tbuckley/cabot-search huggingface dataset:
A Randomized, Phase II Study with Biomarker Analysis of Panobinostat with or without Rituximab in Relapsed Diffuse Large B Cell Lymphoma
Authors: Sarit Assouline, Michael Crump, Torsten Holm Nielsen, Miguel Alcaide, David Macdonald, Axel Tosikyan, Tina Haliotis, Celia Greenwood, Kathleen Klein Oros, Ryan Morin, Nathalie Johnson, Koren Kathleen Mann
Journal: Blood (2015)
Favorable Prognostic Impact of WT1 SNP rs16754 in Cytogenetically Normal AML Independent of MN1, BAALC, and ERG Expression.
Authors: Frederik Damm, Juergen Krauter, Iyas Hamwi, Michael A. Morgan, Gudrun Goehring, Brigitte Schlegelberger, Arnold Ganser, Michael Heuser
Journal: Blood (2009)
Azacitidine Plus Gemtuzumab Ozogamicin (GO): A Novel Combination in the Treatment of Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS) in the Elderly.
Authors: Sucha Nand, John Godwin, Scott Smith, Kevin Barton, Eliza Germano, Patrick Stiff
Journal: Blood (2006)
Treatment with Imatinib in Very Elderly (&amp;gt; 75 Years) CML Patients.
Authors: Roberto Latagli Ata, Massimo Breccia, Simona Sica, Antonio Spadea, Ada D’Addosio, Ida Carmosino, Silvia De Matteis, Caterina Stefanizzi, Paola Volpicelli, Laura Napoleone, Federico Vozella, Maria Concetta Petti, Giuliana Alimena
Journal: Blood (2008)
The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling
Authors: Rein M. G. J. Houben, Peter J. Dodd
Journal: PLoS Medicine (2016)

Background The existing estimate of the global burden of latent TB infection (LTBI) as “one-third” of the world population is nearly 20 y old. Given the importance of controlling LTBI as part of the End TB Strategy for eliminating TB by 2050, changes in demography and scientific understanding, and progress in TB control, it is important to re-assess the global burden of LTBI. Methods and Findings We constructed trends in annual risk in infection (ARI) for countries between 1934 and 2014 using a combination of direct estimates of ARI from LTBI surveys (131 surveys from 1950 to 2011) and indirect estimates of ARI calculated from World Health Organisation (WHO) estimates of smear positive TB prevalence from 1990 to 2014. Gaussian process regression was used to generate ARIs for country-years without data and to represent uncertainty. Estimated ARI time-series were applied to the demography in each country to calculate the number and proportions of individuals infected, recently infected (infected within 2 y), and recently infected with isoniazid (INH)-resistant strains. Resulting estimates were aggregated by WHO region. We estimated the contribution of existing infections to TB incidence in 2035 and 2050. In 2014, the global burden of LTBI was 23.0% (95% uncertainty interval [UI]: 20.4%–26.4%), amounting to approximately 1.7 billion people. WHO South-East Asia, Western-Pacific, and Africa regions had the highest prevalence and accounted for around 80% of those with LTBI. Prevalence of recent infection was 0.8% (95% UI: 0.7%–0.9%) of the global population, amounting to 55.5 (95% UI: 48.2–63.8) million individuals currently at high risk of TB disease, of which 10.9% (95% UI:10.2%–11.8%) was isoniazid-resistant. Current LTBI alone, assuming no additional infections from 2015 onwards, would be expected to generate TB incidences in the region of 16.5 per 100,000 per year in 2035 and 8.3 per 100,000 per year in 2050. Limitations included the quantity and methodological heterogeneity of direct ARI data, and limited evidence to inform on potential clearance of LTBI. Conclusions We estimate that approximately 1.7 billion individuals were latently infected with Mycobacterium tuberculosis (M.tb) globally in 2014, just under a quarter of the global population. Investment in new tools to improve diagnosis and treatment of those with LTBI at risk of progressing to disease is urgently needed to address this latent reservoir if the 2050 target of eliminating TB is to be reached.
Pulmonary Edema Occurring 15 Years After Mitral Valve Replacement
Authors: Amita Singh, Takeyashi Ota, Roberto M. Lang
Journal: JAMA Cardiology (2016)

A 77-year-old man with a history of mitral valve replacement , previous coronary artery bypass grafting, atrial fibrillation, and heart failure presented to our clinic for evaluation of worsening exertional dyspnea. What is your diagnosis?
Low Mutation Rate and No Significant Prognostic Implication of SF3B1, U2AF1 and SRSF2 Genes in Myelodysplastic Syndrome without Harboring Ring Sideroblast
Authors: Hye-Ran Kim, Trang Nguyen Thi Dai, Min-Gu Kang, Stephanie J. Won, Hwan-Young Kim, Jung-Yun Ko, Jong-Hee Shin, Soon-Pal Suh, Dong-Wook Ryang, Myung-Geun Shin
Journal: Blood (2012)
Use of a genome-wide linkage screen to identify a hereditary neuroblastoma predisposition locus at chromosome 2p24–23
Authors: Y. P. Mosse, L. Longo, M. Laudenslager, P. Perri, G. Tonini, C. M. McConville, F. Speleman, H. Hakonarson, E. Rappaport, M. Devoto, J. M. Maris
Journal: Journal of Clinical Oncology (2008)

10010 Background: A subset of neuroblastomas show inheritance as an autosomal dominant trait with incomplete penetrance. Familial neuroblastoma is often lethal during childhood, resulting in very few pedigrees of sufficient size for linkage analysis. Low-resolution genetic approaches have not been successful in identifying a narrow genomic region consistent with linkage, a critical first step in identifying the causal gene. Methods: We performed a genome-wide scan for linkage in eighteen neuroblastoma pedigrees at ∼6000 single nucleotide polymorphisms. Parametric and non-parametric analyses were used to identify and refine candidate regions. Candidate genes were resequenced in a panel of 15 probands using Sanger-based or 454 technology. Results: We discovered a highly significant linkage signal covering a 34 Mb region on chromosome 2p with a maximum non-parametric LOD score of 4.23 (p=0.00001), and 13/18 families screened were consistent with linkage to this locus. No other genomic region was suggestive of linkage in these families, including previously identified 4p16 and 16p12–13 loci. To further refine the 2p region, we performed parametric analyses in which we varied gene frequency and penetrance assumptions across a broad range. All analyses supported the initial inference of linkage, with a maximized LOD score of 6.37 (p=0.0000019) at rs1344063. By mapping informative recombination events, we defined a 16 Mb putative predisposition locus at 2p24–23, a region that includes the MYCN oncogene. Resequencing of an 18 Kb region surrounding the MYCN gene in probands from each linked family showed no activating mutations or novel sequence variations. Resequencing of other neurodevelopmental regulatory genes including NAG, DDX1, GDF7, and OSR1 has excluded these as neuroblastoma predisposition genes. Results of ongoing resequencing of a prioritized list of positional candidates will be reported. Conclusions: A hereditary neuroblastoma predisposition gene is located within a 16 Mb region at 2p24–23. We speculate that inactivation of this gene may also influence the development of non-familial human neuroblastomas. No significant financial relationships to disclose.
Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases
Authors: Sophia Frentzas, Eve Simoneau, Victoria L Bridgeman, Peter B Vermeulen, Shane Foo, Eleftherios Kostaras, Mark R Nathan, Andrew Wotherspoon, Zu-hua Gao, Yu Shi, Gert Van den Eynden, Frances Daley, Clare Peckitt, Xianming Tan, Ayat Salman, Anthoula Lazaris, Patrycja Gazinska, Tracy J Berg, Zak Eltahir, Laila Ritsma, Jacco van Rheenen, Alla Khashper, Gina Brown, Hanna Nyström, Malin Sund, Steven Van Laere, Evelyne Loyer, Luc Dirix, David Cunningham, Peter Metrakos, Andrew R Reynolds
Journal: Nature Medicine (2016)
Prognosis In Patients with MDS or AML and Bone Marrow Blasts Between 10% and 30% Is Not Associated with Blast Count but Depends on Cytogenetic and Molecular Genetic Parameters
Authors: Torsten Haferlach, Ulrike Bacher, Tamara Alpermann, Susanne Schnittger, Wolfgang Kern, Claudia Haferlach
Journal: Blood (2010)
Feasibility and safety of detection of sentinel node in lung cancer
Authors: R. Barcelo-Galindez, N. Uribe-Etxebarria, A. Viteri, J. Genollá, U. Jimenez-Maestre, M. Lorenzo-Martín, G. Rios, R. Rojo-Marcos, J. Rumbero-Sanchez, J. Pac-Ferrer
Journal: Journal of Clinical Oncology (2009)

7587 Background: Sentinel node (SN) can be detected in the drainage of many primary cancers and is considered a standard procedure in some tumors. For resectable lung cancer its study has began recently and its detection has not yet been standardized. Objective: To study the feasibility and safety of SN detection during surgery for lung cancer. Methods: Patients with non-small cell lung cancer, clinical stage I, amenable to surgery were eligible. Written informed consent was obtained in each patient before the procedure. Technique, as described by Liptay et al, consisted of four injections of albumin labelled with Technetium 99 , 0,25 mCi each peritumorally, and five minutes later, lobectomy and lymphadenectomy were associated with detection of SN (both in vivo and ex vivo). Results: From Jan 2006 to Nov 2008, the first 37 patients were included. In 35 patients one SN was detected, and in 2 there were two SN. SN was found in the lymphatic stations 10 or 11, except for tumors located in the left upper lobe, where two cases of a SN were found in station 5 and 6 each. In 23 cases of 37, both SN and lymphadenectomy were free of tumor. In seven of 37, SN was positive (in one, micrometastasis was detected with haematoxilin-eosin), and the rest of the nodes were free of tumor. In five of 37, SN and another node were positive. In two of 37, SN was falsely negative as one peribronchial node was positive but masked by radioactivity in the injected lung, one in right lower lobe and another in left lower lobe. Accuracy was 94,6%, sensibility 86%, specificity 100%, positive predictive value 100% and negative predictive value 92%. No relevant prolongation of surgery time was observed (5–15 minutes), and no morbidity or mortality related to this technique were seen. The cost of the materials used was 100 Euro per patient. Recruitment is ongoing. Conclusions: SN can be detected with a very high accuracy in lung cancer. This technique is feasible and safe, and does not add excessive cost or difficulty to the surgery of lung cancer. Modifications of the technique, using metabolic isotopes or new portatil 3D gamma detectors can be incorporated. Its final role in the staging and treatment of lung cancer is still unknown. Supported in part by a grant of the FIS (Fondo de Investigaciones Sanitarias), Spain. No significant financial relationships to disclose.
The Effect of Rituximab on Mobilization with AMD3100 Plus G-CSF in Patients with Relapsed or Refractory NHL or HD.
Authors: Jonathan L. Kaufman, Amanda M. Cook, Christopher Flowers, Amelia A. Langston, Sagar Lonial, Mary Jo Lechowicz, H. Jean Khoury, Gary Calandra, Ned Waller
Journal: Blood (2007)
Effects of high-intensity interval training on cardiometabolic health: a systematic review and meta-analysis of intervention studies
Authors: Romeo B Batacan, Mitch J Duncan, Vincent J Dalbo, Patrick S Tucker, Andrew S Fenning
Journal: British Journal of Sports Medicine (2016)

The current review clarifies the cardiometabolic health effects of high-intensity interval training (HIIT) in adults. A systematic search (PubMed) examining HIIT and cardiometabolic health markers was completed on 15 October 2015. Sixty-five intervention studies were included for review and the methodological quality of included studies was assessed using the Downs and Black score. Studies were classified by intervention duration and body mass index classification. Outcomes with at least 5 effect sizes were synthesised using a random-effects meta-analysis of the standardised mean difference (SMD) in cardiometabolic health markers (baseline to postintervention) using Review Manager 5.3. Short-term (ST) HIIT (<12 weeks) significantly improved maximal oxygen uptake (VO2 max; SMD 0.74, 95% CI 0.36 to 1.12; p<0.001), diastolic blood pressure (DBP; SMD -0.52, 95% CI -0.89 to -0.16; p<0.01) and fasting glucose (SMD -0.35, 95% CI -0.62 to -0.09; p<0.01) in overweight/obese populations. Long-term (LT) HIIT (≥12 weeks) significantly improved waist circumference (SMD -0.20, 95% CI -0.38 to -0.01; p<0.05), % body fat (SMD -0.40, 95% CI -0.74 to -0.06; p<0.05), VO2 max (SMD 1.20, 95% CI 0.57 to 1.83; p<0.001), resting heart rate (SMD -0.33, 95% CI -0.56 to -0.09; p<0.01), systolic blood pressure (SMD -0.35, 95% CI -0.60 to -0.09; p<0.01) and DBP (SMD -0.38, 95% CI -0.65 to -0.10; p<0.01) in overweight/obese populations. HIIT demonstrated no effect on insulin, lipid profile, C reactive protein or interleukin 6 in overweight/obese populations. In normal weight populations, ST-HIIT and LT-HIIT significantly improved VO2 max, but no other significant effects were observed. Current evidence suggests that ST-HIIT and LT-HIIT can increase VO2 max and improve some cardiometabolic risk factors in overweight/obese populations.
Pfizer loses appeal over use of branded painkiller pregabalin
Authors: Nigel Hawkes
Journal: BMJ (2016)

Pfizer has failed in its bid to overturn a High Court ruling on the validity of the patents covering its painkiller pregabalin (marketed as Lyrica).

The appeal court upheld the lower court ruling against the company, in which Mr Justice Richard Arnold said that Pfizer had made “groundless claims” that its patent would be infringed unless doctors prescribed Lyrica by brand name as opposed to a generic alternative.1

Pfizer …
Impact of Cytokine Gene Polymorphisms on Risk and Treatment Outcomes of Aplastic Anemia
Authors: Eunyoung Lee, Yun-Gyoo Lee, Inho Kim, Ji-Hyun Kwon, Dong-Yeop Shin, Ji-Yeon Bae, Sung-Soo Yoon, Sung Sup Park, Dong Soon Lee, Myoung Hee Park, Seonyang Park, Byoung-Kook Kim
Journal: Blood (2011)
Phase I study of pemetrexed plus cisplatin in unresectable, advanced gastric carcinoma in Taiwan
Authors: J. Chen, Y. Chao, L. Chen, C. Li, W. Reece, R. Khan, E. Pope, J. C. Otero
Journal: Journal of Clinical Oncology (2006)

14009 Background: Phase I of this Phase I/II study (H3E-AA-S038) was conducted to determine the recommended dose of pemetrexed (PT) when given with cisplatin (Cis) to patients with unresectable, advanced gastric carcinoma. Methods: Patients 18 to 70 years of age, with stage IV disease or post-surgery recurrence, no prior palliative chemotherapy, and an ECOG performance status of 0 or 1 were included. Patients received PT and Cis on Day 1 every 21 days. Cis was dosed at 75 mg/m 2 . PT dosage was planned at 600, 700, 800, and 900 mg/m 2 . Vitamin B12 and folic acid supplementation, and dexamethasone (or equivalent corticosteroid) prophylaxis were required. The initial number of patients to be enrolled per dose level (DL) was 3. If 0/3 patients had dose-limiting toxicity (DLT), PT dose was escalated. If 1/3 patients had DLT, 3 more patients were enrolled at that DL. If ≥2 patients had DLT, the dose was not escalated further. The recommended dose of PT for Phase II was the highest dose at which &lt;2/6 patients experienced DLT. The following toxicities were defined as DLT: death due to toxicity; neutropenia [&lt;0/5 × 10 9 /L for ≥5 days, or &lt;1.0 × 10 9 /L with fever (≥38.5 ºC)]; thrombocytopenia (&lt;10.0 × 10 9 /L, or &lt;50.0 × 10 9 /L with bleeding); AST or ALT &gt;20 × ULN; and non-hematological toxicities of CTC grade 3 or 4 (except nausea and vomiting). Intra-patient dose escalation was not permitted. Results: Sixteen patients were enrolled. The mean (±SD) age of enrolled patients was 52.8 (±10.0) years, and the majority were male (62.5%). At DL1, 0/3 patients experienced DLT. At DL2, 1/6 patients had DLT. At DL3, 3/7 patients had DLT, and so PT dose was not escalated. All DLTs occurred in cycle 1; 2 involved neutropenia, 1 tumor hemorrhage, and 1 hypokalemia. Grade 3/4 toxicities were experienced by 12/16 (75%) patients, including 9 (56%) hematological and 10 (63%) non-hematological events. Five out of thirteen (38%) patients with measurable disease had a RECIST response (2 had a complete response, 1 each at DL1 and DL2; 3 had a partial response, 2 at DL2 and 1 at DL3). At this interim analysis, 2 patients were still on therapy. Conclusions: The recommended dose of PT is 700 mg/m 2 . Phase II will examine response and safety of PT plus Cis in advanced gastric carcinoma. [Table: see text]
Infection With Hepatitis C Virus Genotype 3 Is an Independent Risk Factor for End-Stage Liver Disease, Hepatocellular Carcinoma, and Liver-Related Death
Authors: Brian J. McMahon, Dana Bruden, Lisa Townshend-Bulson, Brenna Simons, Phillip Spradling, Stephen Livingston, James Gove, Annette Hewitt, Julia Plotnik, Chriss Homan, Hannah Espera, Susan Negus, Mary Snowball, Youssef Barbour, Michael Bruce, Prabhu Gounder
Journal: Clinical Gastroenterology and Hepatology (2016)
An Open-Label, Dose–Escalation Phase I Study of Anti-TYRP1 Monoclonal Antibody IMC-20D7S for Patients with Relapsed or Refractory Melanoma
Authors: Danny N. Khalil, Michael A. Postow, Nageatte Ibrahim, Dale L. Ludwig, Jan Cosaert, Siva Rama Prasad Kambhampati, Shande Tang, Dmitri Grebennik, John Sae Wook Kauh, Heinz-Josef Lenz, Keith T. Flaherty, F. Stephen Hodi, Donald P. Lawrence, Jedd D. Wolchok
Journal: Clinical Cancer Research (2016)

Tyrosinase-related protein-1 (TYRP1) is a transmembrane glycoprotein that is specifically expressed in melanocytes and melanoma cells. Preclinical data suggest that mAbs targeting TYRP1 confer antimelanoma activity. IMC-20D7S is a recombinant human IgG1 mAb targeting TYRP1. Here, we report the first-in-human phase I/Ib trial of IMC-20D7S.
A phase I trial of SAR650984, a CD38 monoclonal antibody, in relapsed or refractory multiple myeloma.
Authors: Thomas G. Martin, Karl Hsu, Stephen Anthony Strickland, Martha Jane Glenn, Joseph Mikhael, Eric Charpentier
Journal: Journal of Clinical Oncology (2014)

8532 Background: SAR650984 (SAR) is a naked humanized IgG1 monoclonal antibody that binds to the CD38 receptor. SAR kills tumor cells via ADCC, CDC, direct apoptosis without secondary crosslinking and allosteric inhibition on CD38 enzymatic activity. Data on relapsed /refractory multiple myeloma (RRMM) patients (pts) in the dose escalation phase of the study are reported. (NCT01084252). Methods: SAR was given IV weekly (QW) or every 2 weeks (Q2W). Dose levels (DL) 0.3, 1, 3, 5, 10 and 20 mg/kg Q2W and 10 mg/kg QW using the classic 3+3 design were evaluated. Results: 35 pts with RRMM were treated; median age 64 yrs (40-76); median lines of therapy were 6 (2-14), 34/35 received an IMiD and a proteasome inhibitor (57% had carfilzomib (C) and/or pomalidomide (P). MTD was not reached at any DL. Adverse events in ≥ 10% of pts at all DL, regardless of causality, were fatigue (48.6%), nausea (34.3%), pyrexia (28.6%), anemia (28.6%), cough (25.7%), headache (25.7%), upper respiratory infection and chills (22.9%), dyspnea (20%), constipation (17.1%), diarrhea and vomiting (14.3%) and bone pain, chest discomfort, muscle spasms, thrombocytopenia and hypokalemia in 11.4% of pts. SAR related ≥ G 3 adverse events included pneumonia (n = 3), with hyperglycemia, hypophosphatemia, pyrexia, apnea, fatigue, thrombocytopenia and lymphopenia in 1 pt each. Investigator assessment by EBMT response criteria (ORR ≥ PR) among 34 evaluable pts was 24% (CR n = 2, PR n = 6). Responses occurred at all DL ≥ 1 mg/kg. Clinical benefit response (≥ MR) was 29% with 41% SD. In the ≥10 mg/kg cohort ORR was 33% (n =6/18) and CBR was 39% (n =7/18). The time to response was 4.6 weeks and time on treatment was 9.9 weeks (2-81). 10 pts remain on treatment. The expansion cohort dose was selected based on efficacy, safety, and receptor occupancy data. Conclusions: The MTD of SAR was not reached. SAR demonstrates encouraging and durable single agent efficacy in heavily pretreated RRMM pts, including those with prior (C) and (P) and warrants further evaluation. Clinical trial information: NCT01084252. Response EBMT * All DL (n=34) DL ≥10mg/kg (n=18) ORR (8) 24% (6) 33% CBR (10) 29% (7) 39% PD (10) 29% (4) 22% SD (14) 41% (7)39% MR (2) 6% (1) 5% PR (6) 18% (4) 22% CR (2) 6% (2) 11% *Investigator assessment of response as of Dec 31, 2013.
Clinical features of ulcerative colitis-associated colorectal cancer in Japan: an analysis of 169 cases over 20 years
Authors: T. Watanabe, T. Konishi, T. Muto, K. Kotake, H. Nagawa
Journal: Journal of Clinical Oncology (2006)

13544 Background: Development of colorectal cancer is a well-known long-term complication of ulcerative colitis (UC). However, specific clinical features of UC-associated colorectal cancer have been controversial mainly due to the small number of cases, especially in the Asian countries. This study aims to clarify the clinicopathological features of UC-associated colorectal cancer compared with non-UC-associated colorectal cancer in Japan, using a large nationwide database. Methods: All patients pathologically diagnosed as colorectal cancer from 1978 to 1998 were extracted from the nationwide database, “Multi-Institutional Registry of Large-Bowel Cancer in Japan”, which covers almost 10% of all colorectal cancers in Japan. Clinicopathological factors were compared between those associated with UC and the others. Survival analysis in each TNM stage was performed using the Kaplan-Meier method. Results: Among 108,536 cases of colorectal tumors registered from 1978 to 1998, a total of 169 cases of UC-associated colorectal cancers were identified. All cases were from the Asian population. UC-associated cases showed higher prevalence of females, younger age, higher incidence of multiple cancers, and higher incidence of mucinous adenocarcinomas. On the other hand, there were no differences in tumor sites, family history of colorectal cancer, lymph node metastasis, distant metastasis, TNM stage, and CEA level adjusted by TNM stage between the two groups. Survival analysis revealed poorer prognosis in UC-associated colorectal cancers at TNM stage 3. Conclusions: UC-associated colorectal cancer showed unique histological features compared with usual colorectal cancer. The survival of UC-associated colorectal cancer with lymph node metastasis was poorer than usual colorectal cancer, and therefore, intensive adjuvant therapy and close follow-up is needed after surgery in this patient group. No significant financial relationships to disclose.