tbuckley/cabot-search huggingface dataset:
Epidemiologic findings of non-Hodgkin lymphoma (NHL) in Puerto Rico (PR).
Authors: Jose Luis Ortega, Maribel Tirado-Gomez, Fernando Cabanillas, Noridza Rivera-Rodriguez, Carlos Torres, Karen Ortiz
Journal: Journal of Clinical Oncology (2013)

e19505 Background: NHL was the 6th leading cause of cancer among USA Hispanics from 2005-2009. There is limited literature about lymphoma among Hispanics outside USA. The goal of this study is to assess the incidence, trends, survival and histological distribution in a population of Puerto Ricans and compare the results with USA. We report data on 3,184 pts diagnosed with lymphoma from the PR Cancer Center Registry during 2004-2009. Methods: Rates of sex-specific, age-adjusted incidence (AAIR) with 95% CI were estimated and standardized by age-adjustment according to the world standard population. The annual percent change (APC) using joint point regression analysis was determined. Data was compared with the SEER Cancer Statistic Review (1975-2009). Results: NHL comprises 82% of lymphomas in PR. As in USA it is the 6th most common cancer in males and the 7th in females. AAIR per 100,000 for NHL in PR was lower as compared to USA: 11.8 for males in PR vs 23.2 in USA, while for females it was 9.8 in PR vs 16.2 in USA. Despite a lower AAIR, there was an increase of 3.2% APC in NHL for PR during 2004-09. When analyzed according to gender, this rise was attributed only to females: 6.3% increase vs 0.5% in males. In contrast, in USA a decreasing trend in APC (-0.8%) was seen for females. B cell lymphomas in PR comprise 92% of NHL and 90% in USA. DLBCL represents 53% of all B cell-NHL in PR which is markedly higher than the 28% reported in USA. Follicular NHL in PR represents 22% of all NHL, in contrast to 32% in USA. There is a noticeable difference in the distribution of T cell lymphoma subtypes in PR as compared with USA, with a higher number of cases of anaplastic large cell and cutaneous T cell lymphomas and a lower frequency of angioimmunoblastic T cell lymphomas in PR. In terms of relative survival rate (RSR), our results are comparable to USA. Follicular NHL has a 5 year RSR of 74% in PR vs 75% in USA and DLBCL has a 5 year RSR of 47% in PR, vs 50% RSR in USA. Conclusions: Despite a lower AAIR, a significant increasing trend of NHL was observed in PR and we determined this to be exclusively observed among females. We also identified marked differences between the distribution of histologic subtypes of NHL in PR and USA. We plan to assess which histologic subtypes are increasing and in which regions of the island.
Functional Interpretation of Coronary Stenoses by Cardiac CT and the Many Ways to Skin That Cat
Authors: Koen Nieman, Y. Chandrashekhar
Journal: JACC. Cardiovascular imaging (2019)

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Coronary computed tomography (CT) angiography (CTA) has become an established diagnostic technique for the assessment of coronary artery disease (CAD). As a sensitive technique, it can reliably confirm the absence of CAD, but it has a low positive predictive
Phase I immunotherapy trial using glioblastoma apoptotic body-pulsed dendritic cells.
Authors: Christopher L. Moertel, Michael Olin, Tambra Dahlheimer, Michael Gustafson, Darin Sumstand, David McKenna, Walter Low, David Nascene, Allen Dietz, John Ohlfest
Journal: Journal of Clinical Oncology (2012)

2546 Background: We recently reported that tumor cell vaccines cultured in 5% oxygen (O 2 ) had enhanced the immunogenicity relative to those grown in standard atmospheric O 2 . In order to develop an “off-the-shelf” source of whole cell antigen we screened a panel of primary glioblastoma (GBM) cell lines, leading to identification of (GBM6) as an ideal candidate. GBM6 was extensively characterized and shown to express glioma-associated antigens (IL13Ra2, Sox2, Epha2, etc.). A Phase I clinical trial was initiated to evaluate the safety and feasibility of a vaccine consisting of dendritic cells (DC) pulsed with apoptotic bodies from GBM6 grown in 5% O 2 . Methods: Patients ranging from 3 to 71 years with recurrent GBM (n=6) or ependymoma (n=1) were enrolled. Monocytes were collected via apheresis, matured into DC and pulsed with apoptotic bodies derived from GBM6. The first three patients received escalating doses of DC (5x10 6 , 10x10 6 , and 15x10 6 ), the remainder received 15 x 10 6 DC. Pulsed dendritic cellswere injectedsubcutaneously into the supra-scapular region. Imiquimod cream was applied at the injection site just prior to vaccination and 24 hours later. The vaccine schedule dictated administration every 2 weeks for 8 weeks (total of 5 doses) then monthly to progression or a total of 52 weeks. Prior to each vaccination, patients met eligibility parameters and had no progression on MRI. Patients were imaged monthly and blood was drawn to evaluate toxicity and immune response. Results: No vaccine-related toxicity has been reported. Time to progression ranges from 6.5 weeks for the patient treated at the first dose level to 35 weeks for one patient receiving 15 x 10 6 DC. The latter patient experienced a partial response at 20 weeks. Two patients have stable disease at 18.5 and 28 weeks, respectively. One patient was not evaluable. Flow cytometric analysis demonstrated expansion of central memory T cells amidst declining effector memory cells following vaccination in three patients at a dose of 15x10 6 DC. Conclusions: Apoptotic body-pulsed DC vaccination was well tolerated and preliminarily demonstrated clinical activity but a minimum of 15x10 6 DC was required for a modulation of central memory T cells.
Inflammatory cytokines shape a changing DNA methylome in monocytes mirroring disease activity in rheumatoid arthritis
Authors: Javier Rodríguez-Ubreva, Carlos de la Calle-Fabregat, Tianlu Li, Laura Ciudad, Maria L Ballestar, Francesc Català-Moll, Octavio Morante-Palacios, Antonio Garcia-Gomez, Raquel Celis, Frances Humby, Alessandra Nerviani, Javier Martin, Costantino Pitzalis, Juan D Cañete, Esteban Ballestar
Journal: Annals of the Rheumatic Diseases (2019)

Objective Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly targets joints. Monocytes and macrophages are critical in RA pathogenesis and contribute to inflammatory lesions. These extremely plastic cells respond to extracellular signals which cause epigenomic changes that define their pathogenic phenotype. Here, we interrogated how DNA methylation alterations in RA monocytes are determined by extracellular signals. Methods High-throughput DNA methylation analyses of patients with RA and controls and in vitro cytokine stimulation were used to investigate the underlying mechanisms behind DNA methylation alterations in RA as well as their relationship with clinical parameters, including RA disease activity. Results The DNA methylomes of peripheral blood monocytes displayed significant changes and increased variability in patients with RA with respect to healthy controls. Changes in the monocyte methylome correlate with DAS28, in which high-activity patients are divergent from healthy controls in contrast to remission patients whose methylome is virtually identical to healthy controls. Indeed, the notion of a changing monocyte methylome is supported after comparing the profiles of same individuals at different stages of activity. We show how these changes are mediated by an increase in disease activity-associated cytokines, such as tumour necrosis factor alpha and interferons, as they recapitulate the DNA methylation changes observed in patients in vitro. Conclusion We demonstrate a direct link between RA disease activity and the monocyte methylome through the action of inflammation-associated cytokines. Finally, we have obtained a DNA methylation-based mathematical formula that predicts inflammation-mediated disease activity for RA and other chronic immune-mediated inflammatory diseases.
Comparison of the characteristics and clinical course of 677 patients with metastatic lung cancers with mutations in KRAS codons 12 and 13.
Authors: Helena Alexandra Yu, Camelia S. Sima, Ronglai Shen, Samantha Lindsay Kass, Mark G. Kris, Marc Ladanyi, Gregory J. Riely
Journal: Journal of Clinical Oncology (2013)

8025 Background: Patients (pts) with KRAS mutant lung cancers have a shorter survival compared to pts with KRAS/EGFR wild type tumors (Johnson et al, Cancer 2012). Whether outcomes for patients with KRAS mutant metastatic lung cancers differ by smoking status or specific amino acid substitution is unknown. In order to understand the impact of KRAS mutation subtype in the metastatic setting, we analyzed a large cohort of patients with KRAS mutant metastatic lung cancer. Methods: We identified all pts with KRAS mutant metastatic or recurrent lung cancers from Feb 2005 to Aug 2011. KRAS mutation type, clinical characteristics, and outcomes from diagnosis were obtained from the medical record. A multivariate cox proportion hazard model was used to identify factors associated with overall survival. Results: KRAS mutations were identified in 677 pts (53 at codon 13, 624 at codon 12). Median age: 66 (range 31-89), women: 62%, never smokers: 7%. Pts with transition mutations (n=157) were more likely to be never-smokers (p&lt;0.0001). There was no difference in outcome for pts with KRAS transition versus transversion mutations (p=1) or when comparing current/former smokers to never smokers (p=0.33). There was no difference in overall survival (OS) when comparing specific amino acid substitutions (G12C=366, G12V=141, G12D=114, G12A=68, G13C=27, G13D=23, G12S=19, G12F=11)(p=0.20). Pts with KRAS codon 13 mutant tumors had inferior OS compared to pts with codon 12 mutant tumors, median 13 months (mo) (95% CI 13-17 mo) and 16 mo (95% CI 9-16 mo), respectively (p=0.009). There was no difference in frequency of receiving platinum-based chemotherapy or chemotherapy of any kind between pts with codon 12 and 13 mutant tumors. In a multivariate Cox model which included age, gender and smoking status, KRAS codon 13 mutation was associated with worse overall survival than KRAS codon 12 mutation (HR 1.52 95% CI 1.11-2.08 p=0.008). Conclusions: Among pts with KRAS mutant metastatic lung cancers, smoking history, and specific amino acid substitution do not affect outcome. Patients with KRAS codon 13 mutant metastatic lung cancer have shorter survival compared to pts with KRAS codon 12 mutant lung cancer.
The natural history, treatment pattern, and survival of the patients with micropapillary bladder.
Authors: Jue Wang
Journal: Journal of Clinical Oncology (2012)

e15015 Background: Micropapillary bladder carcinoma (MPBC) is a rare variant of urothelial carcinoma. The objective of this study was to examine the epidemiology, natural history, and prognostic factors of MPBC using population-based registry. Methods: The Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify cases of MPBC by tumor site and histology codes. The clinical, demographic characteristics, treatment and survival of MPBC were examined. Results: A total of 98 cases of histology confirmed MPBC were identified between 2001 and 2007, this accounted for approximately 0.01% of all primary bladder tumors during the study period. Median age of the patients was 72 years (range 26-95). Of all the patients with MPBC, 56.1% had muscle invasive disease; 75.5% of patients had poorly or undifferentiated histology. A total of 30.6% of all patients (2.3% superficial disease; 52.7% of muscle-invasive MPBC) had radical or partial cystectomy. By logistic regression analysis, nonmuscle-invasive MPBC (OR 62.5, 95% CI 7.2-542.3) was associated with lower rate of utilization of cystectomy. The 1-, 3- and 5-year overall survival rate of MPBC were 84.5%, 57.3% and 42.3%. In multivariate analysis, tumor stage (HR 4.7, 95% CI 1.0-21.8) was found to be the only significant predictor for cancer-specific survival. Conclusions: The optimal therapy for MPBC remains undermined. Emphasis on early detection is needed to improve the outcome for patients with this malignancy.
Single executive team will run trust and CCG in Croydon
Authors: Nigel Hawkes
Journal: BMJ (2019)

In a move that seems to disregard the long established split between purchasers and providers, the NHS in Croydon, in south London, has appointed the same man to run both the local hospital trust and the clinical commissioning group.

Since 1991 the NHS in England has been divided between commissioners, who plan and pay for care, and providers, who deliver it. In its current incarnation the commissioners are the CCGs and the providers the hospital trusts and the private sector. The original hope was that this would improve efficiency through an internal market.

Croydon Health Services NHS Trust announced on 1 August that Matthew Kershaw, previously chief executive of East Kent Hospitals University NHS Foundation Trust, will become the trust’s chief executive and at the same time become the leader of Croydon CCG. This …
Safety profile of recombinant poxviral TRICOM vaccines.
Authors: Joseph W. Kim, Jennifer L. Marte, Nishith K. Singh, Christopher Ryan Heery, Ravi Amrit Madan, Mary Pazdur, Sheri McMahon, Myrna Rauckhorst, Jeffrey Schlom, Philip W. Kantoff, James L. Gulley
Journal: Journal of Clinical Oncology (2013)

e16036 Background: Recombinant (rec) poxviruses have been developed as therapeutic cancer vaccines. A multi-institutional, randomized phase II trial of poxviral vaccine, PROSTVAC-V/F, suggested an improvement in median overall survival in men with metastatic castration resistant prostate cancer. A phase III trial in this same population is accruing. Accumulating data suggest a favorable safety profile of the poxviral vaccines (vacs). Methods: We reviewed all vaccine injections (inj) from 297 patients (pts) in 9 clinical trials involving poxviral vaccines. Vacs consisted of rec vaccinia and rec fowlpox encoded with 3 human costimulatory molecules (TRICOM), and a) prostate specific antigen, or b) carcinoembryonic antigen +/-mucin-1. Vacs were administered at doses between 1.2x10 8 to 2x10 9 pfu, subcutaneously, in all pts. 21 pts were also vaccinated intra-tumorally. 84 pts received concurrent treatments, such as radiation, celecoxib, ipilimumab, samarium-153, or flutamide in 4 of these trials. All 9 trials involved granulocyte-macrophage colony-stimulating factor (GM-CSF), or rec fowlpox encoding GM-CSF as an immune adjuvant. We report the grade &gt;=2 adverse events (AEs) at least possibly attributed to vaccine. Results: A total of 1,793 poxviral inj were given. 33% (593) of all inj were associated with grade &gt;=2 vaccination emergent AEs. Of those, 25.3 % (454) were local inj site reactions; none serious. There was no contact transmission or inadvertent inoculation. One patient experienced grade 4 myocardial infarction and thrombotic thrombocytopenic purpura (TTP) reported as possibly related to vaccine. Below is the summary of AEs. Conclusions: Recombinant poxviral TRICOM vaccines appear safe and well tolerated at a broad range of doses, routes of administration and in combination with other treatments. Clinical trial information: NCT00081848, NCT00088413, NCT00060528, NCT00060528, NCT00078585, NCT00096551, NCT00113984. [Table: see text]
Awareness and attitude of cancer patients about participation in clinical research (CR) in Saudi Arabia.
Authors: Nagham Ramzi Sheblaq, Sara Traifi, Moahmmed Al Sakiani, Ahmed Gasmelseed, Mostafa A Abolfotouh, Abdul Rahman Jazieh
Journal: Journal of Clinical Oncology (2013)

e17528 Background: Enrollment of patients in CR may be impacted by their levels of awareness and attitude toward participation. Our study aims at assessing the awareness and willingness to participate in CR and identifying the barriers and influencing factors for participation. Methods: A cross-sectional study was performed using an interview-based questionnaire composed of close-ended questions conducted by trained research coordinators. Descriptive statistics, univariate and multivariate analyses were applied. Results: A total of 300 patients were enrolled in the study with a median age of 53.6 (42.2 - 64.0), and 188 patients (62.67%) were females. The majority of patients 289 (97.31%) were not aware of what is institutional review board. On the other hand, 226 (75.33%) showed interest in CR participation, if offered. The trust in treating physician (88.33 %) and the belief that participation in CR offers a better chance of cure (73.14%) were the two most important influencing factors to participate, while the preference of receiving standard treatment (43.13%) and the unknown efficacy of treatment (40.32%) were the top two barriers to participate. In univarate analyses, patients younger than 45 years (p&lt;0.015) and those with higher education (more than middle school) (p&lt;0.022) were significantly more interested in CR participation. However; in a multivariate analysis, higher education was the only significant predictor of interest to participate (p&lt;0.023). Conclusions: There is an apparent gap in cancer patients’ awareness about CR. However, there is an obvious interest in participation in CR especially in patients with higher education level. Enhancing public awareness is crucial to improve CR participation.
Disparities in breast cancer among 236,101 patients in Florida
Authors: C. P. Bowen-Wells, W. E. Sumner, F. Moffat, E. Avisar, D. Fraceschi
Journal: Journal of Clinical Oncology (2006)

10790 Background: For minorities with breast cancer, access to healthcare has been an issue. A number of studies have reported racial differences in the pattern of care for women with breast cancer. A recent publication in New England Journal of Medicine indicated that the trend has narrowed between whites and black. In our institution we have noted a persistent higher rate of advanced breast cancer in minority patients. Studies have also showed that minority patients present with more advance disease and are more likely to have receptor negative tumors. Minority patients have higher mortality than whites. Younger minorities appear to do worse than older minorities as a result of lack of insurance. Minorities are less likely to be part of clinical trials. Method: We reviewed the Florida Cancer Data System (FCDS), a large cancer registry. 236,101 cases of breast cancer patients were identified between 1981–1992. Comparisons were made by Chi Square test. Results: Ninety one percentages (91%) of the patients were Whites, 6.8% were Blacks and 2.2% represented all others. Most patients presented with localized disease: Whites had 49%; Blacks had 36% and the other minority 36.3%. Blacks had a significantly higher incidence of regional disease (see figure), and had the highest percentage of metastatic disease at presentation (p &lt; 0.01). Conclusion: Disparities in breast cancer care still clearly exist amongst ethnic group in Florida. The disparities are resulting in higher mortality among non-whites as compared to whites. Better results could be achieved with sets at prevention, education about early detection, screening and access. No significant financial relationships to disclose.
Team illness prevention strategy (TIPS) is associated with a 59% reduction in acute illness during the Super Rugby tournament: a control–intervention study over 7 seasons involving 126 850 player days
Authors: Martin Schwellnus, Charl Janse van Rensburg, Helen Bayne, Wayne Derman, Clint Readhead, Rob Collins, Alan Kourie, Jason Suter, Org Strauss, Nicola Sewry, Esme Jordaan
Journal: British Journal of Sports Medicine (2019)

Objectives To determine whether a team illness prevention strategy (TIPS) would reduce the incidence of acute illness during the Super Rugby tournament. Methods We studied 1340 male professional rugby union player seasons from six South African teams that participated in the Super Rugby tournament (2010–2016). Medical staff recorded all illnesses daily (126 850 player days) in a 3-year control (C: 2010–2012; 47 553 player days) and a 4-year intervention (I: 2013–2016; 79 297 player days) period. A five-element TIPS was implemented in the I period, following agreement by consensus. Incidence rate (IR: per 1000 player days; 95% CI) of all acute illnesses, illness by main organ system, infectious illness and illness burden (days lost due to illness per 1000 player days) were compared between C and I period. Results The IR of acute illness was significantly lower in the I (5.5: 4.7 to 6.4) versus the C period (13.2: 9.7 to 18.0) (p&lt;0.001). The IR of respiratory (C=8.6: 6.3 to 11.7; I=3.8: 3.3 to 4.3) (p&lt;0.0001), digestive (C=2.5: 1.8 to 3.6; I=1.1: 0.8 to 1.4) (p&lt;0.001), skin and subcutaneous tissue illness (C=0.7: 0.4 to 1.4; I=0.3: 0.2 to 0.5) (p=0.0238), all infections (C=8.4: 5.9 to 11.9; I=4.3: 3.7 to 4.9) (p&lt;0.001) and illness burden (C=9.2: 6.8 to 12.5; I=5.7: 4.1 to 7.8) (p=0.0314) were significantly lower in the I versus the C period. Conclusion A TIPS during the Super Rugby tournament was associated with a lower incidence of all acute illnesses (59%), infectious illness (49%) and illness burden (39%). Our findings may have important clinical implications for other travelling team sport settings.
Clinical outcome (CO) and predictive factors (PRE) evaluation of young (≤ 60 years) castration-resistant prostate cancer (CRPC) patients, treated with docetaxel (DOC): Preliminary results of an Italian multicenter retrospective study (CYCLOP study).
Authors: Orazio Caffo, Cinzia Ortega, Giuseppe Di Lorenzo, Francesca La Russa, Salvatore Luca Burgio, Caterina Messina, Gaetano Facchini, Roberto Iacovelli, Michele Lodde, Franco Morelli, Francesco Massari, Giuseppe Procopio, Fable Zustovich, Giovanni Lo Re, Cristina Pegoraro, Teresa Gamucci, Giovanni L. Pappagallo, Antonello Veccia, Francesca Maines, Enzo Galligioni
Journal: Journal of Clinical Oncology (2013)

e16031 Background: CRPC is rare in pts ≤ 60 yrs and clinical outcomes of these pts are not clearly defined despite there is a common feeling of a worse prognosis for them. The present study is aimed to assess CO and PRE in this specific population. Methods: In this multicentric retrospective study, after Ethical Committee approval, we have reviewed the clinical records of all &lt; 60 yrs CRPC pts from participating institutions, treated with DOC. We recorded the pre and post-DOC clinical history, the DOC treatment details and outcomes. We have also assessed the ability of a series of selected 18 clinical factors to predict DOC response through a logistic regression analysis. Continuous variables were categorized by quartiles and chosen for the initial model after a univariate chi-square analysis. Results: To date we have collected a consecutive series of 98 pts from 16 Italian hospitals. The median age was 57 yrs (range 41-60). The median baseline PSA was 84 ng/ml (range 2-2721); 93% of the pts had bone metastases while 49%, 9%, and 13% showed nodal, liver and lung metastases, respectively. All but 8 pts received DOC with a 3-week standard schedule: the median number of received DOC courses was 8 (range 1-14). The main grade 3-4 toxicities were anemia (4 pts), neutropenia (15 pts), febrile neutropenia (1 pt), peripheral neuropathy(1 pt). A PSA reduction &gt; 50% was observed in 61% of the pts while 14% and 7% of the cases showed a partial and complete response, respectively. Having a Gleason score (GS) &lt;8 [p= 0.032], a hemoglobin initial value &gt;12 [p= 0.052], no nodal involvement [p= 0.101], resulted to be independently predictive of a PSA reduction &gt; 50%. The median PFS and OS were 7 mos and 19 mos, while the 1-year PFS and OS rates were 17.3% and 70%, respectively. Conclusions: From these preliminary results, we failed to confirm a worse prognosis for younger CRPC since their survival outcomes are similar to those observed in the pivotal trials. Low GS, absence of nodal involvement and good hemoglobin levels are the only predictive factors.