n’a pu montrer leur supériorité par rapports aux appareils standards. D’où l’intérêt de cette méta-analyse.
Erratum: Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease (Annals of Internal Medicine (2001) 135 (73-87))
Authors: T. H. Jafar, C. H. Schmid, M. Landa, I. Giatras, R. Toto, G. Remuzzi
Journal: Annals of Internal Medicine (2002)
Unprecedented Prevalence of Laryngopharyngeal Reflux (LPR) Amongst Gastro-Oesophageal Reflux (GORD) Sufferers. Is Underdiagnosis Leading to Mismanagement of GORD Patients?
Authors: C Power, PJ Byrne, P Lawlor, T Moran, N Ravi, PWN Keeling, JV Reynolds
Journal: Endoscopy (2004)

Introduction: Laryngopharyngeal Reflux (LPR) exists if there are >3 episodes of pharyngeal pH <5 in a 24 hr period. The larynx is exquisitely sensitive to peptic injury and LPR has been implicated in the aetiology of many conditions including laryngeal carcinoma. LPR has been considered an otolaryngological (ENT) condition as fewer than 10% of patients manifest oesophagitis or Barretts oesophagus. We undertook to assess the prevalence of LPR in a cross-section of ENT and gastro-oesophageal reflux (GORD) patients.
NICE approves trastuzumab emtansine after deal with drug company
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

A new deal on the advanced breast cancer drug trastuzumab emtansine (marketed by Roche as Kadcyla) means that it can now be recommended for routine use on the NHS, the National Institute for Health and Care Excellence (NICE) has said.1

The latest draft guidance on trastuzumab emtansine reverses a previous recommendation issued last December in which NICE said that the drug was too expensive.2 The cost of £90 000 (€103 000; $115 000) for an average course of treatment (14.5 months) gives trastuzumab a cost per quality adjusted life year (QALY) of £166 000, which was well above the normal threshold for drugs used …
Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor
Authors: Zhaoming Wang, Katherine A McGlynn, Ewa Rajpert-De Meyts, D Timothy Bishop, Charles C Chung, Marlene D Dalgaard, Mark H Greene, Ramneek Gupta, Tom Grotmol, Trine B Haugen, Robert Karlsson, Kevin Litchfield, Nandita Mitra, Kasper Nielsen, Louise C Pyle, Stephen M Schwartz, Vésteinn Thorsson, Saran Vardhanabhuti, Fredrik Wiklund, Clare Turnbull, Stephen J Chanock, Peter A Kanetsky, Katherine L Nathanson
Journal: Nature Genetics (2017)
Duration of Therapy Is Independently Associated with Improved Progression Free and Overall Survival Following First Line Therapy for Non-Transplant Eligible Patients with Multiple Myeloma: Retrospective Analysis from a Single Centre
Authors: Dunnya De-Silva, Adam Bloomfield, Nicholas Counsell, Simon Cheesman, Ali Rismani, Neil Rabin, Shirley D'Sa, Charalampia Kyriakou, Jayne Galinsky, Sarah Richard, Rakesh Popat, Atul Mehta, Kwee L Yong
Journal: Blood (2016)
Abstract 238: Role of Erythropoietin Signaling in the Biology of Mouse Cardiac Progenitor Cells
Authors: Maria P Zafiriou, Claudia Noack, Michael Didie, Bernhard Unsoeld, Ali El-Armouche, Martin W Bergmann, Wolfram H Zimmermann, Laura C Zelarayan
Journal: Circulation Research (2012)

Erythropoietin (Epo) was shown to improve cardiac function following ischemia reperfusion mainly via neo-angiogenesis and anti-apoptotic mechanisms. We found EpoR expression to be particularly high in adult cardiac progenitor cells (CPCs). Thus, we reasoned that Epo may play a role in the biology of these cells. We isolated CPCs from adult C57BL/6 hearts by enzymatic digestion and filtration (pore size: 30 µm). By means of immunofluorescence microscopy (IF) and flow cytometry (FC) we analyzed EpoR expression in the CPCs. 24±3% of the investigated cardiac cells were positive for EpoR with 3±2% of these being c-kit+ and 28%±2% Sca-1+. 52% of the EpoR+ cells expressed endothelial cell markers (40±2% CD34+, 9±2% FLK1+). 42±4% expressed myocyte markers (αMHC+, cTNT+). IF revealed a progenitor-like population with immature cell morphology and proliferation potential (ki67+). Cell cycle analysis showed an enrichment of αMHC+ EpoR+ cells in S and G2 phase (49±7%, n=3) as compared to the αMHC- EpoR- population (13±3%, n=3). Moreover, we tested the effect of Epo in the biology of these CPCs in vitro. At d14 we observed a two-fold increase of GATA4+ and cTnT+ cardiac cells in the co-cultures treated with Epo (n=3). CPC cycle arrest abrogated the aforementioned effects, suggesting that Epo influences mainly CPC proliferation. Finally, we tested the potential of Epo to protect against ischemia by inducing the proliferation of these αMHC+ CPCs in vivo in a myocardial infarction (MI) model. 4 weeks post MI, echocardiography did not reveal a significant functional improvement of the Epo receiving mice (2x, 2U/g Epo i.p). Nevertheless, FC analysis of the progenitor pool showed a significant augmentation of αMHC+ and cTnT+ cells (Sham: 19±3% vs Epo 35±3%, n=5; MI: 10.6±2.3%, n=6 vs Epo 20.3±1.9%, n=8). These data suggest an activation of myogenic progenitors by Epo, despite the lack of apparent regeneration under the investigated conditions. In conclusion, we found that EpoR is expressed in a putative cardiomyogenic progenitor cell pool in the adult heart. Epo drives their proliferation in vitro and in vivo even upon acute cardiac injury. We are currently investigating the long-term consequences of the observed progenitor cell activation in models of chronic ischemic injury.
Colon Pathology Characteristics in Li–Fraumeni Syndrome
Authors: William Rengifo-Cam, Hailey M. Shepherd, Kory W. Jasperson, N. Jewel Samadder, Wade Samowitz, Sheryl R. Tripp, Joshua D. Schiffman, Wendy Kohlmann
Journal: Clinical Gastroenterology and Hepatology (2017)
Foxp3+ regulatory T Cells Maintain Bone Marrow Microenvironment for B Cell Differentiation from Hematopoietic Stem Cells
Authors: Hidekazu Nishikii, Antonio Pierini, Yasuhisa Yokoyama, Takaharu Kimura, Hye-Sook Kwon, Maite Alvarez, Jeanette Baker, Judith Shizuru, Joy Wu, Shigeru Chiba, Robert S. Negrin
Journal: Blood (2016)
Juvenile myelomonocytic leukemia in an infant with congenital human immunodeficiency virus and cytomegalovirus infection
Authors: Jessica Bazin, Leena Karnik, Gareth Tudor‐Williams, Anne M. Kelly, Barbara J. Bain
Journal: American Journal of Hematology (2017)

An 11-month-old boy was found to have bicytopenia and leukocytosis on routine attendance at a pediatric infectious diseases clinic. The child was under review for congenital co-infection with the human immunodeficiency virus (HIV) and cytomegalovirus (CMV). He was on antiretroviral therapy and had previously been treated with valganciclovir. His foster mother had no new concerns, and he had not had any fever recently. No significant abnormality was found on physical examination. His blood count showed a normocytic normochromic anemia (hemoglobin concentration 95 g/L), white cell count 26.5 × 109/L, and platelet count 47 × 109/L. There was monocytosis (7.7 × 109/L) and basophilia (0.3 × 109/L). In addition his blood film showed nucleated red blood cells, dysplastic basophils and eosinophils, granulocyte precursors, and occasional blast cells (images). High performance liquid chromatography showed hemoglobin F of 37%. Opinion was divided as to whether the abnormalities were secondary to CMV infection or malignancy. A diagnosis of juvenile myelomonocytic leukemia (JMML) was favored and further investigations were therefore performed. Abdominal ultrasound examination showed the spleen to measure 9.5 cm. A bone marrow aspirate showed active erythropoiesis with reduced granulopoiesis and megakaryocytes. Blast cells were 7% on cytology and 10% on flow cytometry; they expressed CD45 (moderate), CD33, CD117, CD7, and CD56. Monocytic markers were expressed by 32% of cells: CD45 (strong), CD4 (weak), CD64, CD11b, CD13, CD14, CD36, and CD56. Fluorescence in situ hybridization showed monosomy 7 in 64% of cells. Molecular analysis showed an NRAS Q61K mutation (PTPN11 and KRAS were wild type). Subsequently he was found to have a negative PCR for CMV, a low HIV viral load and a CD4-positive lymphocyte count of 2770 × 106/L. CMV infection in infants can cause a leukemoid reaction that resembles JMML.1 However an increased basophil count, dysplastic eosinophils and basophils, and an increased hemoglobin F would not be expected. Careful examination of the blood film suggested the correct diagnosis, which was confirmed by bone marrow examination and cytogenetic analysis. None.
A retrospective analysis of the ICOGEN clinical trial demonstrates the utility of VeriStrat to predict outcome in an all Chinese cohort treated with EGFR TKI.
Authors: Yuankai Shi, Xiaohong Han, Li Zhang, Lieming Ding, Nicholas Dupuis, Alex Nickel, Lana Feng, Gary Anthony Pestano, Xiaoqing Liu, Caicun Zhou, Li Zhang, Shucai Zhang, Dong Wang, Qiang Li, Shukui Qin, Chunhong Hu, Yiping Zhang, Jianhua Chen, Fenlai Tan, Yan Sun
Journal: Journal of Clinical Oncology (2016)

e20626 Background: VeriStrat, a blood-based MALDI-TOF mass spectrometry serum protein test has been shown to have both prognostic and predictive utility for EGFR targeted therapies in NSCLC.1In an analysis of an all Chinese patient population, VeriStrat was used to classify subjects from the ICOGEN2 clinical trial which compared icotinib,an EGFR-TKI available in China, with gefitinib on NSCLC patients who have had one or two prior chemotherapies. Methods: Pre-treatment plasma samples from the ICOGEN clinical trial were analyzed with VeriStrat which classified subjects with respect to predefined reference groups VS-G and VS-P. Clinical outcomes were analyzed as a function of both treatment arm and VeriStrat status. Results: From the ICOGEN trial, 357 subjects were classified (VS-G: 283; VS-P: 74) with VeriStrat. In the cumulative patient population stratified by VeriStrat but inclusive of both treatmentarms the median OS was 16.5 mo. and 5.75 mo. (HR [95% CI] 0.47 [0.25 – 0.49]; p < 0.001) and median PFS was 5.25 mo. and 2.5 mo. (HR [95% CI] 0.62 [0.40 – 0.73]; p < 0.001) in the VS-G and VS-P groups respectively.Results were similar within the icotinib arm where the median OS was 16.5 mo. and 4.25 mo. (HR [95% CI] 0.35 [0.11–0.39]; p < 0.001) and median PFS was 7.0 mo. and 2.0 mo. (HR [95% CI] 0.46 [0.19 – 0.48]; p < 0.001) in the VS-G and VS-P groups respectively. Conclusions: The blood-based test VeriStrat provides a rapid method for determining the likely response of patients to an EGFR TKI therapy in the second line. Specifically, in this all Chinese cohort, patients classified as VS-G performed significantly better in PFS and OS than those classified VS-P.
RNA-containing exosomes in induced sputum of asthmatic patients
Authors: Sara Sánchez-Vidaurre, Maria Eldh, Pia Larssen, Kameran Daham, Maria-Jose Martinez-Bravo, Sven-Erik Dahlén, Barbro Dahlén, Marianne van Hage, Susanne Gabrielsson
Journal: Journal of Allergy and Clinical Immunology (2017)
The need for a complex systems model of evidence for public health
Authors: Harry Rutter, Natalie Savona, Ketevan Glonti, Jo Bibby, Steven Cummins, Diane T Finegood, Felix Greaves, Laura Harper, Penelope Hawe, Laurence Moore, Mark Petticrew, Eva Rehfuess, Alan Shiell, James Thomas, Martin White
Journal: The Lancet (2017)
High hepatitis C cure rates among black and nonblack human immunodeficiency virus–infected adults in an urban center
Authors: Oluwaseun Falade‐Nwulia, Catherine Sutcliffe, Juhi Moon, Geetanjali Chander, Tanyaporn Wansom, Jeanne Keruly, Jennifer Katzianer, Amy Nathanson, Jillian Marks, Shruti Mehta, David Thomas, Richard Moore, Mark Sulkowski
Journal: Hepatology (2017)

Hepatitis C virus (HCV) cure rates have been similar in patients with and without human immunodeficiency virus (HIV) coinfection; however, in the ION‐4 study, black patients treated with ledipasvir/sofosbuvir (LDV/SOF) were significantly less likely to achieve cure (90%) compared to nonblack patients (99%). There are limited real‐world data on the effectiveness of oral direct‐acting antivirals (DAAs) in predominantly minority HIV/HCV coinfected populations. We analyzed HCV treatment outcomes among 255 HCV coinfected patients initiating DAAs between February 2014 and March 2016 in an urban clinic in Baltimore, Maryland. To facilitate adherence, patients received standardized HIV nurse/pharmacist support, which included nurse visits and telephone calls. Median age was 43 years, 88% were black, 73% male, 69% had a history of injection drug use, 45% a history of hazardous alcohol use, and 57% a comorbid psychiatric diagnosis. Median CD4 count was 577 (interquartile range, 397‐820) cells/mm 3 ; most (97%) were on antiretroviral therapy, had HIV RNA &lt;20 copies/mL (87%), and were infected with HCV genotype 1 (98%). Over 60% had significant fibrosis (Fibrosis‐4 Index score 1.45‐3.25 [44%] and &gt;3.25 [17%, cirrhosis]) and 30% were HCV treatment experienced. The majority of patients received LDV/SOF with or without ribavirin (91%) and were treated for 12 weeks. Overall, the sustained virological response rate was 97% (95% confidence interval [CI], 93‐98) and did not vary by race (black, 96% [95% CI, 93‐98]; nonblack, 97%, [95% CI, 83‐99]), history of injection drug use, alcohol use, or psychiatric diagnosis. Conclusion : HCV treatment was highly effective among HIV‐infected patients who received care within an integrated nurse/pharmacist adherence support program. These results suggest that race and psychosocial comorbidity may not be barriers to HCV elimination. (H epatology 2017;66:1402–1412).
The Hope and Hype of CRISPR-Cas9 Genome Editing
Authors: Kiran Musunuru
Journal: JAMA Cardiology (2017)

<h3>Importance</h3> Clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated protein 9 (CRISPR-Cas9) has garnered a great degree of attention since its first reported uses in mammalian cells in early 2013 due to its perceived impact with respect to potential research applications and, especially, therapeutic applications. <h3>Observations</h3> CRISPR-Cas9 is being widely used in the laboratory and has greatly improved the ability to generate genetically modified animal models of human diseases. First steps have been reported with respect to proof-of-concept cardiovascular therapeutic applications in mouse models—which might eventually lead to new treatments for patients—as well as modification of human embryos, which raises a host of social, ethical, and legal questions. <h3>Conclusions and Relevance</h3> CRISPR-Cas9 is already having a substantial effect on cardiovascular basic science research. Although the first steps toward potential therapies have been taken, there are substantial obstacles that will need to be overcome if CRISPR-Cas9 is to be used in the practice of cardiovascular medicine.