tbuckley/cabot-search huggingface dataset:
Comparing COPD care in Malta, to other European hospitals: Results from the ERS COPD audit
Authors: Eleanor Gerada, Josephine Bigeni, Cynthia Farrugia Jones
Journal: European Respiratory Journal (2012)

Background:  Proper management of COPD can reduce exacerbations, which in turn reduces disease-related mortality.   Aim:  To find out how management of COPD exacerbations in Malta contrasts with other countries.   Methods:  A total of 422 European hospitals took part. Every COPD patient admitted with an exacerbation to our hospital over 8 weeks, was included (n=112). The ERS COPD audit proforma and web tool was used. Data was processed by the Data Analysis Team. The authors take full responsibility for any inferences made in this abstract.   Results:  The median length of stay was 5 days, while the European Median (EM) was 8 days; there is no early supported discharge programme locally (31.8% of European hospitals run this). The 90-day readmission rate was 47.6% locally vs. 35.1% EM. In Malta there is no respiratory ward (81.7% EM), no specialist COPD clinic (61.8% EM), nor respiratory nurse specialists. There are 4 respiratory teams and 46.4% of patients were seen by pulmonologists (EM 80%). On admission, only 48.2% had spirometry results available (59.6% EM). 6.4% needed NIV (13.4% EM), but 91.1% of patients improved before NIV was needed (40% EM). On discharge 15.5% were given LTOT (30.4% EM), the PaO2 our patients had on admission was 66.9mmHg vs. 59.4mmHg EM. 49.1% of our cases satisfied GOLD criteria to be discharged on LAMA (1.8% vs. 59.8% EM) or ICS + LABA (12.5% vs. 69.5% EM). 45.5% of patients were on antibiotics on discharge (11.9% EM). The 90-day mortality was 7.6% (6.1% EM). Still, this was COPD-related in only 37.5%.   Conclusions:  In Malta management of COPD needs to be optimised by establishing and adhering to guidelines. Specialised care is recommended as well as re-auditing at a later stage.
Abstract 13555: Synergism of PDE3 and PDE4 Activity Regulates cAMP-Mediated PKA-Dependent Local Ca2+ Releases to Modulate Basal Spontaneous Firing of Cardiac Pacemaker Cells
Authors: Tatiana M Vinogradova, Alexey E Lyashkov, Yue Li, Yevgeniya Lukyanenko, Edward G Lakatta
Journal: Circulation (2012)

The spontaneous beating rate of rabbit sinoatrial node cells (SANC) is controlled by cAMP-mediated, PKA-dependent (cAMP/PKA) local subsarcolemmal Ca2+ releases (LCRs) from ryanodine receptors (RyR)...
Relation of in vitro colony survival to clinical response in a prospective trial of single-agent chemotherapy for metastatic melanoma.
Authors: F L Meyskens, L Loescher, T E Moon, B Takasugi, S E Salmon
Journal: Journal of Clinical Oncology (1984)

We have used the effect of therapeutic agents on clonogenic growth in agar to discriminate between active and inactive agents for malignant melanoma. We report a prospective study of single-agent chemotherapy for metastatic melanoma. Forty-five separate in vitro/in vivo correlative trials were conducted in 34 patients. A number of agents were used in these evaluations, including actinomycin D, Amsacrine, bisantrene, mitoxantrone, BCNU, vinblastine, vindesine, 5-fluorouracil, MGBG, etoposide, interferon, tamoxifen, and 13-cis-retinoic acid. At the "cut-off" concentration, a colony survival less than 30% was designated as "sensitivity" and greater than 30% as "resistance." Clinical sensitivity was designated to include complete, partial, and mixed responses and was predicted in eight of 18 trials (44%). Clinical resistance (nonresponse) was predicted correctly in 24 of 27 cases (89%). Using Fisher's exact test the association of in vitro and in vivo results was significant (P = .05). These results offer further support for the concept that clonogenic assays may help select useful agents for clinical trials in metastatic melanoma.
Is clamping of chest tubes for air leak necessary
Authors: Vasileios Kouritas, Charalampos Zissis, Bellenis Ion
Journal: European Respiratory Journal (2013)

OBJECTIVE: Occult air leak, not observed clinically, may lead to the recurrence of pneumothorax. Many clinicians prefer to clamp the chest tube before removal. Aim of the present study is to investigate the need for clamping of the chest tube before removal.

PATIENTS AND METHODS: Surgical patients, spontaneous pneumothorax (SP) and traumatic pneumothorax patients after cessation of air leak were randomly categorized into a clamp and no-clamp chest tube removal group. The analyzed variables included; the demographic data, the chest tube drainage duration, the number and size of recurrences of pneumothorax, the needed interventions, the in-hospital stay, the morbidity and mortality. Significance was tested with student’s t-test, Mann-Whitney and χ2 test. p <0.05 was accepted as significant.

RESULTS: Overall 120 patients (72.5% males, mean age 52.1 years) were included in the study. In the clamp group, relapses of pneumothorax tended to be lesser (p=0.075), the mean size of pneumothorax was smaller (p=0.042) and eventually fewer interventions were needed (p=0.042). Fifteen cases regarded SP patients, whereas 9 regarded cancer and 9 trauma patients (p=0.06). In SP no-clamp group, relapses were more (p=0.028), with a greater mean pneumothorax size (p=0.05) and more intereventions eventually needed (p=0.048, more new chest tubes inserted than in other groups p=0.038) with longer in-hospital stay (p=0.048) when compared to the clamp group. No differences were calculated in the elective surgery and trauma groups.

CONCLUSIONS: The chest tube for pneumothorax should be clamped before removal in SP cases. Otherwise, the pneumothorax tends to relapse with greater size, more interventions are needed and in-hospital stay is prolonged.
Do American oncologists know how to use prognostic variables for patients with newly diagnosed primary breast cancer?
Authors: C L Loprinzi, P M Ravdin, M de Laurentiis, P Novotny
Journal: Journal of Clinical Oncology (1994)

PURPOSE This project was designed to investigate how American medical oncologists actually use prognostic information to treat primary breast cancer patients, and to study their difficulties in combining complex and sometimes contradictory information. METHODS A simple 2-page questionnaire was faxed in May and June 1993 to a sample of American medical oncologists who were members of the American Society of Clinical Oncology (ASCO). RESULTS When presented with simple case histories of patients with newly diagnosed invasive breast cancer and asked to assess prognosis on the basis of tumor size, number of involved axillary nodes, patient age, estrogen receptor level, and progesterone receptor level, there was a wide divergence of opinions about the probability of disease-free survival at 10 years (both for cases in which the patient received no adjuvant therapy and for those in which the patient did receive such therapy). The use of additional prognostic data (such as S-phase, tumor histologic and nuclear grading, and cathepsin D status) did not refine the estimates, but led to an equal or greater dispersion of estimates of prognosis. CONCLUSION There is a clear need for tools to help oncologists integrate prognostic information for primary breast cancer patients. Such tools might lead to greater accuracy and uniformity of prognostic estimates. Such tools might also help make clear what prognostic tests are worth using for routine clinical practice.
Lack of Carcinogenic Activity of 3-Methylcholanthrene in the Squirrel Monkey&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D Steinmuller, L A Dillingham, R T Prehn
Journal: JNCI Journal of the National Cancer Institute (1969)

The carcinogenic activity of 3-methylcholanthrene (MCA) was tested in the squirrel monkey, Saimiri sciureus. Discs of 5% MCA-impregnated paraffin were implanted subcutaneously in 5 adult squirrel monkeys. These discs produce fibrosarcomas in murine recipients in 3–6 months. To provide the same systemic exposure as well as local concentration of carcinogen as in a 25 g mouse, the monkeys were given 1 disc/25 g body weight or 21–26 discs each. Pieces of skin were taken from 3 other monkeys, cut into fine fragments, and returned to their respective donors as 12–16 subcutaneous trocar implants together with crystals of full-strength MCA. In mice, such implants readily give rise to a high incidence of carcinomas. One of the 8 subjects died of a respiratory infection at 42 days and 3 others of various causes about 1½–2 years after MCA application. No tumors or neoplastic changes of any kind were found at autopsy. The 4 others are alive and under observation about 4 years after MCA application, and no tumors have arisen to date. The toxicity of MCA to newborn squirrel monkey cells in vitro was also evaluated. In contrast to the marked toxicity of MCA to normal mouse cells in vitro, no effect was noted on the normal squirrel monkey cells.
Abstract 16302: Early Alterations in Nuclear Ca2+ Handling - Key Role in Heart Failure Progression?
Authors: Senka Ljubojevic, Simon Sedej, Michael Sacherer, Michael Sereinigg, Jens Kockskamper, Burkert Pieske
Journal: Circulation (2012)

Nucleoplasmic Ca concentration ([Ca]nuc) in cardiac myocytes (CMs) modulates transcription and its alteration is involved in remodeling processes. We thus characterized changes of nuclear Ca handli...
Late toxicity after adjuvant radiochemotherapy for gastric adenocarcinoma
Authors: B. Wysocka, Z. Kassam, G. Lockwood, J. Brierley, L. Dawson, J. Ringash
Journal: Journal of Clinical Oncology (2006)

14042 Background: There is limited late toxicity data following adjuvant radiochemotherapy for resected gastric cancer. Methods: We reviewed radiation dose volume histograms (DVHs) and toxicity outcomes for gastric cancer patients (stage Ib to IV) who received adjuvant conformal radiochemotherapy between November 2000 and May 2005. Charts were reviewed to determine survival, late clinical toxicity, and biochemical markers of renal or hepatic toxicity (creatinine, bilirubin, ALP, AST, ALT). DVHs for kidneys and liver were correlated with toxicity outcomes. Overall (OS), disease-free (DFS) and event (death or late toxicity) -free (EFS) survival were calculated. Results: 80 of 88 patients’ DVHs were available for review. Mean age was 58 years (range: 22 - 75), with 53 (66%) males and 27 (34%) females. Stage distribution was: IB - 13 (16%), II - 32 (40%), IIIA - 24 (30%), IIIB - 4 (9%) and IV - 7 (9%). 3D conformal radiotherapy (45 Gy/25 fractions) was used. In 69 patients, chemotherapy was standard as per the INT-116 study; 11 study patients received infusional 5FU (200mg/m 2 /day for 12 weeks) and cisplatin in escalating dose (4 cycles q 2 weeks, 0–30 mg/m 2 ). All treatment was completed in 56 (70%) patients; 9 (11%) did not complete radiotherapy and 22 (27.5%) had chemotherapy dose omissions. Median follow up is 30 months (range 6–62). At 2 years, OS was 84% (95% CI 73%-90%), DFS was 66% (95% CI 53%-75%) and EFS was 61% (95% CI 49–72%). Clinical late toxicity occurred in 6 patients 9 to 53 months following treatment: bowel obstruction/perforation (2) and anastomotic stricture (4), in volumes treated to 45 Gy. No clinical symptoms of renal or hepatic toxicity were reported. Grade 1 (CTCAE v3.0) elevation of creatinine was observed in 8 (10%) patients; at least one liver test was altered in 22 (27.5%) patients, (grade 1–17; 2–4; 3–1). Abnormal bloodwork occurred 9 days to 55 months following treatment and did not correlate with higher kidney and liver doses. Conclusions: In our cohort of patients treated with conformal radiochemotherapy, small bowel and anastomotic toxicity was most common, with no clinical renal or hepatic toxicity observed. Biochemical renal and hepatic changes were not related to clinical toxicity or dose delivered. Further assessment with longer follow-up in a larger sample is planned. No significant financial relationships to disclose.
Abstract 13400: Myopalladin Mutation Induced ERK1/2 and CARP/ANKRD1 Dysregulation in Restrictive Cardiomyopathy
Authors: Uzmee Mendsaikhan, Ruben Martherus, Ken Takagi, Anne-Cecile Huby, Nan Gong, Kristen Kramer, Zaza Khuchua, Jeffrey A Towbin, Enkhsaikhan Purevjav
Journal: Circulation (2013)
Pharmacokinetic and pharmacodynamic evaluation after administration of beclomethasone dipropionate and formoterol fumarate as fixed or free metered-dose inhaler combination in adolescent asthma
Authors: Piotr Kuna, Germano Lucci, Mirco Govoni, Roberta Baronio, Elena Carzana, Anja Elgalal, Iwona Stelmach
Journal: European Respiratory Journal (2013)

INTRODUCTION: Foster pMDI is a fixed dose combination of beclomethasone dipropionate (BDP) 100µg and formoterol fumarate (FF) 6µg marketed for use in adult asthma with or without a spacer device (AeroChamber PlusTM, AC).

OBJECTIVE: To investigate the pharmacokinetic (PK), pharmacodynamic (PD) and safety profile of Foster in asthmatic adolescents with or without AC, in comparison to a free combination of marketed pMDI products: Qvar 100µg for BDP and Atimos 6µg for FF.

METHODS: Open label, randomized, three-way crossover study on 30 asthmatic adolescents receiving a single dose of BDP/FF (400µg/24µg) as Foster, Foster+AC or Qvar+Atimos. All assessments were performed over 8h post-dose.

RESULTS: Foster with or without AC was equivalent to Qvar+Atimos or Foster alone in terms of systemic exposure (AUC0-t) to B17MP (active metabolite of BDP) and FF; 90% CIs for the geometric means ratio fixed/free were within 0.8-1.25. Dose administration with Foster+AC resulted in slightly higher peak concentrations (Cmax) of B17MP and FF than with Qvar+Atimos or Foster alone. Foster with or without AC showed a similar PD (FEV1, plasma potassium and glucose) and safety profile (pulse rate) in comparison to Qvar+Atimos.

CONCLUSIONS: Overall, data show comparable PK, PD and safety profiles of Foster, with or without AC, in comparison to the free combination of marketed BDP+FF in asthmatic adolescents, with only a slight increase in peak plasma concentrations of B17MP and FF when AC is used, in agreement with data already obtained in the adult population.
Reoperation for brain metastases.
Authors: N Sundaresan, V P Sachdev, G V DiGiacinto, J E Hughes
Journal: Journal of Clinical Oncology (1988)

We report the results of reoperation for brain metastases in 21 patients with recurrent tumors following initial successful resection. The tumor recurrences were local (original site) in 14 patients, and occurred at other sites in the brain in the remaining seven. Time to CNS recurrence ranged from 3 to 30 months. At time of repeat craniotomy, disease was limited to the CNS in 12 (57%) of the patients. Median survival following second craniotomy was 9 months, and the actuarial 2-year survival was 25%. Neurological improvement was seen in two thirds of the patients; the median duration of neurological improvement was 6 months. There was no mortality, and only one patient developed increased deficit following surgery. We conclude that repeat resection of brain metastases is an important therapeutic option in selected patients, and should be considered in symptomatic patients with accessible mass lesions before the use of other experimental treatment.
Intermediate-risk prostate cancer: A Medicare-based cost comparison of five radiotherapy regimens.
Authors: Romaine Charles Nichols, Kathy McIntyre, Juana Gifford, Steve K. Ritz, Stuart Klein, Curtis Bryant, Randal H. Henderson, William M. Mendenhall, Nancy Price Mendenhall, Bradford S. Hoppe
Journal: Journal of Clinical Oncology (2015)

108 Background: Patients with intermediate risk prostate cancer choosing radiotherapy may be treated with a number of regimens. The current study compares the direct treatment cost for five therapeutic options based on Fiscal Year 2014 Medicare allowable reimbursements. Methods: Hypothetical charge sheets were generated along with the expected Medicare allowable reimbursements (based on global billing where applicable) for the following regimens: 1.) Image Guided Intensity Modulated Radiotherapy (IGIMRT) to a dose of 78Gy in 39 fractions with one field reduction (IGIMRT); 2.) Dose escalated IGIMRT to 84.60Gy in 47 fractions with one field reduction (MSKCC-IGIMRT); 3.)IGIMRT to a dose of 45Gy in 25 fractions followed by a 90 seed I125 prostate implant (IGIMRT-BTX); 4.) Image Guided Proton Therapy to a dose of 78Gy(RBE) in 39 fractions with one field reduction (SFPT); 5.) Image Guided Hypofractionated Proton Therapy to a dose of 72.50Gy(RBE) in 29 fractions with one field reduction (HFPT). Results: Based on Fiscal Year 2014 Medicare allowable reimbursements, the direct cost for each of these interventions including professional fees, technical fees, isotope costs and facility fees is shown in the Table. Conclusions: This data presents a framework for evaluating the cost effectiveness of proton therapy as compared to competing therapeutic options. Under current Medicare allowable reimbursements, the cost of proton therapy relative to the cost of other therapeutic options is highly dependent on the number of radiotherapy fractions delivered. The feasibility of delivering hypofractionated proton therapy for patients with localized prostate cancer is being investigated at a number of institutions as well as within the framework of a multicenter protocol. Ultimately the cost of proton therapy will need to be weighed against tumor control probabilities as well as the economic and quality of life benefits associated with reduced normal tissue exposure. [Table: see text]
A phase I and pharmacologic study of capecitabine and paclitaxel in breast cancer patients
Authors: M.A. Villalona-Calero, J.L. Blum, S.E. Jones, S. Diab, R. Elledge, P. Khoury, D. Von Hoff, M. Kraynak, J. Moczygemba, P. Kromelis, T. Griffin, E.K. Rowinsky
Journal: Annals of Oncology (2001)
Interpreting out-of-pocket expenditures for cancer patients: The importance of considering baseline household income information
Authors: W. S. Oatis, N. Nonzee, T. Markossian, V. Shankaran, J. McKoy, A. Evens, L. Gordon, J. Winter, E. Calhoun, C. L. Bennett
Journal: Journal of Clinical Oncology (2009)

6541 Background: Few studies have examined cancer-related out-of-pocket costs (expenses resulting from cancer morbidity and treatment that are not covered by insurance) as a function of baseline household income. We report income-adjusted out-of-pocket cost ratios for 50 patients with lymphoma and 156 patients with breast cancer. Methods: Patients with lymphoma or breast cancer provided 3-month retrospective documentation of cancer-related out-of-pocket costs. Costs were adjusted for income by dividing monthly costs by monthly household income. Direct medical costs include costs related to medications, doctor visits, and hospital stays. Direct non-medical costs are cancer-related peripheral costs, such as transportation and meals. Indirect costs are costs due to lost income. Results: Of our study patients, 83% were Caucasian, 65% were married, 53% were employed, and 65% had at least a bachelor's degree. All patients were undergoing active treatment and had insurance. Mean monthly out-of-pocket costs for patients with lymphoma were slightly greater than for those with breast cancer ($1,888 vs $1,455, respectively). Among patients with an annual income of $30,000 or less, the total monthly out-of-pocket costs were more than 3 times the monthly household income for patients with lymphoma and equal to the monthly household income for patients with breast cancer. The total mean income-adjusted cost ratio was 1.75 for patients with aggressive non-Hodgkin lymphoma versus 0.42 and 0.61 for those with indolent non-Hodgkin lymphoma or Hodgkin disease, respectively. Conclusions: Cancer-related out-of-pocket expenses disproportionately affect lower-income individuals with lymphoma or breast cancer and are primarily driven by the financial burden of co-payments for medical care. Future studies should evaluate out-of-pocket costs in relation to household income to determine more accurately the economic burden of cancer. [Table: see text] No significant financial relationships to disclose.
BACH: A randomized phase II trial of doxorubicin-cyclophosphamide (AC) versus pegylated liposomal doxorubicin (PLD)-cyclophosphamide-trastuzumab (CCH) followed by paclitaxel-trastuzumab (TH) as adjuvant therapy for HER2-positive breast cancer (BC)—Cardiac safety analysis.
Authors: D. Rayson, T. Suter, S. van der Vegt, A. Lluch, J. Van Den Bosch, G. Lopez-Vivanco, A. M. Van Gent, H. Wildiers, L. Provencher, D. Richel
Journal: Journal of Clinical Oncology (2010)

559 Background: For patients (pts) with HER2+ BC, concurrent AC-H results in unacceptable cardiotoxicity rates. Substituting PLD for A in an adjuvant regimen may minimize cardiotoxic risk and permit earlier integration of adjuvant H. Methods: Inthis randomized phase II trial, pts with resected lymph node+ or high-risk, node-negative HER2+ BC were stratified by age and randomized (1:2) to: Arm A: AC (60/600 mg/m2 q21d × 4) followed by T 80 mg/m2 + H 2 mg/kg qwk × 12 or Arm B: PLD 35 mg/m2 + C 600 mg/m2 q21d × 4 + H 2 mg/kg/wk × 12, followed by T 80 mg/m2 + H 2 mg/kg qwk × 12. Subsequent H for a total of 1y was given as per institutional standards. Primary objective was incidence of level 1 (cardiac death or severe heart failure with left ventricular ejection fraction [LVEF] drop > 10% to < 50%) and level 2 (asymptomatic/mild heart failure with LVEF drop > 10% to < 50%) cardiac event rates during the 8 cycles of chemotherapy (CT). This analysis reports cardiotoxicity for the entire patient population completing 8 cycles of CT. Results: 181 pts were randomized between 8/2007 and 4/2009; 59 in Arm A and 118 in Arm B were eligible for cardiac toxicity assessment (modified ITT). Median age was 52.5 y (Arm A; range 30-71) and 50.1 y (Arm B; range 20-83); 98.3% in Arm A and 100% in Arm B had ECOG PS 0-1. No level 1 cardiotoxic events were observed in either arm. Three level 2 cardiotoxic events occurred in Arm A (5.1%; 95% CI: 1.1-14.1) and 1 event in Arm B (0.8%; 95% CI: 0.0-4.6). The mean LVEF reduction from baseline to completion of CT in Arm A was 5.3% (SD 6.38), vs. 2.2% (SD 6.25) in Arm B (p = 0.0015). 16.7% of pts in Arm B vs. 11.9% in Arm A experienced a serious adverse event (AE). Grade 3-4 AEs included (Arm A vs. B) alopecia (8.5 vs. 1.7%), PPE (0 vs. 15%), fatigue (0 vs. 1.7%), rash (0 vs. 4.2%), mucositis (0 vs. 2.5%), nausea (3.4 vs. 0%), and febrile neutropenia (6.8 vs. 4.1%). Conclusions: Concurrent CCH followed by TH as adjuvant therapy for HER2+ BC appears to be safe from a cardiac standpoint and did not increase cardiac event rates compared to AC-TH. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline, Roche Roche, sanofi-aventis, Schering-Plough Roche, University Hospital Leuven
Tyrosine kinase inhibitor–induced CD70 expression mediates drug resistance in leukemia stem cells by activating Wnt signaling
Authors: Carsten Riether, Christian M. Schürch, Christoph Flury, Magdalena Hinterbrandner, Linda Drück, Anne-Laure Huguenin, Gabriela M. Baerlocher, Ramin Radpour, Adrian F. Ochsenbein
Journal: Science Translational Medicine (2015)

CD70 expression induced by tyrosine kinase inhibitors mediates drug resistance in leukemia stem cells.
A Network Monitoring Program to Improve Safety and Management in Ambulatory Chemotherapy Unit
Authors: F. Scotte, R. Elaidi, C. Thibault, H. Aboudagga, C. Gervais, M. Kfoury, B. Bonan, J. Stevens, V. Tual, P. Leroy, S. Oudard
Journal: Annals of Oncology (2014)