tbuckley/cabot-search huggingface dataset:
Stent Retrievers for the Treatment of Acute Ischemic Stroke
Authors: Lahoud Touma, Kristian B. Filion, Lee H. Sterling, Renée Atallah, Sarah B. Windle, Mark J. Eisenberg
Journal: JAMA Neurology (2016)

Stent retrievers are a promising alternative for the treatment of acute ischemic stroke (AIS). Several recently completed clinical trials have examined the use of stent retrievers with intravenous recombinant tissue plasminogen activator (rtPA) compared with rtPA alone.To conduct a systematic review and meta-analysis of randomized clinical trials to quantify the benefits and risks of using stent retrievers in addition to rtPA for the treatment of AIS.The MEDLINE, EMBASE, and Cochrane Library of Clinical Trials databases were searched from inception to July 2015 for the keywords stent*, retriev*, Solitaire, Trevo, Revive, and stroke. Trial registries were also searched. A total of 326 publications were identified and 213 potentially relevant records were screened.Randomized clinical trials that examined stent retrievers with rtPA vs rtPA alone were included in the meta-analysis.Two independent reviewers extracted study data and performed quality assessment using the Cochrane Risk of Bias Tool. DerSimonian and Laird random-effects models were used to estimate relative risks (RRs), risk differences (RDs), and numbers needed to treat.The primary outcome was the proportion of patients achieving functional independence (defined as a score of 0-2 on the modified Rankin Scale, with 0 indicating no disability and 6 indicating death) at 90 days. Risks of all-cause mortality, intracranial hemorrhage, and parenchymal hematoma at 90 days were also assessed.Five randomized clinical trials met our inclusion criteria (n = 1287 patients). Patients randomized to stent-retriever therapy with rtPA had significantly improved rates of functional independence at 90 days compared with those randomized to rtPA alone (RR, 1.72; 95% CI, 1.48-1.99; RD, 0.19; 95% CI, 0.13-0.25). When data were pooled across trials, the effect of stent-retriever therapy on all-cause mortality at 90 days was inconclusive (RR, 0.82; 95% CI, 0.60-1.11; RD, -0.04; 95% CI, -0.08 to 0.1). There were similarly no detectable differences in the risks of intracranial hemorrhage (RR, 1.15; 95% CI, 0.67-1.97; RD, 0.00; 95% CI, -0.02 to 0.03) or parenchymal hematoma (RR, 1.18; 95% CI, 0.71-1.94; RD, 0.01; 95% CI, -0.01 to 0.04), although the 95% CIs were wide. Fixed-effects sensitivity analyses produced similar results for all outcomes.The use of stent retrievers in conjunction with rtPA vs rtPA alone is associated with significant improvement of functional independence 90 days after AIS.
Abstract 216: Traditional Chinese Medicine Tongxinluo Modulates The Secretion Of Cytokines In Vitro By Cardiac Microvascular Endothelial Cells In Ischemia/Reperfusion Injury.
Authors: Hehe Cui, Xiangdong Li, Zhigang Wang, Na Li, Kang Qi, Qing Li, Chen Jin, Yuejin Yang
Journal: Circulation Research (2014)

Cardiac microvascular endothelial cells (CMECs) regulate the function of cardiomyocytes and blood cells in myocardial ischemia/ reperfusion injury (MIRI) via paracrine methods. Tongxinluo (TXL) is a Traditional Chinese Medicine compound to treat angina pectoris in China, which is constituted of ginseng and other 11 natural products. It is proved to improve the endothelial function and be protective against MIRI. Thus, we aimed to find alterations in paracrine function of CMECs under the hypoxia/reoxygenation (H/R) situation and its modulation by TXL. CMECs were exposed to different concentrations of TXL for 30 min and then subjected to H/R for 12 h/2 h. Apoptotic rates were measured to determine the optimal concentration. Protein antibody arrays were used to find the alterations of cytokines in conditioned medium (CM) secreted by CMECs. Gene Ontology project was adopted to describe the functions of changed cytokines. TXL inhibited apoptosis of CMECs dose-dependently under H/R and reached its peak effect at 800 μg/mL. Thirty-three types of cytokines were significantly changed by H/R (19 factors decreased and 14 increased), and TXL at 800μg/ml changed 121 types of cytokines compared to the H/R group (93 factors decreased and 28 increased). The cytokines with significant alterations were involved in cell differentiation and proliferation, positive chemotaxis, and endothelial cell migration. Among these cytokines, bFGF, PDGF and IL-7 were attenuated by H/R and further decreased by TXL, while IL-21, MCP-2 and GROa were increased by H/R but decreased by TXL. The study elucidated the paracrine function of CMECs in MIRI and partly illuminated the protective mechanisms of TXL.
Peer review of statistics in medical research
Authors: M. Zwarenstein
Journal: BMJ (2002)

# Journal reviewers are even more baffled by sample size issues than grant proposal reviewers {#article-title-2} EDITOR—With reference to the article by Bacchetti,1 the confusion surrounding sample size estimates in research protocols elicits quite strange responses from reviewers when they are faced with the completed research in a report submitted to a journal for publication. One of our submissions was rejected because the planned sample size was not attained. But the effect size was greater in the study than we had anticipated, and thus the difference was of clinical and statistical significance. Another submission met the same fate for a similar reason—it was an equivalence trial—and even though the difference in effect between intervention and control arms (and both sides of the confidence interval around this difference) lay completely within the equivalence interval, the fact that the planned sample size was not attained in some way invalidated the result in the mind of the reviewer. Although sample size estimation is useful in considering the feasibility of conducting a study (and protocol reviewers should discourage funding for studies that are plainly too small to be meaningful) attainment of the planned sample size does not seem to me to be a useful indicator by which journal reviewers should assess the validity of a completed research report in which clinically and statistically meaningful results have been obtained. 1. 1.↵1. Bacchetti P .Peer review of statistics in medical research: the other problem.BMJ2002; 324:1271–1273. (25 May.) [OpenUrl][1][FREE Full Text][2] # Rationale for requiring power calculations is needed {#article-title-4} EDITOR—The article by Bacchetti with its comments about uncertainties surrounding power calculations prompted me to seek advice about an issue that has implications for clinical research.1 The company I work for, Laxdale Limited, often conducts pilot studies on new entities. Our usual practice is to state in the protocol that there is no reasonable basis for a power calculation. In order … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DBacchetti%26rft.auinit1%253DP.%26rft.volume%253D324%26rft.issue%253D7348%26rft.spage%253D1271%26rft.epage%253D1273%26rft.atitle%253DPeer%2Breview%2Bof%2Bstatistics%2Bin%2Bmedical%2Bresearch%253A%2Bthe%2Bother%2Bproblem%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.324.7348.1271%26rft_id%253Dinfo%253Apmid%252F12028986%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=bmj&resid=324/7348/1271&atom=%2Fbmj%2F325%2F7362%2F491.2.atom
Second cancer risk following testicular cancer: a follow-up study of 1,909 patients.
Authors: F E van Leeuwen, A M Stiggelbout, A W van den Belt-Dusebout, R Noyon, M R Eliel, E H van Kerkhoff, J F Delemarre, R Somers
Journal: Journal of Clinical Oncology (1993)

PURPOSE Improved survival in testicular cancer has been accompanied by concern about long-term side effects of therapy. We assessed the evolution of second cancer (SC) risk over a prolonged follow-up period, which has been rarely studied in large patient series. PATIENTS AND METHODS We estimated the risk of SCs in 1,909 patients with testicular cancer diagnosed in the Netherlands from 1971 to 1985. Complete medical information was obtained up to at least January 1988 for 92% of patients. Median follow-up was 7.7 years. For 89% of second tumors the diagnosis was confirmed through review of histologic slides; for an additional 8%, the diagnosis was verified by pathology reports only. RESULTS Seventy-eight patients developed a SC 1 year or more after start of treatment, as compared with 47.6 expected on the basis of incidence rates in the general population (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3 to 2.1). The mean 15-year actuarial risk of all SCs was 9.8% (95% CI, 7.5% to 12.8%). Significantly increased RRs were observed for all gastrointestinal cancers combined (RR, 2.6; 95% CI, 1.7 to 3.9), stomach cancer (RR, 3.7; 95% CI, 1.8 to 6.8), contralateral testicular cancer (CLTC) (RR, 35.7; 95% CI, 21.8 to 55.2), and leukemia (RR, 5.1; 95% CI, 1.4 to 13.0). Patients who had received irradiation to the paraaortic lymph nodes and who survived testicular cancer for more than 5 years were at particularly high risk of developing stomach cancer (RR, 6.9; 95% CI, 3.3 to 12.7). The median interval between the diagnosis of testicular cancer and stomach cancer was 12.4 years. Patients treated with chemotherapy (CT) did not experience an increase in SCs in general. Indeed, CT-treated patients, as compared with those who received radiotherapy (RT), or surgery alone, had significantly reduced risk of CLTC. This finding might be attributed to an eradicating effect of CT on carcinoma in situ or subclinical CLTC. The excess risk of leukemia was not found to be clearly related to CT. CONCLUSION Testicular cancer patients who receive RT experience elevated risk of gastrointestinal tumors. CT does not seem to increase SC risk and may even decrease the risk of a CLTC. Following testicular cancer, the 15-year actuarial risk of all SCs is only about half the risk experienced by patients with Hodgkin's disease.
Improved access to HER2 testing and trastuzumab therapy for patients with metastatic breast cancer in Northern Ireland from 2004 to 2007
Authors: P. Scullin, V. M. Coyle, J. O’Hare, S. McAleer
Journal: Journal of Clinical Oncology (2008)

17532 Background: Clinical trials have established that patients receiving taxane-based chemotherapy for metastatic breast cancer (MBC) should be treated with trastuzumab if their tumour is shown to overexpress the human epidermal growth factor receptor 2 (HER2) receptor. A previous audit carried out in Northern Ireland throughout 2004 identified that some patients who were receiving chemotherapy for MBC did not have HER2 testing or trastuzumab where indicated and that the time to obtain a result averaged 41.5 days. This re-audit examined the same issues given that results of the previous audit were widely disseminated and that testing of HER2 status is now performed at diagnosis. Methods: Patients commencing chemotherapy for MBC in Northern Ireland in the first quarter of 2007 were identified from pharmacy records. Their case notes were retrospectively reviewed to determine whether patients in routine clinical practice had HER2 testing and trastuzumab treatment if indicated. Results: Fifty six patients commenced chemotherapy. HER2 data is available for 52 patients, of whom 51 (98%) had HER2 testing, compared to 93% in 2004. The patient who did not have HER2 testing was not suitable for trastuzumab therapy. In 50 (98%) patients the HER2 result was already available at the time of this relapse compared with 44% in 2004. In the remaining 1 patient the result became available in 9 days compared with a median of 41.5 days in 76 (49%) patients in 2004. Of those tested, 21 patients (41%) were HER2 positive. Eighteen of these patients were treated with trastuzumab. There were valid reasons for trastuzumab omission in the 3 patients not given trastuzumab. Conclusions: In our region all of the 52 patients who received chemotherapy for MBC and for whom data is currently available for, were tested for overexpression of the HER2 receptor. Of those patients who were eligible to receive trastuzumab all received trastuzumab, compared with 91% of patients in the 2004 audit. In most cases the HER2 status was known at the time of relapse and the time required to obtain a HER2 result was 9 days compared with a median of 41.5 days in 2004. No significant financial relationships to disclose.
Palliative first-line chemotherapy of patients with metastatic colorectal cancer with 5-FU/FA as a 24h-inf. (AIO schedule) combined with weekly Irinotecan and bi-weekly Bevacizumab (BV): Interim analysis of a prospective evaluation
Authors: F. Boxberger, H. Albrecht, U. Reulbach, G. Maennlein, W. Hohenberger, E. G. Hahn, A. Wein
Journal: Journal of Clinical Oncology (2008)

15099 Background: BV is a humanized monoclonal antibody that targets vascular endothelial growth factor and downregulates angiogenesis. Since 2005 BV is licensed for the first-line treatment of patients (pts.) with metastatic colorectal cancer (CRC). The most effective treatment schedule applied in combination with BV which provides the lowest grade of toxic side effects is still unknown to date. Here, we report on the interim analysis of metastatic CRC pts., who have been treated with palliative first-line chemoth. based on 5-FU/FA as a 24h- inf. (AIO) combined with a weekly application of Irinotecan and bi-weekly BV. Methods: Prospective evaluation of 21 pts. in the framework of an application monitoring based on the tumor registry data of the Dept. of Int. Med. 1; start: 1.2.2005; palliative chemoth.: BV (5mg/kg i.v. as 0,5h-inf.; d1,15,29 qd57) and Irinotecan (80 mg/m2 i.v. as 1h-inf.; d1,8,15,22,29,36 qd57) followed by 5-FU (2,000 mg/m2 i.v. as 24h-inf.; d 1,8,15,22,29,36 qd57) and FA (500 mg/m2 i.v. as 24h-inf.; d1,8,15,22,29,36 qd57) via a miniature pump system. Results: Last date of evaluation: Nov/30/07; localisation: colon: 47.6%, rectum: 47.6%, unknown: 4.8%; histology: adenocarcinoma: 90.4%, signet-ring cell carcinoma: 4.8%, undifferentiated carcinoma: 4.8%; grading G2/G3: 81/19%; metastases: liver: 81%, peritoneum: 28.6%, lungs: 38.1%; median age: 54 years; men/women: 52.4/47.6%; ECOG 0/1/2: 42.8/52.4/4.8%; chemoth. appl.: total number: 386; higher grade toxicity (grade 3+4): anemia: 4.8%, diarrhea: 14.3%, hypertonia: 14.3%, pain: 4.8%, alopecia: 4.8%, intestinal fistula: 4.8%, thrombembolic events: 19%; response: CR: 9.5%, PR: 19%, SD: 66.7%, not evaluable: 4.8%; tumor control (CR, PR, SD): 95.2%; secondary metastatic resection: R0: 23.8%, R2: 14.3%, RX: 4.8%. Conclusion: Combination chemoth. with weekly Irinotecan and bi-weekly BV followed by 5-FU/FA as a 24h-inf. (AIO) on an out-patient basis is an effective palliative treatment schedule with solely low grade toxicity. Final results remain to be seen. No significant financial relationships to disclose.
Cryobiopsy versus forceps biopsy during semirigid thoracoscopy
Authors: Ales Rozman, Mateja Marc-Malovrh, Luka Camlek, Izidor Kern
Journal: European Respiratory Journal (2012)

Performing biopsies during semirigid thoracoscopy is often a difficult and time-consuming task due to the low mechanical power when using dedicated flexible forceps. Biopsies by cryoprobe could overcome these limitations. The purpose of this study was to compare the feasibility, size and quality of the specimens obtained by cryobiopsy with specimens obtained by flexible forceps.  Fifteen patients with pleural effusion of unknown origin that underwent semirigid thoracoscopy were included. Biopsies were obtained using a flexible autoclavable cryoprobe 20416-032 (ERBE, Germany) 2.4 mm in diameter or flexible FB-55CD-1 Olympus forceps.  Tissue samples were obtained from all 15 patients by forceps and from 14 patients by cryobiopsy, three with each technique per patient. The median size of the cryobiopsy sample was 17.1 (3.9–86.7) mm² and 9.1 (2.3-27.2) mm² of the forceps sample. Cryobiopsy samples were easier for interpretation (p = 0.003) than forceps biopsy samples. The amount of artifacts wasn9t statistically different between groups (p = 0.285). Diagnostic yield was the same by both techniques in patients, where both types of samples were obtained. There were no bleeding problems after the biopsies.  Cryobiopsy during semirigid thoracoscopy appears to be an effective and safe new method for obtaining biopsy specimens from the pleural cavity. Cryobiopsy samples were bigger than samples, obtained by flexible forceps. The quality and diagnostic yield were comparable.
A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors
Authors: Marina Bacac, Tanja Fauti, Johannes Sam, Sara Colombetti, Tina Weinzierl, Djamila Ouaret, Walter Bodmer, Steffi Lehmann, Thomas Hofer, Ralf J. Hosse, Ekkehard Moessner, Oliver Ast, Peter Bruenker, Sandra Grau-Richards, Teilo Schaller, Annette Seidl, Christian Gerdes, Mario Perro, Valeria Nicolini, Nathalie Steinhoff, Sherri Dudal, Sebastian Neumann, Thomas von Hirschheydt, Christiane Jaeger, Jose Saro, Vaios Karanikas, Christian Klein, Pablo Umaña
Journal: Clinical Cancer Research (2016)

CEA TCB is a novel IgG-based T-cell bispecific (TCB) antibody for the treatment of CEA-expressing solid tumors currently in phase I clinical trials (NCT02324257). Its format incorporates bivalent binding to CEA, a head-to-tail fusion of CEA- and CD3e-binding Fab domains and an engineered Fc region with completely abolished binding to FcγRs and C1q. The study provides novel mechanistic insights into the activity and mode of action of CEA TCB.CEA TCB activity was characterized on 110 cell lines in vitro and in xenograft tumor models in vivo using NOG mice engrafted with human peripheral blood mononuclear cells.Simultaneous binding of CEA TCB to tumor and T cells leads to formation of immunologic synapses, T-cell activation, secretion of cytotoxic granules, and tumor cell lysis. CEA TCB activity strongly correlates with CEA expression, with higher potency observed in highly CEA-expressing tumor cells and a threshold of approximately 10,000 CEA-binding sites/cell, which allows distinguishing between high- and low-CEA-expressing tumor and primary epithelial cells, respectively. Genetic factors do not affect CEA TCB activity confirming that CEA expression level is the strongest predictor of CEA TCB activity. In vivo, CEA TCB induces regression of CEA-expressing xenograft tumors with variable amounts of immune cell infiltrate, leads to increased frequency of activated T cells, and converts PD-L1 negative into PD-L1-positive tumors.CEA TCB is a novel generation TCB displaying potent antitumor activity; it is efficacious in poorly infiltrated tumors where it increases T-cell infiltration and generates a highly inflamed tumor microenvironment. Clin Cancer Res; 22(13); 3286-97. ©2016 AACR.
Concomitant administration of recombinant human interleukin-2 and recombinant interferon alpha-2A in cancer patients: a phase I study.
Authors: K H Lee, M Talpaz, J M Rothberg, J L Murray, N Papadopoulos, C Plager, R Benjamin, D Levitt, J Gutterman
Journal: Journal of Clinical Oncology (1989)

Twenty-seven patients with metastatic cancer were treated with a daily continuous intravenous (IV) infusion of recombinant human interleukin-2 (rhIL-2) along with daily intramuscular recombinant interferon-alpha-2a (rIFN-alpha-2a) 4 days per week for 4 weeks with repeated treatment after 2 to 4 weeks of rest. The maximum-tolerated dose (MTD) was 3 million U/m2/d of rhIL-2 with 5 to 10 million U/m2/d of rIFN-alpha-2a. The dose-limiting toxicities are moderate hypotension requiring low doses of pressors and chronic fatigue associated with decreased performance status. Other common side effects included fever, chills, fluid retention, nausea/vomiting, erythrodermia, weight loss, elevated liver transminase levels, anemia, thrombocytopenia, and CNS toxic effects. There were seven objective responses among 25 evaluable patients. Four major responses (one complete response and three partial responses) were observed among 10 patients with melanoma treated with the MTD level. These data suggest that for cancer patients, concomitant rhIL-2 and rIFN-alpha-2a therapy is tolerable and has manageable side effects. Further phase II studies will be needed to define the antitumor activity of this combination.
First-line treatment of acute promyelocytic leukemia with arsenic trioxide without ATRA and chemotherapy
Authors: A. Ghavamzadeh, K. Alimoghaddam, S. Ghaffari, S. Rostami, M. Jahani, A. Khodabandeh, S. Mossavi, M. Iravani, E. Eini, Z. Moghadam, F. Afshar
Journal: Journal of Clinical Oncology (2007)

7073 Background: Standard treatment of APL is ATRA plus chemotherapy but Arsenic Trioxide (ATO) is most potent single agent against APL cells. Role of ATO in first line therapy of APL needs to clarify. Methods: Between may 2000 and September 2006,we treated 141 new cases of APL(Median age 28±12.8 y/o min=11,max=71) by 2 hours iv infusion of 0.15mg/kg ATO until complete remission. Trial approved by IRB and consent form obtained. Diagnosis was by clinical and morphologic characteristics and confirmed by cytogenetic and RT-PCR for detection of t(15,17) and presence of PML-RARa. After complete remission patients received consolidation by 28 days infusion of ATO for one or four courses.(one consolidation one month after CR and for some patients second, third and forth consolidations one month after first one and two another , one year and two year after CR) Results: : complete remission observed in 121 cases(85.8%) and early mortality rate was14.9%(most common cause of early mortality was APL syndrome,61.9%).Median follow up was 28 months. For patients who achieve to complete remission,one, two and three year disease free survival were 95.6%± 2%, 76.9±4% and 57± 6%,respectively. Many relapsed patients salvaged again with ATO alone so, two and three years overall survival for this cohort was 95.6%±2% and 83.7%±4%. Increasing number of consolidation from one to four couldn’t increase DFS or OS in one and two years after CR. Conclusions: ATO is effective in treatment of new cases of APL. Introduction of ATO in first line treatment of APL(with or without ATRA plus chemotherapy) needs a multi center randomized clinical trial. No significant financial relationships to disclose.
Docetaxel and cisplatin in metastatic urothelial cancer: a phase II study.
Authors: L Sengeløv, C Kamby, B Lund, S A Engelholm
Journal: Journal of Clinical Oncology (1998)

PURPOSE Docetaxel and cisplatin has documented single-agent activity and different toxicity profiles in patients with metastatic urothelial cancer. We performed a phase II study in which docetaxel was combined with cisplatin to evaluate response rate, toxicity, and survival. PATIENTS AND METHODS Eligibility criteria included performance status (World Health Organization [WHO]) less than 3; normal bone marrow, liver, and renal function; and no concurrent malignancy or symptomatic peripheral neuropathy. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Paris, France) 75 mg/m2 was combined with cisplatin 75 mg/m2 every third week. Patients received premedication with prednisolone and clemastine. RESULTS A total of 25 patients were assessable for response and toxicity. Median age was 64 years; five patients had locoregional disease only and 20 had metastatic disease. Response was achieved in 15 patients (60%; 95% confidence interval [CI], 39% to 79%), including seven patients (26%) who achieved a complete response. Overall median survival time was 13.6 months (range, 1.5 to 26.4+). The most frequent toxicity was nausea and vomiting (80% of patients). Neutropenia grade 3 or 4 was observed in 56% of patients, but only one had febrile neutropenia. Mucositis and diarrhea were encountered in 13% of cycles, mostly grade 1 or 2. Peripheral neuropathy and skin changes grade 1 and 2 were observed in 76% and 36%, respectively. Fluid retention and hypersensitivity reactions were infrequent and mild. CONCLUSION The combination of docetaxel and cisplatin is effective and feasible in patients with metastatic urothelial cancer with a manageable safety profile.