tbuckley/cabot-search huggingface dataset:
Continuous infusion intermediate-dose cytarabine, mitoxantrone, plus etoposide for refractory or early relapsed acute myelogenous leukemia
Authors: J.-H. Lee, S.-J. Choi, J.-H. Lee, Y.-S. Lee, M. Seol, S.-G. Ryu, J.-S. Lee, W.-K. Kim, K.-H. Lee
Journal: Journal of Clinical Oncology (2005)

6711 Background: Little attention has been paid to continuous infusion of intermediate- to high-dose cytarabine to increase the duration of drug exposure. We conducted a prospective phase II clinical trial to evaluate the efficacy and toxicity of continuous infusion intermediate-dose cytarabine-based salvage chemotherapy regimen in refractory and early relapsed AML. Methods: The chemotherapy regimen consisted of cytarabine (1 g/m2/d, 24-h iv infusion, d 1–5), mitoxantrone (12 mg/m2/d, short iv infusion, d 1–3), and etoposide (150 mg/m2/d, short iv infusion, d 1–3). Results: Of 33 patients enrolled in this study, 19 had refractory leukemia and 14 had relapsed leukemia. Seventeen patients (51.5%) achieved complete remission (CR). The cause of treatment failure was resistant leukemia in 13 and indeterminate in 3. Common severe non-hematologic toxicities were febrile neutropenia (87.9%), metabolic abnormalities (51.5%), gastrointestinal toxicities (27.3%), and hepatic toxicities (21.2%). These toxicities were manageable. Median duration of CR was 117 days and median overall survival was 219 days with 2 surviving patients in CR on 664 days and 1145 days after salvage chemotherapy. Conclusions: Continuous infusion intermediate-dose cytarabine along with mitoxantrone and etoposide could induce CR in significant portion of the patients with refractory or early relapsed AML, but remission duration was short. Continued efforts to improve treatment outcomes in patients with refractory or relapse AML should be made. No significant financial relationships to disclose.
A comparison of drug sensitivity pattern in category-I failure versus category-I relapse pulmonary TB patients attending a tertiary care hospital in South Punjab, Pakistan. Is WHO category-II ATT regimen appropriate?
Authors: M. Imran Shahzad, M. Azam Mushtaq, M. Zubair Shaheen, Humayyun Ghulam Murtaza
Journal: European Respiratory Journal (2013)

INTRODUCTION:  There are emerging reports of increasing number of patients with DR-TB in WHO category-ll patients.   OBJECTIVE:  To determine the pattern of DST in category-I failure and relapse pulmonary TB and see if currently recommended WHO Category-II regimen is appropriate for these two groups.   DESIGN: T otal of 88 patients in WHO category-II were evaluated prospectively for DST pattern on sputum cultures.   RESULTS:  N= 88, 33 (37%) Cat-I failure and 55(63%) Cat-I relapse. Among 33 Patients in Cat-1 failure, four (12%) cases were XDR-TB, 16 (48%) were MDR-TB, 5 (15%) were Polyresistant TB, 4 (12%) were Monoresistant and 4(12%) were sensitive to all drugs. A higher percentage, 65% (13/20 cases) of MDR/XDR-TB was found in Non-DOTS group as compared to DOTS group, 35 %.( 7/20 cases). Among 55 Patients in Cat-I relapse, four (7%) cases were XDR-TB, 20 (36%) were MDR-TB, 3 (5%) were Monoresistant, 3 (5%) were Polyresistant and 25 (45%) were sensitive to all drugs. A higher percentage, 55% (13/24 cases) of MDR/XDR-TB was found in DOTS group as compared to Non-DOTS group 45% (11/24).   Conclusion:  Our results suggest an urgent need to revise management strategies for both Category-I failure and relapse. Early TB culture and DST should be performed on these patients in order to avoid spread of MDR TB and its associated morbidity and mortality, by choosing correct regimen on the basis of DST results.
Increased intrahepatic quasispecies heterogeneity correlates with off-treatment sustained response to nucleos(t)ide analogues in e antigen-positive chronic hepatitis B patients
Authors: L. Chen, Q.R. Gan, D.Q. Zhang, L.F. Yao, R.S. Lin, Q. Li, M.H. Lin, D.M. Yu, X.X. Zhang, C. Pan
Journal: Clinical Microbiology and Infection (2015)
Guidelines for NHL: Updates to the Management of Diffuse Large B-Cell Lymphoma and New Guidelines for Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders and T-Cell Large Granular Lymphocytic Leukemia
Authors: Andrew D. Zelenetz
Journal: Journal of the National Comprehensive Cancer Network (2014)

During his presentation at the NCCN 19th Annual Conference, Dr. Andrew D. Zelenetz reviewed the updates to the 2014 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Hodgkin’s Lymphomas. Dr. Zelenetz first discussed the updates for diffuse large B-cell lymphoma (DLBCL), focusing primarily on the emergence of MYC-positive DLBCL; the limited role of imaging in early-stage disease; new treatment options; the challenge of tumor heterogeneity; and the impact of cell of origin in the selection of future therapies. Then, on behalf of Dr. Steven Horwitz, Dr. Zelenetz presented the new guidelines for primary cutaneous CD30+ T-cell lymphoproliferative disorders and T-cell large granular lymphocytic leukemia.
Abstract 16688: Human Cardiosphere-Derived Cells Stimulate Cardiomyocyte Proliferation in vivo and in Co-Culture
Authors: Yucai Xie, Ke Cheng, Hee Cheol Cho, Konstantinos Malliaras, Ahmed Ibrahim, Baiming Sun, Giselle Galang, Vittoria Ionta, Deliang Shen, Yiqiang Zhang, Eduardo Marban
Journal: Circulation (2011)

Background: Cardiosphere-derived cells (CDCs) are effective in regeneration after myocardial infarction (MI); however, direct differentiation of transplanted cells only accounts for a minuscule fra...
Irisin-encoding gene (FNDC5) variant is associated with changes in blood pressure and lipid profile in type 2 diabetic women but not in men
Authors: Letícia A. Brondani, Gabriela Boelter, Taís S. Assmann, Cristiane B. Leitão, Luís H. Canani, Daisy Crispim
Journal: Metabolism (2015)
Matrigel Mattress
Authors: Tromondae K. Feaster, Adrian G. Cadar, Lili Wang, Charles H. Williams, Young Wook Chun, Jonathan E. Hempel, Nathaniel Bloodworth, W. David Merryman, Chee Chew Lim, Joseph C. Wu, Björn C. Knollmann, Charles C. Hong
Journal: Circulation Research (2015)

Rationale: The lack of measurable single-cell contractility of human-induced pluripotent stem cell–derived cardiac myocytes (hiPSC-CMs) currently limits the utility of hiPSC-CMs for evaluating contractile performance for both basic research and drug discovery. Objective: To develop a culture method that rapidly generates contracting single hiPSC-CMs and allows quantification of cell shortening with standard equipment used for studying adult CMs. Methods and Results: Single hiPSC-CMs were cultured for 5 to 7 days on a 0.4- to 0.8-mm thick mattress of undiluted Matrigel (mattress hiPSC-CMs) and compared with hiPSC-CMs maintained on a control substrate (&lt;0.1-mm thick 1:60 diluted Matrigel, control hiPSC-CMs). Compared with control hiPSC-CMs, mattress hiPSC-CMs had more rod-shape morphology and significantly increased sarcomere length. Contractile parameters of mattress hiPSC-CMs measured with video-based edge detection were comparable with those of freshly isolated adult rabbit ventricular CMs. Morphological and contractile properties of mattress hiPSC-CMs were consistent across cryopreserved hiPSC-CMs generated independently at another institution. Unlike control hiPSC-CMs, mattress hiPSC-CMs display robust contractile responses to positive inotropic agents, such as myofilament calcium sensitizers. Mattress hiPSC-CMs exhibit molecular changes that include increased expression of the maturation marker cardiac troponin I and significantly increased action potential upstroke velocity because of a 2-fold increase in sodium current ( I Na ). Conclusions: The Matrigel mattress method enables the rapid generation of robustly contracting hiPSC-CMs and enhances maturation. This new method allows quantification of contractile performance at the single-cell level, which should be valuable to disease modeling, drug discovery, and preclinical cardiotoxicity testing.
Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy.
Authors: A Elias, L Ryan, A Sulkes, J Collins, J Aisner, K H Antman
Journal: Journal of Clinical Oncology (1989)

In this phase II trial, 105 eligible patients with no prior chemotherapy and advanced sarcoma received doxorubicin, ifosfamide, and dacarbazine (DTIC) with mesna uroprotection (MAID). Starting doses of these drugs were 60, 7,500, and 900 mg/m2 divided over 72 hours by continuous infusion, respectively. Mesna was given for 84 to 96 hours at 2,500 mg/m2/d. Myelosuppression was dose limiting, causing the only toxic death (sepsis). Nonhematologic toxicity consisted predominantly of anorexia and vomiting. Severe mucositis, macroscopic hematuria, renal tubular acidosis, renal failure, and CNS toxicity occurred in less than 5% of cycles. No cardiotoxicity was detected. The overall response rate (10% complete response [CR]) was 47% (95% confidence intervals, 5% to 18% and 37% to 57%, respectively). Most responses (approximately 70%) were observed within two cycles. Median times to progression were 10 and 9 months, respectively. Histologic high tumor grade, lesions less than 5 cm, and less than 1 year from diagnosis to study entry correlated with the probability of response. The median survival was 16 months. Time from diagnosis to study entry, performance status, and extent of disease, but not histologic grade, correlated with survival. Following CR, two patients remain disease-free at 32 and 16 months. Of the 15 additional patients rendered disease-free with surgery, two remain disease-free at 30 and 18 months with no further therapy. While most relapses occurred in sites of prior involvement, death from CNS metastases occurred in 11 of the 80 patients with high-grade sarcomas, of whom seven were still responding systematically (three complete responders). Because of its substantial response in this phase II trial, the MAID regimen is being compared with doxorubicin and DTIC alone in advanced sarcomas and to observation in the adjuvant treatment of high-grade sarcomas in randomized trials.
Comparison of the prognostic value of different severity scales in community- acquired pneumonia
Authors: Darina Miteva, Vanya Kostadinova, Yordan Radkov, Iskra Mircheva
Journal: European Respiratory Journal (2014)

Background: Severity scores are used to determine prognosis of community-acquired pneumonia (CAP).   Aim: To compare prognostic value of CURB65 and CRB65 scores, Pneumonia severity index (PSI) and IDSA/ATS severity criteria for Intensive care unit admission (ICU) and in-hospital mortality in patients hospitalized with CAP.   Methods: A retrospective survey for the period of 1year. It includes 408 hospitalized patients with CAP, average age 61,3±16,7 years;59,6% men (n=243). Receiver operating characteristics (ROC) curve and t-test analysis were used.   Results:  PSI (AUC=0,866) is superior to CURB65 (AUC=0,844), CRB65 (AUC=0,831)and IDSA/ATS criteria (AUC=0,827)in predicting the need of intensive care (p  PSI and IDSA/ATS criteria can predict the total in-hospital mortality better than CURB65 and CRB65 (AUC=0,861; 0,859; 0,849 and 0,842, respectively). Mean PSI score in survivors is 88,4 and in non-survivors – 160,9 (t=-12,824; p  The PSI class, IDSA/ATS criteria, CURB65 and CRB65 scores classified 39,4%, 18,9%, 21,5% and 20,1% as severe CAP, respectively.   Conclusion: Although PSI is the most reliable tool in predicting the need of intensive care, IDSA/ATS criteria have greater discriminatory power for the prognosis of early in-hospital mortality. Both, PSI and IDSA/ATS criteria, are similar in predicting total in-hospital mortality.
Abstract 19488: Serpin-8 Prevents Migration of Macrophages by Inhibiting a Proprotein Convertase-Driven Activation of MT1-MMP
Authors: Daniel Urban, Jan Fritzsche, Heike Meýborg, Kai Kappert, Eckart Fleck, Philipp Stawowy
Journal: Circulation (2010)

Introduction: Accumulation of macrophages and their expression of matrix metalloproteinases (MMPs) play a pivotal role for the induction and progression of atherosclerotic plaque instability. Recen...
Reference values for the 6-minute walk test in healthy children
Authors: Silvia Ulrich, Florian Hildenbrand, Ursula Treder, Manuel Fischler, Rudolf Speich, Margrit Fastnacht
Journal: European Respiratory Journal (2012)

Background:  The 6 minute walk test (6MWT) is a simple and reliable tool to assess exercise capacity in various diseases. The aim of this study was to establish reference values for the 6MWT in healthy children and adolescents in middle Europe and to investigate the impact of age, anthropometrics, heart rate, blood pressure and reported physical activity on the distance walked.   Methods : Age- and sex-stratified children and adolescents between 5-17 years had short questionnaire assessments about their health state and physical activities. Thereafter anthropometrics and vitals were measured, a 6MWT was performed according to guidelines and exercise vitals were reassessed.   Results:  Age-adjusted 6MWT distance from 496 children (252 girls) was obtained. Age, height, weight and the exercise heart rate all predicted the distance walked according to different regression models: age was the best single predictor and mostly influenced walk distance in younger age, anthropometrics were more important in girls and adolescents. Exercise heart rate was an important distance predictor in addition to age and outreached anthropometrics in the majority of subgroups assessed.   Conclusion : Performing the 6MWT is feasible and practical in children and adolescents. The 6MWD depends mainly on age, however, exercise heart rate, height and weight significantly add information and should be taken into account mainly in adolescents. Reference equations allow to predict 6MWT distance and may help to better assess and compare outcomes in young patients with cardiovascular diseases.
Phase I trial of gemcitabine and split-dose cisplatin plus everolimus (RAD001) in patients with advanced urothelial cancer.
Authors: Wassim Abida, Matthew I. Milowsky, Irina Ostrovnaya, Scott R. Gerst, Jonathan E. Rosenberg, Ashley Marie Regazzi, Asia S. McCoy, Mariel Elena Boyd, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2015)

322 Background: Gemcitabine and split-dose cisplatin (GC) is standard first-line therapy for patients with advanced urothelial cancer (UC). Everolimus is an inhibitor of the PI3K/AKT/mTOR pathway, dysregulated in ~35% of UCs. The drug has been shown to have single-agent activity in phase II trials of advanced UC. The safety of combining everolimus with GC in the first-line setting for UC is unknown. Methods: Previously untreated cisplatin-eligible patients with advanced UC were enrolled. Patients received gemcitabine 800 mg/m2 and cisplatin 35mg/m2 on days 1 and 8 with everolimus at dose levels (DL1: 5 mg QOD, DL2: 5 mg daily or DL3: 10 mg daily) for six 21-day cycles. Patients with at least SD continued maintenance everolimus until progression. Restaging evaluations were performed every 2 cycles. The primary objective was to establish the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the three-drug combination. Results: 12 patients were enrolled, 7 with bladder and 5 with upper tract primaries. 4/12 patients completed at least 6 cycles. 0/3 patients at DL1 had DLTs. 3/3 patients at DL2 had DLTs (pancytopenia, hypersensitivity reaction to everolimus and anemia). Following de-escalation to DL1, 2/6 patients in a new DL1 cohort had DLTs (neutropenia and diarrhea, 1/6 patients inevaluable). Grade 3/4 events included anemia (67%), neutropenia (42%), lymphopenia (42%), thrombocytopenia (25%), urinary tract infection (25%), hypomagnesemia (17%), and hypophosphatemia (17%). Tumor responses included: 4 PR (33%), 5 SD (42%), 1 PD (8%), and 2 inevaluable (17%). 2 patients with PR underwent consolidative surgery but eventually progressed. Responses by MSKCC Risk Scores of 0, 1, and 2 were seen in 3/5 (60%), 1/6 (17%), and 0/1 patients, respectively. Median PFS was 3.9 months (95% CI, 3.7-no reached) and median OS was 10.8 months (95% CI, 6.9-not reached). Conclusions: MTD was reached at DL1 for combination gemcitabine, split-dose cisplatin and everolimus, with 2/8 evaluable patients exhibiting DLTs at this dose level. Clinical trial information: NCT01182168.
Epidemiological surveys might underestimate waterpipe smoking
Authors: M. Jawad, C. Millett
Journal: BMJ (2015)

Maziak details a worrisome rise in waterpipe tobacco smoking, particularly among adolescents and young adults.1 Surveillance on a national level is paramount to understanding the epidemiology of waterpipe smoking, and we have two concerns about the approaches used to monitor the global prevalence of waterpipe use.

Firstly, data from …
Regulatory T cells in pulmonary arterial hypertension
Authors: Alice Huertas, Ly Tu, Natalia Gambaryan, Barbara Girerd, David Montani, Christophe Guignabert, Marc Humbert
Journal: European Respiratory Journal (2013)

Increasing evidences support the hypothesis that immune mechanisms may play a key role in pulmonary arterial hypertension (PAH) onset or progression, but the underlying mechanisms are still unclear. We have recently shown that regulatory T cells (Treg) are dysfunctional in idiopathic PAH (iPAH) in a leptin-dependant manner (Huertas, A. et al. ERJ 2012; 40:895-904). Despite these findings, it is still unknown whether the immunopathogenesis is similar among all PAH forms, and whether these immune mechanisms can be controlled to block PAH onset and/or progression.  Here, we first analyzed circulating Treg functional status in different groups of PAH patients: iPAH (n=25), heritable (hPAH, n=20), pulmonary veno-occlusive disease (PVOD, n=10), scleroderma-associated (SSc-PAH, n=11) and we compared them to controls (n=20) by flow cytometry. We found that STAT3 phosphorylation is decreased in Treg in all PAH groups as compared to controls, underlying the key role of Treg dysfunction in PAH pathogenesis. We also demonstrated that Treg are inhibited in a leptin-dependent manner in all PAH groups, except for hPAH. To elucidate the leptin-dependent immune mechanisms in PAH onset, we used rats deficient in leptin receptor (ZDF-/-) in a chronic hypoxia-induced model of pulmonary hypertension (Hx-PH). Strikingly, Hx-PH ZDF-/- rats maintain functional Treg and they develop less severe Hx-PH as compared to wildtype controls. Taken together, our results clearly indicate a crucial role for Treg in PAH immunopathogenesis, highlighting that Treg dysfunction may represent an important “second hit” in PAH onset and/or progression. These results shed light on new promising therapeutical targets in PAH treatment. Support: FRM Josso Award 2010.
Combined Effect of X Radiation and 5-Fluorouracil on Survival of Transplanted Leukemic Cells&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Teresa Vietti, Faye Eggerding, Fred Valeriote
Journal: JNCI Journal of the National Cancer Institute (1971)

The effect of 5-fluorouracil (5-FU) and X radiation on the survival of transplanted leukemic cells was studied in syngeneic AKR mice. A single intravenous injection of 0.6 mg 5-FU reduced the surviving fraction of leukemic cells to 10-2 of the untreated control. A similar reduction in the surviving fraction was found after 400 R total-body radiation. However, a marked synergistic cytocidal response was observed when 5-FU was given within 8 hours after radiation. The degree of synergism was less if the drug was given before radiation. In this case, the synergistic effect was greatest when 5-FU was given 14–24 hours preceding radiation. Hopefully, this study will serve to initiate closely supervised clinical trials with these two agents in combination, on which a more rational clinical treatment regimen can be formulated.
Adrenocortical carcinoma in children: a study of 40 cases.
Authors: R C Ribeiro, R S Sandrini Neto, M J Schell, L Lacerda, G A Sambaio, I Cat
Journal: Journal of Clinical Oncology (1990)

Adrenocortical carcinoma (ACC), a very rare tumor in children in the United States, is apparently more common among Brazilian children. We reviewed the medical records of 40 children whose disease was diagnosed between 1966 and 1987. There were 12 boys and 28 girls; their median age was 3.9 years (range, 1 day to 15.7 years). Virilization was the most common clinical sign (37 of 40); other signs included abdominal mass, deepened voice, plethora, hypertension, seizures (seven patients) and, rarely, weight loss (two patients). The median time between first signs or symptoms and diagnosis was 1.4 years (range, 3 days to 5 years). Four of 33 tumors were classified as benign according to the Weiss, van Slooten, or Hough systems (tumor tissue was unavailable for seven patients). Tumors were completely resected in 26 of 38 patients; of those, 17 are in continuous complete remission, five relapsed, and four have been lost to follow-up. One patient, who had local recurrence, has been in a third complete remission for 18+ months after tumor resection and chemotherapy (cisplatin and etoposide). Of the remaining 14 patients, 11 died of progressive disease, the diagnosis was confirmed at autopsy in two, and one has been lost to follow-up. Univariate analysis disclosed that age greater than or equal to 3.5 years at diagnosis, interval of greater than or equal to 6 months between first symptoms and diagnosis, tumor weight greater than 100 g, tumor size greater than 200 cm3, and high levels of urinary 17-ketosteroids (17-KS) and 17-hydroxycorticosteroids (17-OH) were associated with an unfavorable outcome. Multivariate analysis disclosed that only a tumor size greater than 200 cm3 independently identifies those patients with an unfavorable prognosis. Among the variables known before surgery, age, and the interval between first symptoms and diagnosis were important predictors of outcome. Our data suggest that some children with ACC and certain clinical characteristics are at high risk of primary treatment failure and, therefore, are good candidates for investigational adjuvant therapy.
Pulmonary hypertension correction in patients with chronic obstructive pulmonary disease and essential hypertension
Authors: Olga Yakovleva, Tatiana Masloiid, Alexandra Klekot
Journal: European Respiratory Journal (2014)

Background Essential hypertension (EH) and COPD are the most frequent comorbid conditions.COPD is often complicated by pulmonary hypertension (PH), which affects the course and prognosis of the disease.  Objective was to estimate the effect of the combinend antihypertensive therapy of EH on the level of PH depending on the stage of bronchoobstruction in COPD patients.  Methods 48 patients (37 males and 11 females) with COPD of moderate and severe bronchial obstruction complicated by PH and with essential hypertension were studied. Mean pressure in the pulmonary artery (PA) was determined by Doppler-echocardiography. PH was diagnosed at a pulmonary artery (PA) pressure ≥36 mm Hg. In addition to the treatment of COPD was used a combinated antihypertensive therapy: amlodipine at daily dose of 5 mg and an ramipril at daily dose of 5 mg. The observation lasted 3 months.  Results The mean age of patients was 51,88 ± 2,26 years. Antihypertensive drugs usage decreased the PA pressure in COPD patients with moderate bronchial obstruction on 36.72%, and in COPD patients with severe obstruction - on 24.19% (p  Conclusions Amlodipine and ramipril on the background of the basic treatment of COPD has a positive effect on the blood pressure dynamics in the pulmonary artery and at the system circulationl that encourages their use in this group of patients.