tbuckley/cabot-search huggingface dataset:
Efficacy and safety of intrapericardial bleomycin for malignant pericardial effusion.
Authors: I. Moya, E. Dalmau, M. Seguí, Y. García, T. Bonfill, C. Pericay, L. Fernández, R. Querol, M. Pampols, E. Saigí
Journal: Journal of Clinical Oncology (2010)

e19687 Background: Malignant pericardial effusion (MPE) is a relatively common complication of advanced malignancies including lung and breast cancer. Although pericardial drainage results in good palliation of symptoms, it is often inadequate to prevent recurrence of effusion. Intrapericardial (IP) sclerotherapy is associated to good results in terms of recurrence prevention. Absence of MPE at 30 days (d) after sclerosis can be observed in 70 to 90% of treated patients (pts). In comparison to tetracyclines and other agents used for IP sclerosis, bleomycin appears to be effective and safe. Methods: We retrospectively reviewed 18 pts with MPE who had been treated with IP bleomycin at our institution from July 2004 to July 2009. Our aim was to identify the number of MPE recurrences at 30 d and treatment-related morbidity. Results: Twelve men and 6 women with a median age of 62 years were included with diagnosis of lung cancer (67%), breast cancer (11%) and others (22%). They all presented clinical and/or radiological evidence of pericardial effusion. Cytology of the effusion was positive in 8 cases out of the 17 examined (47%). There were no deaths due to initial sclerosis failure or complication of procedure. MPE recurrence developed in 4 pts (22.2%), 3 of which (75%) did so after 30 d. Mild fever (37-37.5°C) occurred in 5 pts (27.8%). Three pts (16.7%) developed atrial fibrillation with rapid ventricular response reverting to sinus rhythm after intravenous administration of amiodarone. Retrosternal pain and infection of catheter were observed in one pt (5.5%). Conclusions: Our experience with MPE is consistent with that reported in literature, supporting the use of bleomycin as IP sclerosing agent to prevent the recurrence of MPE with generally controllable morbidity. No significant financial relationships to disclose.
Abstract 16349: A Novel Class of Inhibitors That Are Specific to Human NPP1 Prevent Pathologic Mineralization of Valve Interstitial Cells
Authors: Elnur E Shayhidin, Elsa Forcellini, Marie-Chloé Boulanger, Mahmut Ablajan, Sébastien Dautrey, Xavier Barbeau, Patrick Lague, Jean Sévigny, Jean-François Paquin, Patrick Mathieu
Journal: Circulation (2014)
Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome
Authors: Marc A. Pfeffer, Brian Claggett, Rafael Diaz, Kenneth Dickstein, Hertzel C. Gerstein, Lars V. Køber, Francesca C. Lawson, Lin Ping, Xiaodan Wei, Eldrin F. Lewis, Aldo P. Maggioni, John J.V. McMurray, Jeffrey L. Probstfield, Matthew C. Riddle, Scott D. Solomon, Jean-Claude Tardif
Journal: New England Journal of Medicine (2015)

Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1-receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event.We randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina.The 6068 patients who underwent randomization were followed for a median of 25 months. A primary end-point event occurred in 406 patients (13.4%) in the lixisenatide group and in 399 (13.2%) in the placebo group (hazard ratio, 1.02; 95% confidence interval [CI], 0.89 to 1.17), which showed the noninferiority of lixisenatide to placebo (P<0.001) but did not show superiority (P=0.81). There were no significant between-group differences in the rate of hospitalization for heart failure (hazard ratio in the lixisenatide group, 0.96; 95% CI, 0.75 to 1.23) or the rate of death (hazard ratio, 0.94; 95% CI, 0.78 to 1.13). Lixisenatide was not associated with a higher rate of serious adverse events or severe hypoglycemia, pancreatitis, pancreatic neoplasms, or allergic reactions than was placebo.In patients with type 2 diabetes and a recent acute coronary syndrome, the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events. (Funded by Sanofi; ELIXA ClinicalTrials.gov number, NCT01147250.).
Government slow to improve services for people with learning disabilities, report finds
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The government should establish a new national commissioner to promote and protect the rights of people with learning disabilities and autism in England, a new report has said.1

Stephen Bubb, chief executive of the Association of Chief Executives of Voluntary Organisations, has been reviewing services since the BBC’s Panorama investigative journalism programme showed abuse at the private Winterbourne View Hospital near Bristol in 2011. He said that progress had been too slow since the scandal.2

Bubb, who was asked by NHS …
Transformation to SCLC after Treatment with the ALK Inhibitor Alectinib
Authors: Shiro Fujita, Katsuhiro Masago, Nobuyuki Katakami, Yasushi Yatabe
Journal: Journal of Thoracic Oncology (2016)

We report an anaplastic lymphoma receptor tyrosine kinase gene (ALK)-positive patient who showed a paradoxical response to the ALK inhibitor alectinib; the primary lesion increased in size, whereas other metastatic lesions decreased markedly. A biopsy of the primary lesion confirmed an ALK rearrangement; however, the tumor had transformed histologically into small cell lung cancer. The lack of reports of small cell lung cancer transformation in ALK-positive patients implies that this outcome was unusual; this patient was treated with alectinib, which is more selective and has a greater inhibitory effect than crizotinib. This case may reveal resistance mechanisms that differ according to the agent used for treatment.
GW26-e1583 N-epsilon-(carboxymethyl)lysine is associated with cardiac diastolic dysfunction in alloxan-induced type 1 diabetic rabbits with early diabetic cardiomyopathy
Authors: Ruimin Dong, Leile Tang, Xujing Xie, Zhenda Zheng, Yanting Luo, Jieming Zhu, Jinlai Liu, Lin Chen
Journal: Journal of the American College of Cardiology (2015)
Postmastectomy radiation for stage ll breast cancer patients with T1/T2 lesions.
Authors: Shai Libson, Charles Ma, Cristiane Takita, Eli Avisar
Journal: Journal of Clinical Oncology (2012)

175 Background: Post mastectomy radiation (PMR) is usually recommended for T3 or N2 breast cancer (BC). The role of PMR for stage ll BC with T1/T2 lesions remains controversial. The aim of this study was to assess the role of PMR in this subgroup of patients. Methods: A retrospective analysis of a prospectively collected database of all stage ll BC patients treated with mastectomy at our institution between 2005-2008 was performed. Demographics, tumor stage, histology, receptor status, adjuvant therapy, nodal status, failure patterns and disease free survival rates (DFS) were compared between the patients who received PMR vs.those who were not radiated. Results: Eighty-two patients underwent mastectomies for stage II disease with a T1/T2 lesion. Twenty two of those (27%) received PMR. The average follow up time was 47 months. The patients in the PMR group had significantly larger tumors (90% vs. 64%), more advanced stages (55% vs. 17%) and higher grade histology (59% vs. 32%). Menopausal status, nodal disease, histology, multifocality and receptors status did not differ significantly between the groups. Three patients in the non radiated (NR) group had a distant recurrence compared to 2 patients in the PMR group. There was one contra-lateral cancer in the NR group. The overall DFS was 86.6% in the NR group vs.91% in the PMR group, (p=0.72). Four patients had a chest wall recurrence (CWR) in the non-radiated (NR) group compared to none in the PMR group; however this was not statistically significant. In a sub-groups analysis comparing only T2, Stage IIB and high grade tumors respectively between the PMR and NR groups there was also no statistical difference in local or distant recurrence and in DFS. In the NR group, high grade tumors (p=0.0024) and estrogen receptors (ER) negativity (p=0.0168) were prognosticators of CWR. Conclusions: In our series PMR did not result in a statistically improved outcome for stage ll BC with T1/T2 lesions. A prospective trial randomizing patients with high grade or ER negative tumors only between PMR vs. NR could further clarify the role of PMR for stage II (T1/T2) lesions.
Use of a genome-wide association study to detect candidate polymorphisms associated with overall survival in stage IV pancreatic adenocarcinoma patients receiving gemcitabine monotherapy
Authors: H. Ueno, T. Okusaka, J. Furuse, H. Ishii, N. Saijo, Y. Saito, J. Sawada, H. Sakamoto, T. Yoshida, Y. Sato
Journal: Journal of Clinical Oncology (2009)

4611 Background: Individual variations in overall survival time (OS) or antitumor effects may be partly explained by host genetic factors, which have not yet been identified. We performed a genome-wide association study (GWAS) in Japanese patients with stage IV pancreatic adenocarcinoma receiving gemcitabine (Gem) monotherapy. Methods: Metastatic pancreatic ductal adenocarcinoma patients who had previously received neither radiation nor chemotherapy were eligible in this study. Gem was administered as a 30-min i.v. infusion at either 800 or 1000 mg/m 2 . The peripheral blood leukocyte DNA samples were genotyped at 110,000 SNPs using Illuimina's Human-1 Genotyping BeadChip. Statistical analyses were performed by the log-rank test and Cox proportional hazards model in consideration of linkage disequilibrium. Results: From Jul 2002 to Jul 2006, 67 patients (male/female: 44/23, PS 0/1/2: 31/32/4, 36–78 (median: 62) years of age were enrolled. The median survival time (MST) of these 67 patients was 5.8 months. In the GWAS, we detected 11 candidate SNPs which were associated with significantly shortened OS. Eventually, 6 SNPs were MAF&gt;5% and remained statistically significant even after multiple comparison adjustment: rs1861674 in the LOH12CR1 gene (MST for CC [n=60] and CT [n=7] + TT [n=0] were 6.4 and 1.6 months, respectively; P=1.0×10 -7 , HR=8.25 (3.3–20.9)), rs10504551 in the TCEB1 (MST for CT [n=28] + CC [n=36] and TT [n=3] were 5.8 and 1.0 months. P=1.1×10 -7 , HR=14.9 (3.9–56.1)), rs1132750 (MST for AC [n=18] + AA [n=45] and CC [n=4] were 6.3 and 1.1 months. P=4.6×10 -11 , HR=23.5 (6.1–91.7)), rs2055943 in the GABRA4 (MST for AC [n=27] + CC [n=36] and AA [n=4] were 6.3 and 1.2 months. 1.3×10 -11 , HR=26.1 (6.4–107), rs2589506 in the MAPK10 (MST for AG [n=29] + GG [n=31] and AA [n=7] were 6.4 and 1.1 months. P=3.2×10 -6 , HR=5.9 (2.6–14.1)) and rs2586404 in the DNM3 (MST for CT [n=30] + CC [n=33] and TT [n=3] were 5.8 and 0.62 months. P=3.4×10 -9 , HR=18.6 (4.9–71.5)). Conclusions: GWAS is a powerful tool to search for new prognostic biomarkers for patients with stage IV pancreatic adenocarcinoma receiving Gem monotherapy and may reveal as yet unexplored molecular pathways which correlate with drug response. [Table: see text]
Agreement between physicians and patients about what constitutes shared decision making
Authors: C. A. Charles, P. M. Ellis, S. J. Dimitry, M. A. O’Brien, T. J. Whelan
Journal: Journal of Clinical Oncology (2006)

6065 Background: Involving patients in making decisions about their own care is increasingly desirable for patients with serious illness. Shared decision making is one such model, the attributes of which have been well defined (Charles et al., Soc Sci Med,1997,1999). However, it is unclear whether physicians and patients agree on what constitutes a SDM interaction. Methods: Semi-structured interviews were undertaken with 21 medical and radiation oncologists and 14 cancer patients attending a regional cancer centre. Participants were asked what they thought it meant for the patient and physician to share in DM. Responses were compared to the theoretical constructs of SDM defined by Charles et al: information exchange (flow, direction, type, amount), deliberation, and who makes the decision. Two analysts independently reviewed the interviews for patient and physician definitions of SDM and compared these with the Charles et al. model of SDM using explicit classification decision rules. There were few discrepancies between analysts and agreement was reached in all cases. Results: 71% of physicians and 29% of patients described a two-way flow and direction of information exchange as necessary for SDM. Only 24% of physicians and 21% of patients described the exchange of both medical and personal information. All participants indicated that more than the minimum legally required amount of information was needed. 67% of physicians and 36% of patients described both patient and physician involvement in deliberation about treatment as a component of SDM. 48% of physicians and 21% of patients identified both patients and physicians are involved in deciding what treatment to implement in a shared approach. Overall, none of the participant definitions identified all the components of the SDM model. Physicians in their definitions, identified more components than did patients. Conclusions: Physicians appear to have a stronger understanding of the elements involved in SDM. These differences may lead to different expectations about patient involvement in DM. Physicians have a responsibility for ensuring that patients are invited to contribute to all components of SDM in the oncology consultation. No significant financial relationships to disclose.
Resistance Against Staphyloccus aureus
Authors: Stuart Mudd
Journal: JAMA (1971)

Protection against the invasiveness of<i>Staphylococcus aureus</i>has been sought for many decades through use of staphylococcal vaccines. The assumption has been that circulating antibodies could be called up to promote phagocytosis and killing of<i>Staph aureus</i>, in analogy with the effects of antibodies against streptococci and pneumococci. Results have been disappointing, for the reason that the underlying assumption is not true. Explanation lies in the peculiar immunochemistry of the surface of the staphylococcal cell. Fortunately, however, the special attributes of<i>Staph aureus</i>do offer promise in the guise of cell-mediated resistance. A high proportion of human subjects are colonized or infected with<i>Staph aureus</i>and, in consequence, have allergy, characterized by delayed-type hypersensitivity to<i>Staph aureus</i>. Cell-mediated resistance can be elicited by appropriate administration of staphylococcal antigens; such antigens are licensed and in use.
The Addition of the BTK Inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma
Authors: Marco Ruella, Saad S. Kenderian, Olga Shestova, Joseph A. Fraietta, Sohail Qayyum, Qian Zhang, Marcela V. Maus, Xiaobin Liu, Selene Nunez-Cruz, Michael Klichinsky, Omkar U. Kawalekar, Michael Milone, Simon F. Lacey, Anthony Mato, Stephen J. Schuster, Michael Kalos, Carl H. June, Saar Gill, Mariusz A. Wasik
Journal: Clinical Cancer Research (2016)

Responses to therapy with chimeric antigen receptor T cells recognizing CD19 (CART19, CTL019) may vary by histology. Mantle cell lymphoma (MCL) represents a B-cell malignancy that remains incurable despite novel therapies such as the BTK inhibitor ibrutinib, and where data from CTL019 therapy are scant. Using MCL as a model, we sought to build upon the outcomes from CTL019 and from ibrutinib therapy by combining these in a rational manner.
The Liberty to Die
Authors: Ryan P. Clodfelter, Eli Y. Adashi
Journal: JAMA (2016)

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Factors affecting long-term outcomes after postchemotherapy surgery in patients with nonseminomatous germ cell tumors of the mediastinum.
Authors: E. Fadel, B. de Latour, K. Fizazi, J. P. Droz, P. Dartevelle
Journal: Journal of Clinical Oncology (2010)

e15019 Background: To identify factors that affect long-term survival after postchemotherapy resection of residual disease in patients with nonseminomatous germ cell tumors arising from the mediastinum (NSGCTM). Methods: Between 1983 and 2009, 52 patients (49 males and 3 females) with NSGCTM underwent surgical resection of postchemotherapy residual disease in our institution. Serum tumor markers (STM) were elevated in 49 patients at diagnosis and remained increased preoperatively in 14 of them despite a second line chemotherapy. Uni and multivariate analyses were performed. Results: A complete resection was achieved in 49 patients with on histology viable germ cell tumor in 23 patients, sarcoma in 3, only teratoma in 10 and only necrosis in 16 patients. Postoperatively, STM level was normal in 44 patients. Adjuvant chemotherapy was given to 20 patients. Two patients died postoperatively and 20 other patients died during follow-up (14 from tumor recurrence, 5 from leukaemia and one from pulmonary fibrosis). The 5-year survival rate was 57% and was significantly worse in patients with elevated preoperative STM (34% vs 65%, p=0.03), viable tumor on residual disease ( 39% vs 75%, p=0.01), and in patients incomplete resection (0% vs 61%, p=0.02). By multivariate analysis, only viable tumor significantly affected survival (p=0.04). Conclusions: Patients with NSGCTM can be cured by an aggressive postchemotherapy residual disease resection. Conversely to viable residual tumor on pathologic findings, elevated preoperative STM was not found to be an independent factor of lower survival and thus should not preclude surgical resection. No significant financial relationships to disclose.
Effect of taxanes following anthracyclines on pathologic complete response (pCR) in patients with triple-negative breast cancer (TNBC) receiving primary systemic therapy (PST).
Authors: S. Gildetti, C. Natoli, M. Zilli, A. Grassadonia, N. Tinari, M. Scognamiglio, J. Giampietro, D. Angelucci, E. Cianchetti, S. Iacobelli
Journal: Journal of Clinical Oncology (2010)

e13129 Background: TNBC is an aggressive molecular subtype associated with increased risk of distant metastases and poor prognosis. In this study we report response to PST and clinical outcome of a cohort of patients with TNBC. Methods: We retrospectively evaluated 217 patients with nonmetastatic breast cancer receiving PST between March 1999 and July 2009. TNBC was defined as hormone receptors (HR) and human epidermal growth receptor-2 (HER-2) negative at immunohistochemistry. Treatment consisted of anthracycline regimens alone (FEC/EC; 88 patients) or followed by taxanes (129 patients). Nineteen out of 63 HER2-positive patients received trastuzumab in combination with taxanes. Primary endpoint was pCR, defined as absence of invasive cancer both in breast and axillary lymph nodes at surgery. Secondary endpoint was disease free-survival (DFS) evaluated by the Kaplan-Meier method. Results: Thirty-nine out of 217 patients (18%) were TNBC. Among 178 non-TNBC, 115 (53%) were HR positive/HER-2 negative, 31 (14%) were HR negative/HER-2 positive and 32 (15%) were HR positive/HER-2 positive. Patients with TNBC had a trend to a higher pCR rate compared with non-TNBC (15.4% vs. 12.4%, p=0.06). Tumor response according to the PST regimen is shown in the Table. A significantly higher pCR rate to anthracyclines followed by taxanes was observed in non-TNBC (18.2% vs. 2.9%, p<0.02), but not in TNBC (15% vs. 15.8%, p=n.s.). At a median follow-up of 40 months, patients with TNBC showed a shorter DFS compared to non-TNBC (p<0.01). Conclusions: In TNBC, the use of anthracyclines followed by taxanes is not superior to anthracyclines alone. TNBC patients were more likely to respond to PST, but had a worse DFS with respect to non-TNBC patients. Anthracyclines Anthracyclines followed by taxanes TNBC non-TNBC TNBC non-TNBC Patients (N) 20 68 19 110 pCR 3 (15%) 2 (2.9%) 3 (15.8%) 20 (18.2%) No significant financial relationships to disclose.
Immuno-chemotherapy of advanced colorectal cancer with alpha-2a interferon and 5-fluorouracil. Immunopharmacological studies
Authors: R. De Filippi, G. Cucchiara, S.P. Prete, S. Marini, F. Ricci, C. Nunziata, M. Turriziani, E. Bonmassar, M.P. Fuggetta, L. De Vecchis
Journal: Annals of Oncology (1991)
Humanized Anti-HM1.24 Antibody Mediates Myeloma Cell Cytotoxicity That Is Enhanced by Cytokine Stimulation of Effector Cells
Authors: Shuji Ozaki, Masaaki Kosaka, Yuji Wakahara, Yasuko Ozaki, Masayuki Tsuchiya, Yasuo Koishihara, Tetsuya Goto, Toshio Matsumoto
Journal: Blood (1999)
Are disease management programs for COPD cost-effective?
Authors: M Boland, A Tsiachristas, A Kruis, N Chavannes, M Rutten-van Molken
Journal: European Respiratory Journal (2012)

Background  There is insufficient evidence of cost-effectiveness of COPD disease management (COPD-DM) programs.  Aim  The aim of this study is to review the impact of COPD-DM on healthcare costs and outcomes. We also investigated the impact of disease-, intervention-, and study-characteristics.  Methods  We conducted a systematic review to identify cost-effectiveness of COPD-DM. The data, results, and characteristics of the studies were grouped and, if feasible, included in a random-effects meta-analysis.  Results  We included 16 papers describing 11 studies. The meta-analysis showed that DM decrease hospitalizations (RR: 0.76 [95CI: 0.63-0.93]), and let to a significant reduction of hospitalization costs (€1196 [95CI: €722 -€1670]) per patient per year (PPPY). Average healthcare savings were €1914 [95CI: €1464-€2365] PPPY. These savings have to be weighed against the costs of developing, implementing and managing the DM program. Our results showed great variability in disease-, intervention-, and study-characteristics. There are indications that DM showed greater savings in hospital costs in studies with: severe COPD patients (GOLD stage 3+), patients with exacerbations, smokers, non-RCT design, short intervention duration, low methodological quality, 1-2 Chronic Care Model components and non-EU origin.  Conclusion  DM decreased the risk of hospitalization and healthcare costs (excluding program costs). Furthermore, cost-effectiveness was influenced by heterogeneity in study-, intervention-, and disease-characteristics. Although favourable results on healthcare costs and effects have been demonstrated, more studies are needed to draw conclusions on the impact of DM on total costs and cost-effectiveness of DM in different settings.