tbuckley/cabot-search huggingface dataset:
Prevalence of pulmonary arterial hypertension and right ventricular dysfunction in COPD patients in the Kirov region of Russia
Authors: Julia Chuyasova, Vasiliy Pyankov, Elena Poyarkova
Journal: European Respiratory Journal (2011)

Purpose: To estimate the prevalence of pulmonary artery hypertension (PAH) and right ventricular (RV) dysfunction in COPD patients in the Kirov region of Russia.

Material and methods: 1088 COPD patients (mean age 55±14 years, 97% men and 3% women) were studied. All the patients underwent physical examination, laboratory investigations and transthoracic echocardiography. RV end-diastolic diameter, RV wall thickness and right atrium (RA) area were measured. The systolic pulmonary arterial pressure (PAP) was measured by pulsed Doppler (systolic PAP = tricuspid regurgitation pressure gradient + estimated RA pressure). RA pressure was estimated based on the diameter and respiratory variation of the inferior vena cava. Mean PAP was calculated with formula: mean PAP = 0.61×PA systolic pressure + 2 mm Hg. Global RV systolic function was estimated using RV myocardial performance index and RV fractional area change. RV diastolic function was assessed using transtricuspid E/A ratio and E/E' ratio.

Results: PAH (systolic PAP > 37 mmHg and mean PAP > 25 mmHg) was detected in 40.3% of cases (438 patients). Right ventricular (RV) remodeling and dysfunction were revealed in all COPD patients with PAH. Diastolic RV dysfunction was detected in 100% and systolic RV dysfunction - in 12.8% of those cases (56 patients).

Conclusions: Our study confirmed high prevalence of PAH and RV dysfunction in COPD patients in the Kirov region of Russia. Prognosis of these patients is characterized by an increased risk of death. Physicians should detect PAH in COPD patients as early as possible and start treatment for prevention complications.
Junior doctors’ dispute goes beyond pay, Tory MP says
Authors: Gareth Iacobucci
Journal: BMJ (2015)

The UK government’s threat to impose a new contract on junior doctors could have “unintended consequences” for the NHS if increasing numbers of skilled staff decide to leave the profession as a result, the chair of the House of Commons Health Committee has warned.

Sarah Wollaston, the former GP turned Conservative MP who leads the parliamentary select committee, also said that junior doctors’ grievances went “beyond pay” and were about staff feeling valued.

Speaking at a fringe session at the Conservative Party’s annual conference in Manchester on Monday 5 October, Wollaston told delegates that her own insight into the …
Impact of presence of cancer emboli in blood vessels around tumor on survival of young patients with breast cancer
Authors: A. Gevorgyan, N. Chobanyan, A. Nersesyan
Journal: Journal of Clinical Oncology (2005)

725 Background: Survival of young patients with breast cancer is poor. Although, research shows negative influence of a significant number of pathological factors on survival of breast cancer patients, there is no clear impact of presence of cancer emboli in blood vessels around tumor on survival of patients with premenopausal breast cancer, especially young patients with breast cancer.The aim of this study is to determine the impact of presence of cancer emboli in blood vessels around tumor on survival of young patients compared with middle age group. Material and method Study involves 2 groups of patients with stages II-III of premenopausal breast cancer. 375 patients were young age (20–35 years old), and 380 -middle age (36–45 y.o).Cancer emboli in blood vessels around tumor were analyzed on surgical specimens after mastectomy. 5 and 10- year survival was established by “ life table” Method: Comparative analysis of 5- and 10- year survival rates done under influence of presence or absence of cancer emboli in blood vessels around tumor in patients of young and middle age. Results: Within young age group presence of cancer emboli in blood vessels around tumor statistically decrease survival rate of patients compared with cases of absence of cancer emboli:5 and 10-year survival rates were:37,9+ 6,2%, 25,1±6,7% and 70,6±2,2%, 57,4±3,0%, respectively (p<0,05). Comparative analysis of survival rates in presence of cancer emboli in blood vessels around tumor between age groups showed statistically significant decrease of survival rate in the young patients: 5 and 10-year survival rates were 37,9+ 6,2%, 25,1±6,7% and 59,8±3,2%, 51,3±2,2%, respectively (p<0,05). Conclusion: Presence of cancer emboli in blood vessels around tumor showed statistically significant negative influence on survival of young patients with breast cancer compared with middle age group.Differences in survival rate of two age groups within premenopausal breast cancer may be reflection of the existence of basic differences of immune-endocrine relationships in patients young and middle age groups. No significant financial relationships to disclose.
Use of deep whole transcriptome sequencing in Philadelphia-positive acute lymphoblastic leukemia (ALL) to identify novel mutated genes and aberrant gene expression and alternative splicing profiles associated with disease progression.
Authors: I. Iacobucci, A. Ferrarini, M. Sazzini, A. Lonetti, E. Giacomelli, L. Xumerle, A. Ferrari, C. Papayannidis, M. Delledonne, G. Martinelli
Journal: Journal of Clinical Oncology (2010)

6546 Background: Although the pathogenesis of BCR-ABL1+ ALL is mainly related to the expression of BCR-ABL1, additional genetic lesions are supposed to be involved. Methods: In order to define the full repertoire of leukemia-related mutations, changes in expression profiles and alternative splicing (AS) events, we used a Whole Transcriptome Sequencing (Illumina/Solexa) approach to sequence the leukemia transcriptome of BCR-ABL1+ ALL cases at diagnosis and relapse. Results: This analysis generated 13.9 and 15.8 million reads from de novo and relapsed samples, respectively, detecting transcripts from 62% and 64% of human annotated genes. Reads that showed no match to the human genome reference sequence (UCSC hg18) were mapped to a dataset of all possible splice junctions created in silico and 4,334 and 3,651 primary and relapse AS were identified. The well-known alternatively spliced Ik6 of the IKZF1 gene was also detected. Finally, 2,011 and 2,103 single nucleotide variants (SNVs) were found at diagnosis and relapse respectively, about 94% of which have been already reported in the dbSNP. As potential ALL-related mutations, 124 and 114 not annotated SNVs were found at diagnosis and relapse, respectively. Of these, 43 affected both samples, while 81 and 71 resulted private variants. 12 nonsynonymous changes were found on the coding sequences of annotated genes: 1 affecting PLXNB2 on both samples, 6 affecting genes involved in metabolic processes (PDE4DIP, EIF2S3, DPEP1, ZC3H12D, TMEM46) and transport (MVP) at diagnosis and 3 affecting genes involved in cell cycle regulation (CDC2L1) and catalytic activity (CTSZ, CXorf21) at relapse. The T315I mutation in the Bcr-Abl kinase domain was also identified. All these mutations were validated by deep exon sequencing in an additional subset of 24 ALL patients and correlated with prognosis. Conclusions: Our findings demonstrated for the first time in BCR-ABL1+ positive ALL that deep sequencing is a suitable approach for identifying a wide spectrum of genetic alterations. Supported by: AIL, AIRC, FIRB 2006, European LeukemiaNet. No significant financial relationships to disclose.
Resource utilization, costs, and quality of end-of-life cancer care: A systematic review of retrospective cohort studies based on routinely collected data (1990-2011).
Authors: Julia M. Langton, Bianca Blanch, Annabelle Drew, Marion Haas, Jane M. Ingham, Sallie Pearson
Journal: Journal of Clinical Oncology (2013)

111 Background: The last year of life is one of the most resource intensive periods in cancer care. The aim of this systematic review is to synthesize retrospective observational studies examining resource utilization and costs at the end-of-life period in adult cancer patients. The purpose is to examine study methodology and outcomes, with a particular focus on studies using quality indicators. Methods: We searched Medline, Embase, CINAHL, and York Centre for Research and Dissemination (1990-2011). Two reviewers screened titles and abstracts of 14,424 articles and 835 full-text, potentially relevant articles. Inclusion criteria were: English-language; at least one resource utilization or cost outcome in adult cancer decedents with solid tumors; outcomes derived from health administrative data; and an exclusive end-of-life or palliative focus. Results: We reviewed 78 studies examining end-of-life care in over 3.7 million cancer decedents; 55 were from the North America; and 33 published since 2008. We observed exponential increases in service use and costs as death approached. Hospital services were the main cost driver. Palliative services were relatively underutilized, and associated with lower expenditures than hospital-based care. The 15 studies using quality of care indicators demonstrated significant proportions of up to 33% of patients receive chemotherapy or life sustaining treatments in the last month of life; up to 66% do not receive hospice/palliative services. Conclusions: Observational studies using routinely collected health administrative data have the potential to drive evidence-based palliative care practice and policy. Further refinement of quality of care markers will enhance benchmarking activities across health care jurisdictions, providers, and patient populations.
Indeterminate pulmonary nodules in breast cancer: Clinical significance and management
Authors: B. Lee, A. Lim, R. C. Leonard, J. Lewis, C. R. Coombes, J. Stebbing
Journal: Journal of Clinical Oncology (2008)

617 Background: Increasing numbers of patients with early breast cancer undergo routine staging using computerized tomography (CT). Those in whom indeterminate pulmonary nodules are visualized without the presence of other potentially metastatic lesions represent a clinical dilemma of whether they should be managed as early breast cancer or metastatic disease. This study sought to investigate the incidence, clinical characteristics and outcomes of patients with indeterminate pulmonary nodules in breast cancer, which has important implications for their management and also entry into clinical trials. Methods: Medical records of individual breast cancer patients who underwent thoracic CT scans between the years 2002 to 2007 were analyzed and those with obvious metastatic disease were excluded. Patients were identified via the radiology database by searching for the following terms: suspicious lung metastases, and/ or indeterminate nodules. Results: Out of 2,578 patients scans, we identified 34 cases (1.3%) with indeterminate pulmonary nodules without evidence of disease elsewhere on CT scanning. We categorized these cases to the size of the nodules. At a median follow-up of 13.5 months, there were no changes in lesion size in 86% of the patients with a solitary nodule smaller than 1cm, and 89% with multiple sub-centimeter nodules. In contrast, 100% of cases with pulmonary nodules larger than 1cm had progressed at follow up (χ2, p=0.004). Conclusions: Breast cancer cases with sub-centimeter indeterminate pulmonary lesions and no evidence of metastases elsewhere are unlikely to represent metastatic disease. Treatment with curative intent or entry into clinical trials should not be excluded. No significant financial relationships to disclose.
Retrospective study of impact of race and health care insurance on stage at presentation of common cancer at a rural university hospital over a 10 years period—1996 to 2005
Authors: N. C. D’Cunha, M. Chiriva Internati, E. Cobos, S. Sugathadasa
Journal: Journal of Clinical Oncology (2008)

17537 Background: Minorities tend to seek treatment when their cancer is in more advanced stage. This retrospective study is to see the impact of race and health care insurance on stage at presentation of common cancer at a rural university hospital Methods: Data from patients with breast, lung, colorectal and head neck cancer, treated from 1996 to 2005 at a rural university hospital were collected from the cancer registry data bank. Breast, colorectal, lung, and head/neck cancer were chosen because of increase frequency of these cancers, and also early diagnosis of these cancers could lead to cure. Patients were analyzed for their ethnicity, insurance type, and stage of cancer at diagnosis. Cancer stages 0 to 2 were considered early stage where as cancer stage 3 to 4 were considered late stage. Health care insurances were classified as not insured, private insurance, medicaid, medicare and unknown. The null hypothesis and the alternative hypothesis were used for statistical analysis. The chi square test for independence using a contingency table was performed. Results: Of the 1698 patients studied, 551 had breast cancer, 609 had lung cancer, 377 had colorectal cancer and 161 had head/neck cancer. 525 patients with breast cancer, 609 with lung cancer, 347 patients with colorectal and 148 patients with head/neck cancer could be analyzed. At a significance level of 0.05, we can conclude that for breast cancer the type of insurance patient had and the stage of cancer at presentation are related. This was not true for lung cancer, colorectal cancer, and head/neck cancer. With regards to relationship between type of insurance and ethnic type at a significance level of 0.05, type of insurance patients had and ethnic type are related only for breast cancer and lung cancer and not for head/neck cancer. For colorectal cancer the type of insurance patients have and ethnic type were related only at a significance level of 0.1. Conclusion: Minority patients like Hispanics and African Americans having breast and lung cancer are more likely to have no insurance and hence present at a later stage. Future focus should be on these individual for early detection of cancer especially breast and lung cancer which are curable at an early stage. No significant financial relationships to disclose.
Docetaxel plus carboplatin (DC) may have significant activity in hormone refractory prostate cancer (HRPC) patients who have progressed after prior docetaxel-based chemotherapy
Authors: M. H. Tay, D. J. George, T. D. Gilligan, S. M. Kelly, L. Appleby, M.-E. Taplin, P. G. Febbo, P. W. Kantoff, W. K. Oh
Journal: Journal of Clinical Oncology (2004)

4679 Background: Chemotherapy is now increasingly used in HRPC management. The two most frequently used regimens are mitoxantrone-prednisone (MP) and docetaxel-estramustine (DE) beyond which options are limited. One of the potential reasons for disease progression in HRPC is increased neuroendocrine differentiation of the disease. Although carboplatin, a drug active in neuroendocrinally differentiated tumor, has modest activity in HRPC as a single agent, we retrospectively report 3 of the 4 patients consecutively treated and responded with salvage docetaxel-carboplatin (DC) following failure to docetaxel-based chemotherapy. Methods: 4 patients with metastatic HRPC who had failed docetaxel based chemotherapy and at least one line of chemotherapy were treated with docetaxel at 60–70 mg/m2 and carboplatin at AUC 4 given 3 weekly. Patients were monitored for measurable PSA response and toxicity. Results: 3 of the 4 patients had > 50% PSA decrease, together with improvement of performance status, weight gain and decrease pain medication. Median age of 4 patients was 73 years old. Prior treatments include D alone in patient 1, MP, epothilone analogue and DE in patient 2 and DE with bevacizumab in patient 3. The mean PSA decrease was 74% (97%, 75% and 50% respectively). The durations of PSA response were 20, 10 and 32 weeks respectively. Overall survival was 20 weeks and 63 weeks for patients 2 and 3 while patient 1 is still alive at 36 weeks of follow-up. Fatigue was the main toxicity and docetaxel dose reduction from 60 to 50 mg/m2 was required for one while another patient was switched to weekly docetaxel schedule. There were no grade 3 or 4 hematologic toxicities. Conclusions: Docetaxel-refractory HRPC may still respond to DC, though carboplatin by itself has modest activity. The significant response seen in these 3 patients suggest a possible synergistic effect of the two drugs. A prospective phase II trial of DC for HRPC patients who had failed prior chemotherapies which included docetaxel (but not a platinum) has been initiated. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Bristol-Myers Squibb
Costs and benefits of adjuvant therapy in breast cancer: a quality-adjusted survival analysis.
Authors: A Goldhirsch, R D Gelber, R J Simes, P Glasziou, A S Coates
Journal: Journal of Clinical Oncology (1989)

The use of adjuvant chemotherapy for postmenopausal patients with early breast cancer remains controversial because the potential benefits in terms of prolongation of disease-free survival (DFS) and overall survival (OS) must be balanced against the toxicity of treatment. Following mastectomy, 463 evaluable postmenopausal women with node-positive breast cancer were randomized to receive either chemoendocrine therapy for 1 year, or endocrine therapy alone for 1 year, or no adjuvant therapy (Ludwig Trial III). At 7-years median follow-up, OS was longer for the chemoendocrine-treated patients compared with controls (P = .04) and compared with the adjuvant endocrine therapy-alone group (P = .08). In order to balance this therapeutic advantage against the toxic effects of treatment, OS time was divided into time with toxicity (TOX), time without symptoms and toxicity (TWiST), and time after systemic relapse (REL). TOX and REL were weighted by coefficients of utility relative to TWiST and the results added to give a period of quality-adjusted survival (Q-TWiST). Benefits measured by Q-TWiST generally favored chemoendocrine therapy. For example, if TOX and REL were both given utility coefficients of 0.5 relative to 1.0 for TWiST, then by 7 years the average Q-TWiST for chemoendocrine therapy was 6.7 months longer than for no-adjuvant therapy (P = .05) and 4.1 months longer than for endocrine therapy alone (P = .20). Quality-adjusted survival analysis is recommended in assessing costs and benefits of toxic adjuvant therapy. In this example, it supports the use of chemoendocrine therapy in postmenopausal node-positive patients for a wide range of relative values assigned to periods with symptoms and toxicity.
Rates of central nervous system progression in non-small cell lung cancer patients treated with EGFR-TKI’s vs. chemotherapy
Authors: M. S. Rabin, L. Cioffredi, B. Y. Yeap, R. A. Williams, B. E. Johnson, D. M. Jackman
Journal: Journal of Clinical Oncology (2008)

8059 Background: Case reports have shown that EGFR-TKI’s can be effective against brain mets from NSCLC. It is unclear, however, what effect these agents might have on the rate and time to occurrence of CNS mets or progression. Methods: We conducted a comprehensive review of our institution’s patient database to identify those pts who had been treated for NSCLC between 5/01 and 8/07. All pts provided informed consent to be included in the database. To isolate the effect of the role of EGFR-TKI’s, pts who had received a first-line EGFR-TKI were compared with those who received chemotherapy alone and never received a subsequent EGFR-TKI. Focus was given to those pts who achieved evidence of systemic benefit (had a TTP of ≥ 3 months) from the start of 1st-line therapy. The cumulative actuarial risk of CNS progression was based on the estimated cumulative incidence function, considering death due to other causes as a competing risk. Results: A total of 352 pts had received an EGFR-TKI as 1st line therapy for advanced NSCLC; of those, 105 remained on therapy ≥ 3 months. A total of 137 pts received cytotoxic chemo as 1st line therapy without ever receiving subsequent EGFR-TKI; of these, 78 had a TTP of ≥ 3 months. Demographics (see table). Among the total of 93 pts still alive, the median follow-up is 12 months. The cumulative actuarial risk of CNS metastasis/progression for the EGFR-TKI group was 6% at one year and 17% at two years, while the respective risks for the chemo group were 27% and 33% (p=0.001). For chemo pts with pre-existing brain mets, risk of subsequent CNS progression was 44% at both 12 and 18 months; for EGFR-TKI pts, 12-mo risk was 9% but increased to 45% by 18 mo (p=0.501). Conclusions: Compared with chemo, pts who achieve systemic benefit from treatment with an EGFR-TKI appear to have a lower rate of CNS progression. The incidence of progression of pre-existing brain disease was not significantly affected by the type of systemic therapy administered, albeit based on small patient numbers. Baseline pt characteristics and results EGFR-TKI group Chemo group % female 72 56 median age (yrs) 70 64 Smoking, never/current/former (%) 32/62/5 15/77/6 Histology, adeno/SCC/LCC/NSCLC NOS 82/3/2/13 63/14/1/22 Prior Brain Mets (%) 10 21 Cumulative risk of CNS progression, 1 yr (%) 6 27 Cumulative risk of CNS progression, 2 yrs (%) 17 33 SCC=squamous cell carcinoma; LCC = large cell carcinoma; NOS= not otherwise specified. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech, Genzyme Genentech, Roche Genzyme
Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity
Authors: Mylène M Maury, Yu-Huan Tsai, Caroline Charlier, Marie Touchon, Viviane Chenal-Francisque, Alexandre Leclercq, Alexis Criscuolo, Charlotte Gaultier, Sophie Roussel, Anne Brisabois, Olivier Disson, Eduardo P C Rocha, Sylvain Brisse, Marc Lecuit
Journal: Nature Genetics (2016)
Randomized trial of adjuvant chemotherapy with mitomycin plus ftorafur versus mitomycin alone in resected locally advanced gastric cancer.
Authors: J J Grau, J Estapé, J Fuster, X Filella, J Visa, J Terés, G Soler, S Albiol, J C García-Valdecasas, L Grande, J Bombí, J Bordas, F Alcobendas
Journal: Journal of Clinical Oncology (1998)

PURPOSE We performed a clinical trial to determine whether postoperative adjuvant chemotherapy with two drugs versus one drug could prolong survival. PATIENTS AND METHODS From 1985 to 1996, 85 patients with completely resected locally advanced gastric cancer were enrolled. The subjects were randomized into two treatment groups, as follows: mitomycin (MMC) 10 to 20 mg/m2 intravenously (i.v.) on day 1 every 6 weeks plus ftorafur (FT) 500 mg/m2/d for 36 consecutive days; or MMC alone, 10 to 20 mg/m2 i.v. every 6 weeks. All courses were repeated four times. RESULTS After a median follow-up duration of 62 months, the overall 5-year survival rates were 67% for the MMC-FT group versus 44% for the MMC group (P = .04). Subgroup analysis to compare survival curves using the method of Mantel-Cox showed survival rates significantly in favor of the MMC-FT group in the subsets of patients with node-negative disease (P = .01) and those whose disease was stage IB or II (P = .008). CONCLUSION Significantly better survival results were observed for MMC-FT versus MMC alone. Subset analysis suggest a strong benefit in patients with node-negative and early-stage resected gastric cancer.