tbuckley/cabot-search huggingface dataset:
Influence of physical activity on recurrence and survival of colorectal cancer patients: A meta-analysis.
Authors: Gaetan Des Guetz, Thierry Bouillet, Bernard Uzzan, Kader Chouahnia, Patrick Nicolas, Laurent H. Zelek, Jean F. Morere
Journal: Journal of Clinical Oncology (2013)

1583 Background: Colorectal cancer (CRC) predominates in developed countries among sedentary populations. A meta-analysis (MA) showed that physical activity (PA) decreased the incidence of new cases of CRC. The impact of PA on recurrence and mortality of non-metastatic CRC patients is still controversial. Methods: We performed a literature-based meta-analysis of all published observational studies, using the following keywords (colorectal cancer, physical activity, survival) in PubMed and EMBASE. We searched for a dedicated MA in the Cochrane Library (none found). We cross-checked all references. Pre- and post-diagnostic PA levels were assessed with MET (Metabolic Equivalent Task). Usually, high PA levels corresponded to &gt; 17 MET hours/week. Overall survival (OS) and cancer-specific survival (CSS) were assessed by means of Hazard Ratios (HRs) with their 95 % Confidence Interval (CI). We pooled adjusted HRs since the variables of adjustment were almost identical between studies (age, sex, BMI, tobacco use, alcohol and red meat consumptions ). By convention, when higher PA levels were associated to an improved survival compared with lower PA levels, HRs for detrimental events were &lt; 1. We used EasyMA software. We used fixed effect model whenever possible and random effect model only in case of between-study heterogeneity. Results: Eight studies (11298 participants) published from 2006 to 2013 met the inclusion criteria, representing 3110 males and 3710 females, 3072 colon and 1318 rectum cancers. Mean age was 67 years (range 21-82 years). HR CSS for post-diagnostic PA (higher PA level vs. lower) was 0.61 (CI: 0.44-0.86; random effect model). The corresponding HR for OS was 0.62 (CI: 0.54-0.71). HR CSS for pre-diagnostic PA was 0.80 (CI: 0.69-0.92). The corresponding HR for OS was 0.74 (CI: 0.63-0.86). Conclusions: This MA is the first to show that higher PA levels are associated with a better CSS, suggesting that sustained PA should be advised for non-metastatic CRC patients. OS also significantly improved, not surprisingly since PA should reduce risk of cardio-vascular events. These findings should be tempered by the rather small number of studies included.
Salvage chemotherapy using irinotecan and temozolamide in pediatric and adult populations with relapsed Ewing sarcoma.
Authors: Samer Salah, Yat Hang To, Taleb Ismaeel, Omar Khzouz, Iyad Yasin Sultan, Sameer Yaser, Anoud Zaid Alnsour, Ramiz Abuhijlih, Omar Shahin, Rasha Aldouri, Jeremy Lewin
Journal: Journal of Clinical Oncology (2019)

e22500 Background: Irinotecan and temozolomide (IT) is a widely used regimen for relapsed Ewing Sarcoma (ES), although studies are largely limited to the paediatric population. We aimed to compare the tolerability and efficacy of IT between paediatric and adult patients. Methods: We retrospectively reviewed paediatric (&lt; 18 years) and adult patients treated with salvage IT chemotherapy at two institutions from March, 2010 to June, 2018. Toxicities were graded according to common terminology criteria of adverse events (CTCAE v. 4.03) and compared using the Chi Square test. Responses were interpreted by Response Evaluation Criteria in Solid Tumors (RECIST). The Kaplan-Meyer method was used to estimate progression free survival (PFS); survival comparisons were carried out by the Log-rank test. Results: Fifty-three patients were included ( n= 16 paediatric; n= 37 adult). Median age was 20 (range, 5 – 45 years). A total 236 IT cycles were delivered (median = 4, range:1-7). IT was given as second-line ( n= 34; 64%) or ≥third-line ( n= 19; 36%). There was no difference in ≥grade 3/4 haematologic toxicity between paediatric and adult patients (31% vs. 35% respectively; p= 0.76), whilst febrile neutropenia was observed in two (4%) patients (one adults and one paediatric). The frequency of diarrhoea of any grade was similar (38% in each group). Of 43 patients assessable for response, 12 (28%) had objective response (1 CR, 11 PR), 19 (44%) had disease progression and 12 (28%) had stable disease. Objective response rate did not differ between the two groups (36% in paediatrics vs. 25% in adults; p = 0.47). Median PFS was superior in paediatrics vs. adults (7.4 vs. 2.1 months, p = 0.001). Superior PFS for the paediatric population was observed in both, the second-line (6.2 vs. 2.2 months; p= 0.060) and ≥third-line setting (7.4 vs. 1.2 months, p= 0.014). Conclusions: IT is an effective salvage regimen for ES, with favourable toxicity and equally observed objective responses in paediatric and adult populations. The observed superior PFS for the paediatric cohort requires further confirmation in a larger prospective study.
Expression of T-cell populations and molecular markers of human myocardium with checkpoint-induced myocarditis.
Authors: Abdulrazzak Zarifa, Peter Y. Kim, Susan Gilchrist, Cezar Iliescu, Maria E. Suarez-Almazor, Juan Lopez-Mattei, Dinu Valentin Balanescu, Teodora Donisan, Nick Palaskas, Ankit Upadhyay, Rohit Moudgil, Bihong Zhao, Maximillian Buja, Jean-Bernard Durand
Journal: Journal of Clinical Oncology (2019)

79 Background: Checkpoint Inhibitors have become first line therapy for a variety of solid and liquid malignancy. Immunotherapeutic agents predominantly target CTLA-4 and PD-L1. Efficacy has been demonstrated, and toxicities, especially cardiac manifested as myocarditis. The incidence of myocarditis is relatively low, fatality with monotherapy approaches 50% and with dual Immunotherapy is over 75%. No screening biomarkers or cardiac imaging predict a priori whom will develop myocarditis, nor which patients will be at risk. The frequency of these targets are unknown in the human heart. Methods: We present a case study of a patient with a diagnosis of urothelial carcinoma to lung and lymph nodes treated with systemic nivolumab plus NKTR after cycle 2 he presented with one week history of shortness of breath and hemodynamically unstable complete heart block requiring temporary transvenous pacemaker. Initial Troponin = 356, BNP = 2106. Given high suspicion for cardiovascular disease and or myocarditis, a left heart angiogram, right heart catheterization and endomyocardial biopsy of right ventricle were performed. RV biopsies were obtained percutaneously from right internal jugular approach with fluoroscopic guidance. Pulmonary capillary wedge pressure was 23mmHg. Persistent complete heart block was present during weaning attempts from temporary pacemaker and a percutaneous dual chamber pacemaker was implanted. Results: Coronary angiogram showed non obstructive disease, endomyocardial biopsy revealed lymphocytic infiltrate with necrosis based on Dallas Criteria. Immunohistochemistry showed, predominance of CD3,CD4,CD8,CD20,CD68 and PD-L1 staining was grossly positive compared to control samples. The patient was treated with methylprednisone 1mg/kg IV BID, plasmapheresis times 5 cycles, mycophenolate mofetil 500mg IV BID with resolution of symptoms and discharged to home. Conclusions: We present a patient with nivolumab induced myocarditis complicated with myocarditis and complete heart block. The pathological approach of T-Cell phenotyping is unique and identifies a novel approach to precision driven diagnosis, the incidence of PD-L1 expression in the human heart is unknown.
Differential expression of the 150-kd oxygen-regulated protein (ORP150) in benign, pre-malignant and malignant breast tissue
Authors: A. Stojadinovic, J. Hooke, C. D. Shriver, A. Kovatich, A. Nissan, S. Ponniah, G. E. Peoples, M. Moroni
Journal: Journal of Clinical Oncology (2006)

10770 Background: Heat shock protein, ORP150, plays a role in hypoxia/ischemia and angiogenesis. Preliminary studies demonstrate increased ORP 150 expression in human cancer, and associate its over expression with aggressive tumor biology. This study further evaluates ORP150 expression in different stages of breast cancer, such as benign, pre-malignant and malignant breast lesions and correlates it with clinical-pathological data. Methods: Sixty-six prospectively collected paraffin-embedded breast tissue sections were reviewed for diagnostic confirmation (normal, n=25; DCIS, n=20; invasive breast cancer (Ca), n=21) and stained using ORP150 antibody immunohistochemistry (IHC). Antibody-staining levels in the benign, DCIS and invasive component of each lesion were reviewed independently by two pathologists and scored: 0 (lowest) to 3+ (highest). Clinical-pathological data was compared with ORP150 staining using ANOVA or T-Test as appropriate with significance determined by p&lt;0.05. Results: Significant differential ORP150 staining was detected in benign-normal versus benign adjacent to invasive cancer, as well as in benign adjacent to DCIS versus benign adjacent to invasive cancer. ORP150 expression in the invasive portion of the breast cancer correlated significantly with tumor grade and absence of hormone receptor expression, presence of lymphovascular invasion and lymph node metastasis. Conclusions: ORP150 expression in breast cancer is associated with poor prognostic histological factors. As ORP150 is differentially expressed in benign tissue adjacent to invasive cancer, further study is warranted to determine its utility in detecting occult invasive cancer within benign biopsy specimens, as well as its putative role in tumor-stromal cell interactions. [Table: see text] No significant financial relationships to disclose.
A Comprehensive Study of Vesicular and Non-Vesicular miRNAs from a Volume of Cerebrospinal Fluid Compatible with Clinical Practice
Authors: Endika Prieto-Fernández, Ana María Aransay, Félix Royo, Esperanza González, Juan José Lozano, Borja Santos-Zorrozua, Nuria Macias-Camara, Monika González, Raquel Pérez Garay, Javier Benito, Africa Garcia-Orad, Juan Manuel Falcón-Pérez
Journal: Theranostics (2019)

Cerebrospinal fluid (CSF) microRNAs (miRNAs) have emerged as potential biomarkers for minimally invasive diagnosis of central nervous system malignancies.However, despite significant advances in recent years, this field still suffers from poor data reproducibility.This is especially true in cases of infants, considered a new subject group.Implementing efficient methods to study miRNAs from clinically realistic CSF volumes is necessary for the identification of new biomarkers.Methods: We compared six protocols for characterizing miRNAs, using 200-µL CSF from infants (aged 0-7).Four of the methods employed extracellular vesicle (EV) enrichment step and the other two obtained the miRNAs directly from cleared CSF.The efficiency of each method was assessed using real-time PCR and small RNA sequencing.We also determined the distribution of miRNAs among different CSF shuttles, using size-exclusion chromatography.Results: We identified 281 CSF miRNAs from infants.We demonstrated that the miRNAs could be efficiently detected using only 200 µL of biofluid in case of at least two of the six methods.In the exosomal fraction, we found 12 miRNAs that might be involved in neurodevelopment. Conclusion:The Norgen and Invitrogen protocols appear suitable for the analysis of a large number of miRNAs using small CSF samples.
Abstract 14928: Efficacy and Safety of Transradial Multi-vessel Coronary Artery Disease Intervention as Compared With Single Vessel Disease Intervention
Authors: Woong Gil Choi, Seung Woon Rha, Soo Hyun Kim, Byoung Geol Choi, Se Yeon Choi, Dong Joo Oh
Journal: Circulation (2015)

Backgroud: Transradial percutaneous coronary intervention (PCI) has evolved into a viable alternative to the traditional transfemoral approach. Clinical aspects related to transradial PCI on multi-vessel disease have been seldom investigated and reported. The aim of this study is to evaluate safety and efficacy of transradial intervention (TRI) for patients with multi-vessel disease as compared with single vessel disease. Method: A total of 1,690 consecutive patients underwent TRI were entered into multicenter Korean TRI Registry from Nov 2004 to Oct 2010. The patients were divided into two groups; Multi-vessel radial PCI group (n=424 pts) and Single vessel radial PCI group (n= 1266 pts). To adjust potential confounders, propensity score matched (PSM) analysis was performed using the logistic regression model (C-statics: 0.726). After PSM, total of 776 pts (388 pairs) were generated for this analysis. The primary study endpoint was 1-year major adverse cardiac event (MACE) defined as the composite of total death, myocardial infarction, target vessel revascularization (TVR) and stent thrombosis. Result: Baseline characteristics were well balanced between the two groups after PSM adjustment. At 1 year, the incidence of MACE was similar between the two groups (11.0% vs. 10.8 %, p=0.908, table). Although the multi-vessel radial PCI group had a longer procedure time (65.52±30.2 vs. 48.75±25.7 min, p&lt;0.001) than the single-vessel PCI group, however, the incidence of contrast induced nephropathy was similar between the two groups (0.7% vs. 1.0%, p=0.725). Conclusion: In this study, although procedure time was longer in multi-vessel radial PCI group, transradial PCI was safe and effective in patients with multi-vessel disease. It might be favored over femoral artery as a primary access route for complex PCI.
Molecular and metabolic pathways mediating curative treatment of a non-Hodgkin B cell lymphoma by Sindbis viral vectors and anti-4-1BB monoclonal antibody
Authors: Minjun Yu, Iris Scherwitzl, Silvana Opp, Aristotelis Tsirigos, Daniel Meruelo
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Limitations to current therapies for treating non-Hodgkin B cell lymphoma include relapse, toxicity and high cost. Thus, there remains a need for novel therapies. Oncolytic viral (OV) therapy has become a promising cancer immunotherapy because of its potential effectiveness, specificity and long-lasting immunity. We describe and characterize a novel cancer immunotherapy combining Sindbis virus (SV) vectors and the agonistic monoclonal antibody (mAb) to the T cell costimulatory receptor, 4-1BB (CD137). <h3>Methods</h3> A20 lymphoma was transfected with luciferase and tumor cells were inoculated to BALB/c mice. Tumor growth was monitored by IVIS imaging. Tumor bearing mice were treated with Sindbis virus, α4-1BB Ab or SV plus α4-1BB Ab. On day 7 after treatment, splenocytes were harvested and surface markers, cytokines, and transcription factors were measured by flow cytometry or Elispot. Splenic T cells were isolated and RNA transcriptome analysis was performed. Tumor cured mice were rechallenged with tumor for testing immunological memory. <h3>Results</h3> SV vectors in combination with α4-1BB monoclonal antibody (mAb) completely eradicated a B-cell lymphoma in a preclinical mouse model, a result that could not be achieved with either treatment alone. Tumor elimination involves a synergistic effect of the combination that significantly boosts T cell cytotoxicity, IFNγ production, T cell proliferation, migration, and glycolysis. In addition, all mice that survived after treatment developed long lasting antitumor immunity, as shown by the rejection of A20 tumor rechallenge. We identified the molecular pathways, including upregulated cytokines, chemokines and metabolic pathways in T cells that are triggered by the combined therapy and help to achieve a highly effective anti-tumor response. <h3>Conclusions</h3> Our study provides a novel, alternative method for B cell lymphoma treatment and describes a rationale to help translate SV vectors plus agonistic mAb into clinical applications.
Pharmacogenomic (PG) analysis for prediction of individual response to paclitaxel in 5-FU-refractory metastatic gastric cancer: Prediction formula of tumor response using novel marker genes and genotypes associated with the toxicity
Authors: R. Ikeda, K. Yoshida, A. Takagane, A. Tsuburaya, O. Kobayashi, H. Sunouchi, M. Matsukawa, K. Tanimoto, K. Hiyama, M. Nishiyama
Journal: Journal of Clinical Oncology (2007)

2538 Background: Taxanes offer hope for improving outcomes of metastatic gastric cancer patients including 5-FU failure cases, but the response remarkably varies among patients. We conducted this prospective PG study for paclitaxel monotherapy to develop a prediction formula of efficacy and to identify potent genetic markers of toxicity. Methods: Paclitaxel was intravenously given on Days 1, 8, and 15, every 4 weeks in 5-FU failure metastatic gastric cancer patients with typical eligibility criteria. Tumor and blood samples were collected before the initial paclitaxel administration for PG. PK analysis was done on day 1 of cycle 1. Tumor response and toxicity were evaluated by RECIST and CTCAE, respectively. Results: Forty-nine pts were enrolled, and up to date, 48 and 44 pts have been determined for worst toxicity and best tumor response, respectively. Observed response rate was 27.3% (12/44), and common grade 3/4 toxicities were neutropenia (31.3%) and leucopenia (20.8%). PG analysis demonstrated that CYP2C8*1C (w/v=27, v/v=5) and CYP2C8 -411T&gt;C (w/v=24, v/v=10) were weakly associated with grade 3/4 leucopenia (p=0.087 and 0.092), and CYP2C8 IVS7+49T&gt; A (w/v=9, v/v=6) might correlate with grade 3/4 anemia (p=0.039), although none of them correlated with any PK parameter. We identified 4 novel potent marker genes (SEPT5, MARN2, PER3, and PISA3) for paclitaxel efficacy in vitro through microarray expression analysis, and then successfully developed the best linear models, which converted the quantified expression data into objective clinical response, in terms of best tumor response (r=0.985, AICS=-5.269) and overall survival (r=0.980, AICS=6.953), using 15 and 13 data sets of gene expression and clinical response, respectively. At present, utility-confirmation analyses using other clinical samples appeared to show that the formulae could accurately predict tumor response. Conclusions: Polygenetic strategies using several known polymorphisms for toxicity and a prediction formula using 4 novel genes for efficacy would be of predictive value for individual response to paclitaxel. No significant financial relationships to disclose.
Pension tax: Hancock urges doctors not to retire and pledges to “fix” crisis by 2020
Authors: Gareth Iacobucci
Journal: BMJ (2019)

England’s health secretary, Matt Hancock, has urged doctors not to take early retirement because of punitive pension tax charges and has promised to consult with the profession and the Treasury to fix this “very serious” problem by the start of the next financial year.

In response to growing concern about the impact of the charges, the government announced a plan in June to allow senior clinicians to halve their pension contributions to avoid large tax bills.1 The NHS pension scheme does not currently offer any flexibility in the rate at which pensions build, and the highest earning consultants contribute 14.5% of their pensionable pay each month.

But last week NHS trusts reported …
The HPV16 Genome Is Stable in Women Who Progress to <i>In Situ</i> or Invasive Cervical Cancer: A Prospective Population-Based Study
Authors: Laila-Sara Arroyo-Mühr, Camilla Lagheden, Emilie Hultin, Carina Eklund, Hans-Olov Adami, Joakim Dillner, Karin Sundström
Journal: Cancer Research (2019)

The human papillomavirus (HPV) rate of evolution is essential for cancer-preventive strategies targeting HPV. We analyzed variability over time in a prospective, population-based nested case-control study of in situ (CIS) and invasive squamous cervical cancer (SCC). Among 757,690 women who participated in cervical screening in Sweden during 1969 to 2002, we identified 94 women who had HPV16 persistence in two serial cervical screening samples (median 24 months apart, range 0.5-178 months) and later were diagnosed with CIS (n = 59), SCC (n = 32), or remained healthy (n = 3). Whole-HPV16-genome sequencing and comparison of sequences in the serial samples revealed that all women had the same HPV16 lineage, particularly lineage A, in both serial smears. Fifty-six percent of women had an identical 7,906 base pair HPV16 sequence in both samples, and no woman had more than 15 nucleotide substitutions. The median substitution rate was 0 substitutions/site/year (95% confidence interval, 0-0.00008), with no variation between quartiles of follow-up. We concluded that in most women with HPV16 persistence preceding disease, the nucleotide substitution rate was not measurable within up to 15-years follow-up. This slow rate of evolution has important implications for both HPV-based screening and HPV vaccination. SIGNIFICANCE: These findings show there is no genomic variation over time in HPV16 infections progressing to cervical cancer, which could influence risk stratification of women when screening for cervical cancer and inform HPV vaccination strategies.
Isolation of Candida auris from cystic fibrosis patient, Greece, April 2019
Authors: Angeliki Stathi, Ioanna Loukou, Helen Kirikou, Argyri Petrocheilou, Maria Moustaki, Aristea Velegraki, Levantia Zachariadou
Journal: Eurosurveillance (2019)

We report the first isolation of Candida auris in Greece from a sputum culture of a cystic fibrosis patient in their 20s under posaconazole treatment. The pathogen was identified as C. duobushaemulonii by VITEK2YST, but as C. auris by MALDI-TOF MS . This case underscores the need for species-level identification of all non- albicans Candida (NAC) isolates from cystic fibrosis patients and patients with predisposing factors to fungal infection.