tbuckley/cabot-search huggingface dataset:
Comparison of Gonadotropin-Releasing Hormone Agonists and Orchiectomy
Authors: Maxine Sun, Toni K. Choueiri, Ole-Petter R. Hamnvik, Mark A. Preston, Guillermo De Velasco, Wei Jiang, Stacy Loeb, Paul L. Nguyen, Quoc-Dien Trinh
Journal: JAMA Oncology (2015)

Androgen-deprivation therapy (ADT) through surgical castration is equally effective as medical castration in controlling prostate cancer (PCa). However, the adverse effect profiles of both ADT groups have never been compared.To provide a comparative effectiveness analysis of the adverse effects of gonadotropin-releasing hormone agonists (GnRHa) vs bilateral orchiectomy in a homogeneous population.A population-based cohort of 3295 men with metastatic PCa between January 1995 and December 2009 66 years or older was selected from the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database.Orchiectomy or GnRHa.Any fractures, peripheral arterial disease, venous thromboembolism, cardiac-related complications, diabetes mellitus, and cognitive disorders. To minimize treatment group biases, the inverse probability of treatment was weighted using the propensity score. Multivariable competing risk regression models were performed with the adjustment of all-cause mortality. Secondary analyses examined the effect of increasing duration of GnRHa treatment. Multivariable logistic regression models examined expenditures.Overall, 3295 men with a primary diagnosis of metastatic PCa treated with GnRHa or orchiectomy were identified between years 1995 and 2009, and in adjusted analyses, patients who received a bilateral orchiectomy had significantly lower risks of experiencing any fractures (hazard ratio [HR], 0.77; 95% CI, 0.62-0.94; P = .01), peripheral arterial disease (HR, 0.65; 95% CI, 0.49-0.87; P = .004), and cardiac-related complications (HR, 0.74; 0.58-0.94; P = .01) compared with those treated with GnRHa. No statistically significant difference was noted between orchiectomy and GnRHa for diabetes and cognitive disorders. In individuals treated with GnRHa for 35 months or more, the increased risk for GnRHa compared with orchiectomy was noted for fractures (HR, 1.80), peripheral arterial disease (HR, 2.25), venous thromboembolism (HR, 1.52), cardiac-related complications (HR, 1.69), and diabetes mellitus (HR, 1.88) (P ≤ .01 for all). At 12 months after PCa diagnosis, the median total expenditures was not significantly different between GnRHa and orchiectomy.Gonadotropin-releasing hormone agonist therapy is associated with higher risks of several clinically relevant adverse effects compared with orchiectomy.
Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data
Authors: Riccardo Lencioni, Thierry de Baere, Michael C. Soulen, William S. Rilling, Jean‐Francois H. Geschwind
Journal: Hepatology (2016)

Transarterial chemoembolization (TACE) using lipiodol‐based regimens, including the administration of an anticancer‐in‐oil emulsion followed by embolic agents, is widely used in the treatment of hepatocellular carcinoma (HCC). This approach has been supported by meta‐analyses of randomized, controlled trials (RCTs) performed more than a decade ago. We performed a systematic review to understand current efficacy and safety data of lipiodol TACE in treatment of HCC. A search of the literature published between January 1, 1980 and June 30, 2013 was performed using MEDLINE and EMBASE databases. All potentially relevant publications were reviewed and articles were selected based on predefined inclusion and exclusion criteria. Of a total of 1,564 articles reviewed, 101 articles, including a total of 10,108 patients treated with lipiodol TACE, were selected for the efficacy analysis. Objective response rate was 52.5% (95% confidence interval [CI]: 43.6‐61.5). Overall survival (OS) was 70.3% at 1 year, 51.8% at 2 years, 40.4% at 3 years, and 32.4% at 5 years. Median OS was 19.4 months (95% CI: 16.2‐22.6). A total of 217 articles presenting precise description on numbers of adverse events (AEs) were selected for the safety review: In these studies, a total of 21,461 AEs were reported in 15,351 patients. Liver enzyme abnormalities were the most commonly observed AE, followed by the symptoms associated with postembolization syndrome. Overall mortality rate was 0.6% and the most common cause of death was related to acute liver insufficiency. Conclusions : In a systematic literature review, survival figures of HCC patients undergoing lipiodol TACE appear to be in line with those reported in previous RCTs, and no new or unexpected safety concerns were identified. (H epatology 2016;64:106–116)
Generic immunosuppression in solid organ transplantation: systematic review and meta-analysis
Authors: A. O. Molnar, D. Fergusson, A. K. Tsampalieros, A. Bennett, N. Fergusson, T. Ramsay, G. A. Knoll
Journal: BMJ (2015)

<b>Objective</b> To compare the clinical efficacy and bioequivalence of generic immunosuppressive drugs in patients with solid organ transplants. <b>Design</b> Systematic review and meta-analysis of all studies comparing generic with innovator immunosuppressive drugs. <b>Data sources</b> Medline and Embase from 1980 to September 2014. <b>Review methods</b> A literature search was performed for all studies comparing a generic to an innovator immunosuppressive drug in solid organ transplantation. Two reviewers independently extracted data and assessed quality of studies. Meta-analyses of prespecified outcomes were performed when deemed appropriate. Outcomes included patient survival, allograft survival, acute rejection, adverse events and bioequivalence. <b>Results</b> 1679 citations were screened, of which 50 studies met eligibility criteria (17 randomized trials, 15 non-randomized interventional studies, and 18 observational studies). Generics were compared with Neoral (cyclosporine) (32 studies), Prograf (tacrolimus) (12 studies), and Cellcept (mycophenolate mofetil) (six studies). Pooled analysis of randomized controlled trials in patients with kidney transplants that reported bioequivalence criteria showed that Neoral (two studies) and Prograf (three studies) were not bioequivalent with generic preparations according to criteria of the European Medicines Agency. The single Cellcept trial also did not meet bioequivalence. Acute rejection was rare but did not differ between groups. For Neoral, the pooled Peto odds ratio was 1.23 (95% confidence interval 0.64 to 2.36) for kidney randomized controlled trials and 0.66 (0.40 to 1.08) for observational studies. For kidney observational studies, the pooled Peto odds ratios were 0.98 (0.37 to 2.60) for Prograf and 0.49 (0.09 to 2.56) for Cellcept. Meta-analyses for non-renal solid organ transplants were not performed because of a lack of data.There were insufficient data reported on patient or graft survival. Pooling of results was limited by inconsistent study methods and reporting of outcomes. Many studies did not report standard criteria used to determine bioequivalence. While rates of acute rejection seemed similar and were relatively rare, few studies were designed to properly compare clinical outcomes. Most studies had short follow-up times and included stable patients without a history of rejection. <b>Conclusions</b> High quality data showing bioequivalence and clinical efficacy of generic immunosuppressive drugs in patients with transplants are lacking. Given the serious consequences of rejection and allograft failure, well designed studies on bioequivalence and safety of generic immunosuppression in transplant recipients are needed.
Simulation of survival with first- and second-line non-small cell lung cancer (NSCLC) therapy using a public domain drug-disease modeling framework
Authors: R. Bruno, J. Lu, Y. Sun, L. Claret
Journal: Journal of Clinical Oncology (2009)

8087 Background: Modeling and simulation approaches are advocated to support drug development decisions. In this study, we evaluated the ability of a drug-disease model recently developed by scientists at the FDA using data from pivotal studies in NSCLC (Wang et al. http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008–4351b1–00-index.htm ) to simulate survival and tumor response for approved therapies in NSCLC. Methods: The modeling framework comprises a longitudinal tumor size model and a survival model relating change in tumor size at first visit (week 8) and patient characteristics (tumor size and ECOG performance status at baseline) to survival time. The tumor size and survival models were used to simulate change in tumor size at first visit and expected survival in the carboplatin/paclitaxel (CP) arm of the E4599 study (first-line NSCLC, N Eng J Med. 2006;355:2542–2550) and in the erlotinib arm in the BR.21 study (second-line NSCLC, N Eng J Med. 2005;353:123–132). The predictive distributions (95% prediction interval [PI]) of survival times were derived from multiple replicates (500) of 400 CP patients and 500 erlotinib patients with similar characteristics to patients in the original studies. Results: There was a high level of concordance between the results of the simulation and the observed results in the two arms, indicating that the modeling framework successfully predicted survival and tumor response. Expected median survival was 9.8 (95% PI, 8.2–11.8) months (vs 10.3 months observed) for the CP arm and 6.8 (95% PI, 5.3–8.9) months (vs 6.7 months observed) for the erlotinib arm. The median change in relative tumor size from baseline at week 8 predicted by the model was 12.1% for the CP arm and 9.5% for the erlotinib arm. Conclusions: The modeling framework can be used to perform simulations of survival of approved treatments. These results suggest that the model could be used to simulate survival for investigational treatments based on tumor shrinkage data observed in early clinical studies (e.g. phase II) to support end-of-phase II decisions and the design of phase III studies. [Table: see text]
Overexpression of Wild-Type Retinoic Acid Receptor  (RAR) Recapitulates Retinoic Acid-Sensitive Transformation of Primary Myeloid Progenitors by Acute Promyelocytic Leukemia RAR-Fusion Genes
Authors: Changchun Du, Robert L. Redner, Michael P. Cooke, Catherine Lavau
Journal: Blood (1999)
Randomised Phase Ii Study Evaluating, As First-Line Chemotherapy, Weekly Oral Vinorelbine As a Single-Agent Versus Weekly Paclitaxel As a Single-Agent in Estrogen Receptor Positive, Her2-Negative Patients with Advanced Breast Cancer (Norbreast-231 Trial)
Authors: M. Aapro, E. Staroslawska, S. Morales, M. Ruiz Borrego, S. Cinieri, E. Szombara, L. Garcia Estevez, N. Tubiana-Mathieu, C. Levy, M. Wojtukiewicz, R. Passalacqua, A. Ardizzoia, R. Hegg, L. Fein, H. Simon, E. Richardet, J. Egreteau, O. Garrone, M. Morand, G.R. Villanova
Journal: Annals of Oncology (2014)
Neural Circuitry of Impaired Emotion Regulation in Substance Use Disorders
Authors: Claire E. Wilcox, Jessica M. Pommy, Bryon Adinoff
Journal: American Journal of Psychiatry (2016)

Impaired emotion regulation contributes to the development and severity of substance use disorders (substance disorders). This review summarizes the literature on alterations in emotion regulation neural circuitry in substance disorders, particularly in relation to disorders of negative affect (without substance disorder), and it presents promising areas of future research. Emotion regulation paradigms during functional magnetic resonance imaging are conceptualized into four dimensions: affect intensity and reactivity, affective modulation, cognitive modulation, and behavioral control. The neural circuitry associated with impaired emotion regulation is compared in individuals with and without substance disorders, with a focus on amygdala, insula, and prefrontal cortex activation and their functional and structural connectivity. Hypoactivation of the rostral anterior cingulate cortex/ventromedial prefrontal cortex (rACC/vmPFC) is the most consistent finding across studies, dimensions, and clinical populations (individuals with and without substance disorders). The same pattern is evident for regions in the cognitive control network (anterior cingulate and dorsal and ventrolateral prefrontal cortices) during cognitive modulation and behavioral control. These congruent findings are possibly related to attenuated functional and/or structural connectivity between the amygdala and insula and between the rACC/vmPFC and cognitive control network. Although increased amygdala and insula activation is associated with impaired emotion regulation in individuals without substance disorders, it is not consistently observed in substance disorders. Emotion regulation disturbances in substance disorders may therefore stem from impairments in prefrontal functioning, rather than excessive reactivity to emotional stimuli. Treatments for emotion regulation in individuals without substance disorders that normalize prefrontal functioning may offer greater efficacy for substance disorders than treatments that dampen reactivity.
Intensive induction chemotherapy (API-AI regimen) followed by conservative surgery in adult patients with locally advanced soft tissue sarcoma (STS): Survival is predicted by the histological response
Authors: G. Gomez Abuin, M. Lassalle, S. Bonvalot, P. Terrier, C. Le Pechoux, D. Vanel, C. Robert, M. Saghatchian, P. Berthaud, A. Le Cesne
Journal: Journal of Clinical Oncology (2004)

9036 Background: to determine predictive parameters of response and survival after intensive induction chemotherapy (CT) in patients (pts) with locally advanced high grade STS (LASTS). Methods: from 1996 to 2003, 60 pts (37 m, 23 f) received a CT regimen consisting in 2 cycles of doxorubicin (A) (60 mg/m2 d1 and d15), cisplatinum (100 mg/m2 d1) and ifosfamide (I) 5 g/m2 (d2 and d15). GCSF was added after each course (c) for 6 days, cycle repeated every 4 wks. The median age was 43 yrs (18–68) and the median tumor size was 10 cm (4–25). MRI assessments were performed before CT and surgery (planned at day 65) Results: 222 c of CT were administered (median 4 c/pt). The median DI of AI was 87%. Toxicity (T) was mainly haematological with febrile neutropenia, gde 3/4 neutropenia and thrombocytopenia observed in 46%, 76% and 36% of pts respectively. Two pts had a renale failure and 1 toxic death was observed. Clinical benefit was observed in 56% of pts while 10% of pts progressed clinically during CT. MRI responses (59 evaluable pts) were: 3%CR, 29%PR, 7%MR, 52%SD and 8%PD. All but 2 pts underwent surgery (s): 6 amputations and 52 conservative s (90%). A surgical downstaging was achieved in 13 pts (22%). A good histological response (≥95% necrosis) (GR) was observed in 31% of pts. No correlation was found between histological and clinical response. All but 7 pts (88%) received adjuvant RT. Median follow-up was 39 months (range 2–84). The median time to relapse (5 local and 19 distant relapses) was 19,5 months (0,46–83,5). The 5-yr DFS and OS were 43% [26–59] and 64% [46–81] respectively. GR is the only prognostic predictive factor for DFS (p=0.03) and OS (p=0.04). The 5-yr DFS were 80 % [55–100] and 33 % [14–53] for pts achieving a GR vs poor response respectively. Conclusions: despite haematological T, this induction intensive CT in pts with LASTS allows surgical downstaging and long-term limb salvage. The histological response is a more accurate indicator of chemosensitivity than clinical response and predicts survival in LASTS. No significant financial relationships to disclose.
Temporal and Spatial Distribution of DNA Topoisomerase II Alters During Proliferation, Differentiation, and Apoptosis in HL-60 Cells
Authors: Koichi Sugimoto, Konagi Yamada, Motoki Egashira, Yoshio Yazaki, Hisamaru Hirai, Akihiko Kikuchi, Kazuo Oshimi
Journal: Blood (1998)
Abstract 17195: Association between Reading-to-Reading Blood Pressure Variability and the Severity of Obstructive Sleep Apnea in Patients with Hypertension
Authors: Yongsung Suh, Jong-Chan Youn, Sungha Park, Sang-Hak Lee, Seok-Min Kang, Donghoon Choi, Yangsoo Jang
Journal: Circulation (2012)
Systematic Search for Present and Potential Portals of Entry for Infective Endocarditis
Authors: François Delahaye, Ali M’Hammedi, Brice Guerpillon, Guy de Gevigney, André Boibieux, Olivier Dauwalder, Coralie Bouchiat, François Vandenesch
Journal: Journal of the American College of Cardiology (2016)

Looking for and treating the portal of entry (POE) of infective endocarditis (IE) is important, but published research on this topic is nonexistent.The goal of this study was to systematically search for the POEs of present and potentially new episodes of IEs.Patients were systematically seen by a stomatologist, an ear, nose, and throat specialist, and a urologist; women were systematically seen by a gynecologist; patients were seen by a dermatologist when there were cutaneous and/or mucous lesions. Colonoscopy and gastroscopy were performed if the microorganism came from the gastrointestinal tract in patients ≥50 years of age and in those with familial histories of colonic polyposis. Treatment of the POE was systematically considered.The POEs of the present IE episodes were identified in 74% of the 318 included patients. The most frequent POE was cutaneous (40% of identified POEs). It was mainly (62% of cutaneous POEs) associated with health care and with intravenous drug use. The second most frequent POE was oral or dental (29%). A dental infectious focus was more often involved (59% of oral or dental POEs) than a dental procedure (12%). POEs were gastrointestinal in 23% of patients. Colonic polyps were found in one-half of the patients and colorectal adenocarcinomas in 14%. Performance was good regarding the search for an oral or dental or a colonic potential POE, which were found in 53% and 40% of patients, respectively.Our search for the POEs of present IEs was often successful, as was searching for an oral or dental or a gastrointestinal POE of a new IE episode. We advise the systematic performance of stomatologic examinations in patients with IE and performance of colonoscopy in patients ≥50 years of age or at high risk for colorectal cancer.
Abstract 18633: Prevalemce and Clinical Outcomes of Stent Fracture and Stent Recoil After Drug-eluting Stent Implantation at the Right Coronary Artery Ostial Site at Mid and Late Term
Authors: Masatomo Ozaki, Kazushige Kadota, Tsuyoshi Goto, Satoki Fujii, Hiroyuki Yamamoto, Harumi Kato, Naoki Oka, Yasushi Fuku, Akitoshi Hirono, Takeshi Maruo, Hiroyuki Tanaka, Takeshi Tada, Seiji Habara, Yoshikazu Shigemoto, Daiji Hasegawa, Hiroshi Tasaka, Yoji Okamoto, Suguru Otsuru, Naoki Saito, Yuki Hayakawa, Noriyuki Ohashi, Koshi Miyake, Haruki Eguchi, Mitsuru Yoshino, Yusuke Hyodo, Syunsuke Kubo, Tahei Ichinohe, Hideo Amano, Yu Izawa, Michitaka Nakamura, Kazuaki Mitsudo
Journal: Circulation (2012)

Background: After stent implantation at the right coronary artery (RCA) ostial site, in-stent restenosis (ISR) often occurs and target lesion revascularization (TLR) is required. But at the RCA ostial site, the impact of stent fracture(SF) or stent recoil(SR) on midterm and especially late term restenosis is unknown. Methods: From March 2004 to June 2010, 129 RCA ostial sites were successfully treated with 3 types of drug-eluting stent: sirolimus-eluting stent (SES), n=74; paclitaxel-eluting stent (PES), 39; everolimus-eluting stent (EES), 16. Mid and late term follow-up coronary angiography(CAG) was performed at 8 months and after 20 months. And SF and SR were assessed. We defined SF as apparent strut separation and SR as axial recoil less than 80% in the stent diameter, both analyzed by coronary angiography. Results: We found 41 SF lesions (31.8%) and 24 SR lesions (18.6%) at the 8months follow up CAG. Out of the 102 patients without ISR at the 8months CAG, we were able to follow up 86 patients until the late term. The data of ISR and TLR at 8month and ISR at late term are shown in the table. Conclusion: At the RCA ostial site, SF and SR have an effect on the ISR and TLR at 8month. Furthermore SF and SR have impact on late term ISR consecutively.
Gemcitabine-related thrombocytosis: Does it increase the risk of thrombosis?
Authors: S. Ahmed, R. K. Shahid, A. Sami, S. Yadav, I. Ahmad, D. Mirchandani, D. Popkin, K. Haider
Journal: Journal of Clinical Oncology (2006)

6091 Background: Gemcitabine is an antimetabolite agent that has demonstrated activity in various solid and hematological malignancies. Although thrombocytopenia is a known side effect, gemcitabine-related thrombocytosis has been uncommonly reported. Chemotherapy increases the risk of thrombo-embolism in patients with cancer. The study aimed to identify the incidence of gemcitabine-related thrombocytosis and to determine whether it has been associated with an increased risk of thrombo-embolism. Methods: Medical records of 175 consecutive adults patients with a malignant disease who received gemcitabine at Saskatoon Cancer Center were reviewed. Patients with history of prior thrombo-embolism or with baseline thrombocytosis were excluded. Fisher’s Exact test was done for statistical analysis. Results: 149 eligible patients with median age of 62 (26–83) and M:F of 1.01:1 were identified. 141 (95%) patients had advanced malignancy and 61 (41%) had received prior chemotherapy. 106 (71%) patients received combination of chemotherapy and 95% of those patients received gemcitabine in combination with a platinum compound. Median number of cycle was 3 (1–8). Median platelets count prior to commencement of gemcitabine was 285 × 10 9 (44–449). 83 (56%) patients experienced thrombocytopenia whereas 69 (46%) patients experienced thrombocytosis within 3 weeks of treatment with gemcitabine. Median post-gemcitabine platelet count in patients with thrombocytosis was 622 × 10 9 (457–1385). 15 (10%) patients experienced thrombocytosis with each cycle of gemcitabine. Median duration of thrombocytosis was 2 weeks (0.5−5). 13 (9%) of 149 patients experienced a vascular event (venous, n=9; arterial, n=4) within 6 weeks of treatment with gemcitabine. Median platelet count prior to the vascular event was 268 × 10 9 (79–669). All except one patient had advanced malignancy and 85% had received combination of chemotherapy. 5 of 69 (7%) patients with thrombocytosis experienced a vascular event compared with 8 of 80 (10%) patients without thrombocytosis (p=0.77). Conclusions: Gemcitabine has been associated with an increased incidence of thrombocytosis. However gemcitabine-related thrombocytosis is a transient phenomenon and has not been associated with an increased risk of a vascular event. No significant financial relationships to disclose.