tbuckley/cabot-search huggingface dataset:
P18.04 * CLINICAL PROGRESS AND SURVIVAL OF PATIENTS WITH GLIOBLASTOMA AFTER HYPO-FRACTIONATED RADIOTHERAPY
Authors: A. D. Jakes, M. Boyer, P. Hatfield
Journal: Neuro-Oncology (2014)

INTRODUCTION: The standard adjuvant treatment in fit patients with glioblastoma multiforme is chemo-radiotherapy. However, this may be inappropriate in older patients, or those with a low Karnofsky Performance Score (KPS). Hypo-fractionated radiotherapy (30 Gy in 6 fractions over 2 weeks) is an alternative approach for this group. Nevertheless, the prognosis remains poor, so early palliative care input and effective communication between secondary and primary care is essential. This study was designed to assess whether the palliative intent of treatment and prognosis were being discussed and documented adequately. The clinical progress and treatment of patients post-radiotherapy was also determined. METHODS: Patients were identified who had been diagnosed with glioblastoma multiforme, between the years 2006-2013, and subsequently treated with hypo-fractionated radiotherapy in Leeds. Patient demographic data, performance status, date of tissue diagnosis and death, if applicable, were recorded. Surgical procedures and chemotherapy were also noted. Initial clinic letters after diagnosis were used to assess communication with patients and their general practitioners. RESULTS: A total of 114 patients were identified. The majority of patients were male (78; 68%) and of white British origin (110; 96%). The median age at diagnosis was 64 (Min 29, Max 83) years. Median survival was 6.8 (IQR: 4.4-10.0) months from date of diagnosis, with 19 (16%) surviving to 1-year. All but one patient received a tissue diagnosis, with 85 (73%) patients receiving debulking surgery. The survival difference between those who had debulking surgery and biopsy was 7.2 (5.1-11.3) and 6.1 (3.9-8.4) respectively (p = 0.108). Median time between tissue diagnosis and radiotherapy was 34 (27-42) days. 17 (15%) patients subsequently received palliative chemotherapy. The palliative intent of treatment was communicated to the patient and GP in 93 (82%) initial clinic letters. Prognosis was discussed and documented in 45 (39%) consultations, but only 23 (20%) communicated this to the GP. Resuscitation status was never documented. Performance score was recorded in 73 (64%) initial letters. The palliative nature of the treatment was reiterated to 70 patients, however only 15 had prognosis documented. Twenty-five (22%) patients did not attend a post-radiotherapy clinic, with a further 25 (22%) not returning after their first post-radiotherapy visit. At the last attended clinic before a patient's death, 57 (50%) patients had a further clinic appointment booked. CONCLUSION: We found that nearly a quarter of patients never returned to clinic after their radiotherapy and nearly a half only returned once. Ensuring the patient and GP are aware of the possible prognosis and palliative intent of treatment is essential to allow adequate end-of-life care planning.
Engineering Cell‐Compatible Paper Chips for Cell Culturing, Drug Screening, and Mass Spectrometric Sensing
Authors: Qiushui Chen, Ziyi He, Wu Liu, Xuexia Lin, Jing Wu, Haifang Li, Jin‐Ming Lin
Journal: Advanced Healthcare Materials (2015)

Paper‐supported cell culture is an unprecedented development for advanced bioassays. This study reports a strategy for in vitro engineering of cell‐compatible paper chips that allow for adherent cell culture, quantitative assessment of drug efficiency, and label‐free sensing of intracellular molecules via paper spray mass spectrometry. The polycarbonate paper is employed as an excellent alternative bioscaffold for cell distribution, adhesion, and growth, as well as allowing for fluorescence imaging without light scattering. The cell‐cultured paper chips are thus amenable to fabricate 3D tissue construction and cocultures by flexible deformation, stacks and assembly by layers of cells. As a result, the successful development of cell‐compatible paper chips subsequently offers a uniquely flexible approach for in situ sensing of live cell components by paper spray mass spectrometry, allowing profiling the cellular lipids and quantitative measurement of drug metabolism with minimum sample pretreatment. Consequently, the developed paper chips for adherent cell culture are inexpensive for one‐time use, compatible with high throughputs, and amenable to label‐free and rapid analysis.
American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors As Adjuvant Therapy for Postmenopausal Women With Hormone Receptor–Positive Breast Cancer: Status Report 2004
Authors: Eric P. Winer, Clifford Hudis, Harold J. Burstein, Antonio C. Wolff, Kathleen I. Pritchard, James N. Ingle, Rowan T. Chlebowski, Richard Gelber, Stephan B. Edge, Julie Gralow, Melody A. Cobleigh, Eleftherios P. Mamounas, Lori J. Goldstein, Timothy J. Whelan, Trevor J. Powles, John Bryant, Cheryl Perkins, Judy Perotti, Susan Braun, Amy S. Langer, George P. Browman, Mark R. Somerfield
Journal: Journal of Clinical Oncology (2004)

To update the 2003 American Society of Clinical Oncology technology assessment on adjuvant use of aromatase inhibitors.Based on results from multiple large randomized trials, adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer should include an aromatase inhibitor in order to lower the risk of tumor recurrence. Neither the optimal timing nor duration of aromatase inhibitor therapy is established. Aromatase inhibitors are appropriate as initial treatment for women with contraindications to tamoxifen. For all other postmenopausal women, treatment options include 5 years of aromatase inhibitors treatment or sequential therapy consisting of tamoxifen (for either 2 to 3 years or 5 years) followed by aromatase inhibitors for 2 to 3, or 5 years. Patients intolerant of aromatase inhibitors should receive tamoxifen. There are no data on the use of tamoxifen after an aromatase inhibitor in the adjuvant setting. Women with hormone receptor-negative tumors should not receive adjuvant endocrine therapy. The role of other biomarkers such as progesterone receptor and HER2 status in selecting optimal endocrine therapy remains controversial. Aromatase inhibitors are contraindicated in premenopausal women; there are limited data concerning their role in women with treatment-related amenorrhea. The side effect profiles of tamoxifen and aromatase inhibitors differ. The late consequences of aromatase inhibitor therapy, including osteoporosis, are not well characterized.The Panel believes that optimal adjuvant hormonal therapy for a postmenopausal woman with receptor-positive breast cancer includes an aromatase inhibitor as initial therapy or after treatment with tamoxifen. Women with breast cancer and their physicians must weigh the risks and benefits of all therapeutic options.
Hydrodynamic Forces in Dissecting Aneurysms
Authors: EDWARD K. PROKOP, ROGER F. PALMER, MYRON W. WHEAT
Journal: Circulation Research (1970)

It has been argued that pulse wave characteristics are important factors in extension and rupture of acute dissecting aneurysms. To test this, a standard model of an aorta was constructed, consisting of an outer layer of Tygon tubing and an inner layer of rubber cement. An "intimal tear" was produced and the "aorta" was subjected to nonpulsatile and pulsatile flow with increasing increments of pressure. With nonpulsatile flow alone (97 experiments) no dissection occurred at pressures up to 400 mm Hg. Pulsatile flow produced rapid and usually complete dissection with a maximum systolic pressure of 120 mm Hg. The extent of dissection per pulse was related to dp/dt max in the fluid. No dissection occurred until a critical value of dp/dt max (790 mm Hg/sec) was reached. Dog aortas were then used in place of the Tygon tube "aorta" with similar results; i.e., dissection did not occur with nonpulsatile flow, but did occur with pulsatile flow (3800 mm Hg/sec). The dissecting dog aorta ruptured to the outside or reentered the vessel lumen. It was concluded that pulse wave characteristics, particularly dp/dt max , are important in the propagation of dissection.
SSRI Use During Pregnancy and Risk of Stillbirth and Neonatal Mortality
Authors: Espen Jimenez-Solem, Jon Trærup Andersen, Morten Petersen, Kasper Broedbaek, Anders Rune Lander, Shoaib Afzal, Christian Torp-Pedersen, Henrik E. Poulsen
Journal: American Journal of Psychiatry (2013)

Objective The authors investigated whether in utero exposure to selective serotonin reuptake inhibitors (SSRIs) increases the risk of stillbirth or neonatal mortality. Method The authors conducted a population-based cohort study using the Danish Fertility Database to identify every birth in Denmark between 1995 and 2008. Time of exposure to SSRIs was calculated on the basis of standard treatment dosages and dispensed pack sizes according to the prescription register. Exposure was divided into first-, second-, and third-trimester exposure. Multivariate logistic regression models were used. Results The authors identified 920,620 births; the incidence of stillbirths was 0.45%, and the incidence of neonatal mortality was 0.34%. A total of 12,425 offspring were exposed to an SSRI during pregnancy. Stillbirth was not associated with first-trimester SSRI use (adjusted odds ratio=0.77, 95% CI=0.43–1.36), first- and second-trimester use (odds ratio=0.84, 95% CI=0.40–1.77), or first-, second-, and third-trimester use (odds ratio=1.06, 95% CI=0.71–1.58). Neonatal mortality was not associated with SSRI first-trimester use (odds ratio=0.56, 95% CI=0.25–1.24), first- and second-trimester use (odds ratio=0.90, 95% CI=0.37–2.17), or first-, second-, and third-trimester use (odds ratio=1.27, 95% CI=0.82–1.99). Conclusions This study found no association between exposure to SSRIs during pregnancy and stillbirth or neonatal mortality.
Urokinase-mediated fibrinolysis in the synovial fluid of rheumatoid arthritis patients may be affected by the inactivation of single chain urokinase type plasminogen activator by thrombin
Authors: E A M Braat
Journal: Annals of the Rheumatic Diseases (2000)

Excessive fibrin deposition within the inflamed joints of rheumatoid arthritis (RA) patients suggests that local fibrinolysis is inefficient, which seems to be in contrast with the observed increased levels of urokinase type plasminogen activator (u-PA). Thrombin-mediated inactivation of single chain u-PA (scu-PA) into an inactive form called thrombin-cleaved two chain u-PA (tcu-PA/T) may provide a possible explanation for this contradiction.To assess the occurrence of tcu-PA/T in the synovial fluid of patients with RA and with osteoarthritis (OA), and in the synovial fluid of controls to find support for thrombin-mediated inactivation of scu-PA in RA.Levels of scu-PA and tcu-PA/T were measured in the synovial fluid of 20 RA patients, nine OA patients and 14 controls using sensitive bioimmunoassays. Total urokinase antigen was quantified by a urokinase ELISA.tcu-PA/T was found in the synovial fluid of all RA and OA patients. Only in seven of 14 control samples, levels of tcu-PA/T could be measured above the detection limit of the assay (0.2 ng/ml). The concentrations of tcu-PA/T, scu-PA and u-PA:Ag were significantly higher in the synovial fluid of the RA and OA patients as compared with the controls, while the RA patients had significantly higher levels of tcu-PA/T and u-PA:Ag than the OA patients. In RA, tcu-PA/T seemed to account for more than 40% of total urokinase antigen, while the contribution of tcu-PA/T to total urokinase antigen was only minor in OA and the controls (9.0% and 6.6%, respectively).A significant part of the high total urokinase antigen in the synovial fluid of RA patients can be attributed to tcu-PA/T, implying that a large amount of scu-PA is not available for fibrinolysis because of its inactivation by thrombin. Thus, thrombin may promote the inflammation process in RA by inhibiting the fibrinolytic system and preventing the removal of fibrin.
Approach to Patients With Pancreatic Cancer Without Detectable Metastases
Authors: Gregory M. Heestand, James D. Murphy, Andrew M. Lowy
Journal: Journal of Clinical Oncology (2015)

The poors outcomes associated with pancreatic cancer clearly reflect the advanced stage of disease at diagnosis for most patients. Through this lens, it is easy to lose sight of the fact that roughly 50% of patients with pancreatic cancer have no clinically detectable metastases at presentation. Herein, we discuss how patients with localized pancreatic cancer are currently managed. The primary goal of care for patients with resectable and borderline-resectable tumors is cure, facilitated by achieving margin-negative resection of the primary disease and delivering effective adjuvant and/or neoadjuvant therapy. For patients with locally advanced disease, the focus is on limiting local progression and outgrowth of metastatic disease and maintaining quality of life. Although it was once a centerpiece of therapy for localized pancreatic cancer, the value and place of radiation therapy in the treatment algorithm is now under increased scrutiny. In contrast, given its value as demonstrated in multiple prospective trials, chemotherapy is an established part of the treatment paradigm for all patients. With the demonstration that cytotoxic combinations such as fluorouracil, leucovorin, irinotecan, and oxaliplatin as well as gemcitabine/nab-paclitaxel are active in the metastatic setting, these agents are now being studied in patients with localized disease. The neoadjuvant setting provides a particularly favorable setting for evaluating new systemic strategies. Given the array of new targets, including immunomodulatory approaches, there is reason for optimism that we can markedly improve survival for all patients with pancreatic cancer and enter an era in which surgery with curative intent actually fulfills this goal on a much more regular basis.
Respiratory mechanics in airways obstruction associated with inspiratory dyspnoea.
Authors: J M O'Connell, A H Campbell
Journal: Thorax (1976)

Inspiratory muscle strength and the flow and elastic pressure opposing inspiration were measured in seven patients with severe airways obstruction who found inspiration difficult at rest. A comparison was made of measurements obtained from seven normal subjects and five patients with airways obstruction not experiencing inspiratory dyspnoea at rest. Measurements were also obtained when inspiratory dyspnoea was induced in the normal subjects by adding an inspiratory resistance or by voluntarily increasing lung volume. Compared with the controls the inspiratory muscle strength of the patients was reduced but was not significantly less than that of the patients without inspiratory dyspnoea. The pressure required to produce inspiratory flow was significantly greater when inspiratory dyspnoea was present (P = 0-01). However, there was considerable overlap in the pressures of those with and without inspiratory dyspnoea. A better relationship was obtained when muscle strength was considered. The ratio of inspiratory muscle strength to the pressure required to produce flow was 0-24 +/- 0-07 (mean +/- SD) in patient with inspiratory dyspnoea, 0-10 +/- 0-03 in patients without inspiratory dyspnoea, and 0-033 +/- 0-019 in normal subjects. There was no overlap between the two patient groups. The ratios of the normal subjects were increased when inspiratory dyspnoea was induced and, with the exception of two cases, were all above those obtained when inspiratory dyspnoea was absent. Inspiratory dyspnoea was experienced with lower ratios in the normals than in the patients with airways obstruction.
A complex role for the progesterone receptor in the response to vascular injury
Authors: Richard H. Karas, Martin van Eickels, John P. Lydon, Sean Roddy, Moon Kwoun, Mark Aronovitz, Wendy E. Baur, Orla Conneely, Bert W. O’Malley, Michael E. Mendelsohn
Journal: Journal of Clinical Investigation (2001)

Clinical studies of hormone replacement therapy to prevent cardiovascular diseases have heightened interest in the cardiovascular effects of progestins. However, the role of the progesterone receptor (PR) in vascular biology has not been studied in vivo. We studied ovariectomized female PR knockout (PRKO) mice and their wild-type (WT) littermates using the mouse carotid artery injury model. Placebo-treated PRKO mice showed significantly greater vascular medial hypertrophy and vascular smooth muscle cell (VSMC) proliferation in response to vascular injury than did WT mice. Progesterone had no significant effect in the PRKO mice, but worsened the response to injury in WT mice. VSMCs cultured from PRKO mouse aortae were markedly hyperproliferative, and their growth was not affected by progesterone. In contrast to the in vivo findings, progesterone inhibited proliferation of WT-derived VSMCs. Furthermore, reintroduction of PR into PRKO-derived VSMCs using adenoviral methods restored progesterone-mediated inhibition of proliferation to these cells. This effect was reversed by the PR antagonist, RU 486. Thus, the effects of PR and progesterone differ markedly between cultured VSMCs and intact blood vessels. These data demonstrate a direct role for the PR in regulating the response to vascular injury and VSMC proliferation.
Early Cardiac Resynchronization Therapy and Reverse Remodeling in Patients With Mild Heart Failure
Authors: Gary S. Francis, W.H. Wilson Tang
Journal: Circulation (2009)

C ardiac resynchronization therapy (CRT) has been shown to consistently improve cardiac performance and exercise capacity, leading to reversal of cardiac remodeling and improvement in survival in patients with advanced heart failure and a significant ventricular conduction delay.The strategy of CRT for the treatment of advanced heart failure was secured in 2005 by the landmark Cardiac Resynchronization in Heart Failure (CARE-HF) study. 1 Recently, 2 studies have extended these observed benefits of CRT to patients with less advanced (New York Heart Association [NYHA] class I/II) signs and symptoms who still fulfilled standard indications for resynchronization therapy.The recently published Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study demonstrated 34% relative risk reduction in death or heart failure events with CRT and defibrillator (CRT-D) compared with implantable cardioverterdefibrillator alone in 1820 subjects with left ventricular (LV) ejection fraction Յ30% and QRS duration Ն130 ms, which was largely driven by reduction in heart failure events and associated with reverse remodeling. 2 Although the primary end point of a heart failure clinical composite response was not met in the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trial, observed improvement in the prospectively powered secondary end point of LV end-systolic volume index in the presence of CRT suggests that early implementation of CRTϮD in 610 patients with mild heart failure (NYHA class I/II, LV ejection fraction Յ40% and LV end-diastolic dimension Ն55 mm by echocardiography, QRS duration Ն120 ms) may be considered a beneficial strategy. 3The article by St John Sutton and colleagues 4 extends the concept of reverse remodeling of CRT by carefully examining the time course of reverse remodeling and identifying the subgroups that may have a particularly favorable response.The investigators now provide a more expansive analysis of the remodeling data, which is internally consistent and highly favorable.The authors go on to conclude that progressive LV remodeling can be prevented or even reversed by CRT in patients with mild heart failure with the use of resynchronization criteria to the same extent as in those with advanced heart failure, particularly in those with nonischemic etiology.
Symptom severity in advanced cancer, assessed in two ethnic groups by interviews with bereaved family members and friends
Authors: J. Koffman, I. J Higginson, N. Donaldson
Journal: Journal of the Royal Society of Medicine (2003)

Little research has been reported on the experience of cancer among minority ethnic communities in the UK. As part of a wider survey in inner London we interviewed bereaved family members or close friends of 34 first-generation black Caribbeans and of 35 UK-born white patients about symptoms and symptom control in the year before death with cancer. They were drawn from population samples in which the response rates were equal at about 46%. Symptoms in the two ethnic groups were similar. However, multivariate logistic regression indicated greater symptom-related distress in black Caribbeans for appetite loss, pain, dry mouth, vomiting and nausea, and mental confusion. Respondents were also more likely to say, in relation to black Caribbean patients, that general practitioners (though not hospital doctors) could have tried harder to manage symptoms. The findings suggest a need for better assessment and management of cancer symptoms in first-generation Caribbean Londoners, guided by a deeper understanding of cultural influences on their responses to advanced illness.
T-Cell/Histiocyte-Rich Large B-Cell Lymphomas and Classical Diffuse Large B-Cell Lymphomas Have Similar Outcome After Chemotherapy: A Matched-Control Analysis
Authors: R. Bouabdallah, N. Mounier, C. Guettier, T. Molina, V. Ribrag, C. Thieblemont, A. Sonet, A. Delmer, K. Belhadj, P. Gaulard, C. Gisselbrecht, L. Xerri
Journal: Journal of Clinical Oncology (2003)

Because it is unclear whether T-cell/histiocyte-rich large B-cell lymphomas (H/TCRBCL) should be considered as a true clinicopathologic entity, we conducted a matched-control analysis comparing patients with H/TCRBCL and patients with diffuse large-B cell lymphoma (B-DLCL).More than 4,500 patients were enrolled onto non-Hodgkin's lymphoma trials conducted by the Groupe d'Etude des Lymphomes de l'Adulte. After histologic review, 50 patients were subclassified as H/TCRBCL. They were matched to 150 patients with B-DLCL for each of the factors of the International Prognostic Index (IPI).Clinical characteristics of H/TCRBCL patients showed a male predominance and a median age of 47 years. Performance status was normal in 89% of patients, whereas lactate dehydrogenase level was increased in 60% of patients. The disease was disseminated in 81% of patients, and 48% had two or more involved extranodal sites. The IPI score was >or= 2 in 53% of patients. The complete response rate to chemotherapy was 63%, and 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- SD) were 58% +/- 18% and 53% +/- 16%, respectively. The matched-control analysis showed a trend toward a better response to chemotherapy for patients with B-DLCL (P =.06), whereas no difference was observed in OS (P =.9) and EFS (P =.8).H/TCRBCL is an aggressive disease that often presents with adverse prognostic factors. However, when treatment is adapted to the disease risk, outcome is equivalent to that observed in patients with B-DLCL. Thus H/TCRBCL should be considered a pathologic variant that belongs to the B-DLCL category.