tbuckley/cabot-search huggingface dataset:
Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients.
Authors: G Todeschini, A Ambrosetti, V Meneghini, G Pizzolo, F Menestrina, M Chilosi, F Benedetti, D Veneri, G L Cetto, G Perona
Journal: Journal of Clinical Oncology (1990)

We report the clinical findings of 21 consecutive patients affected by mediastinal large B-cell lymphoma with sclerosis. This type of lymphoma is a recently described histopathologic entity characterized on clinical grounds by distinctive features, which, according to our series, can be summarized as follows: young age (median, 30 years; range, 15 to 42 years), prevalence of females over males (15 v six), rare occurrence of superficial lymph node enlargement (three of 21 patients), and involvement of unusual extranodal sites (kidney six, adrenal cortex two patients). The clinical course appears to be closely related to treatment. In fact, complete remission (CR) was not obtained in the six patients submitted to conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus bleomycin (CHOP-Bleo) regimens until 1985, as opposed to 13 CRs reached in the 15 patients subsequently treated with more aggressive regimens after 1985 (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B], 12 patients; methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone [M-BACOD], two patients; and vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate, and prednisone [F-MACHOP], one patient; plus involved-field radiotherapy, 10 patients). Among the 13 patients who achieved a CR, only one relapse was observed at 10 months. The median overall survival of complete responders after an observation period of 11 to 69 months has not yet been reached, and the event-free survival curve indicates that 90% of patients who achieve CR may be potentially cured.
Abstract 10642: Small Conductance Calcium Activated Potassium Channels as a New Atrial Fibrillation Target
Authors: XiaoYan Qi, Jonas G Diness, Bianca Brundel, Patrice Naud, Chia-Tung Wu, Masahide Harada, Morten Grunnet, Stanley Nattel
Journal: Circulation (2012)

Background: Recently, single nucleotide polymorphisms (SNPs) in Ca2+-dependent K+-channels (encoded by SK (KCa2.x) subunits) have been implicated in atrial fibrillation (AF) risk. Here, we assessed...
Treatment for superior sulcus tumors (SST): Effect of surgery first followed by adjunct concurrent chemoradiotherapy on survival of patients with marginally resectable SST.
Authors: R. Komaki, X. Wei, P. Allen, J. A. Roth, S. Swisher, D. C. Rice, G. L. Walsh, F. V. Fossella, J. J. Erasmus, J. D. Cox
Journal: Journal of Clinical Oncology (2010)

7026 Background: The role of preoperative treatment for locally advanced SST (LA-SST) has not been well defined. We compared two IRB-prospective phase II trials of patients (pts) with LA-SST (T3-4 N0-3 M0) treated at The University of Texas M.D. Anderson Cancer Center. Methods: Trial A (16 pts, 1988 to 1997) was induction chemotherapy consisting of cyclophosphamide (500 mg/m2 i.v.), VP-16 (100 mg /m2 i.v.) and cisplatin (80 mg/m2 i.v.)×2-3 cycles followed by en bloc resection, then post operative radiotherapy (RT) with 60-66Gy/30-33 Fx depending on the surgical margin. Trial B (32 pts, 1992 to 2007) was immediate en bloc resection followed by concurrent chemoradiotherapy (CCRT). The RT was 1.2 Gy/Fx, bid, with 60 Gy/50 Fx or 64.8 Gy/54 Fx depending the surgical margin status. Concurrent chemotherapy consisted of cisplatin (50 mg/m2 i.v.) and VP-16 50 mg, p.o. given on the day 1 and 8 RT, repeated every 29 days ×4 cycles. Results: Median follow-up was 41 months (range, 2-155 months). Median age was 55 (range, 34-69 years). The AJCC 6th clinical stage was 27 stage IIB, 5 stage IIIA and 16 IIIB pts. Six percent (1/16) of pts had KPS less than 90 in trial A compared to 50% in trial B (16/32; p=0.003). All other patient factors including ethnicity, gender, tumor histology, baseline weight loss, clinical stage, and total RT treatment dose were evenly distributed between the two trials. Median overall survival (OS) was 18.6 months and 112.2 months for trial A and B respectively (p=0.0005). The 5-year OS fractions for trial A and B was 18.8% and 53.1% (p=0.0005); 5-year local-regional control was 60.0% and 88.8% (p=0.02); distant metastasis-free survival was 36.7% and 58.1% (p=0.06); and disease-free survival was 26.7% and 54.9, respectively (p=0.02). Conclusions: This study suggests that immediate surgery followed by CCRT significantly improved survival and recurrence rate compared to pre-operative induction chemotherapy followed by surgery and RT in pts with marginally resectable LA-SST. No significant financial relationships to disclose.
A phase I study of two different schedules of nab-paclitaxel (Nab-p) with ascending doses of vandetanib (V) in patients (pts) with advanced solid tumors.
Authors: A. B. El-Khoueiry, S. Iqbal, H. Lenz, L. Roman, B. J. Gitlitz, D. Yang, S. Cole, J. Shriki, C. Hughlett, A. Garcia
Journal: Journal of Clinical Oncology (2010)

3059 Background: Nab-p is an albumin bound paclitaxel. V is a potent inhibitor of VEGFR 2 and EGFR. Preclinical data reveal enhanced Nab-p activity with concurrent VEGF inhibition. Primary objective was to determine the maximum tolerated dose (MTD). Methods: Pts were randomized to one of 2 cohorts. Dose of Nab-p was fixed (Cohort A: Nab-p 100 mg/m2 IV weekly for 3 wks q 28 days; Cohort B: Nab-p 260 mg/m2 IV q 3 wks) while 3 doses of V were evaluated in both cohorts (100 mg, 200 mg, 300 mg PO daily). A standard 3+3 design was used. Expansion at the MTD was planned for both cohorts. Results: 46 pts were treated: 21 (cohort A), 13 (cohort B), 12 (cohort B expansion). Median age 56 (range 26-81), Karnofsky PS 100% (6), 90% (21), 80% (17), <70% (2). 17 males, 29 females. Median number of prior treatments 2 (range 1-7). Most common disease sites: pancreatic 15 (33%), ovarian 8 (17%), gastric 7 (15%), endometrial 3 (6%), lung 3 (6%). There was one DLT at each dose level in cohort A (grade 3 rash in 2 pts, grade 4 neutropenia in 1 pt). No DLTs in cohort B. MTD was Nab-p 100 mg/m2 IV weekly for 3/4 wks and V 300 mg daily in cohort A; Nab-p 260 mg/m2 IV q 3 wks and V 300 mg daily in cohort B. No grade 4 toxicities in cycle 1. Toxicities in all cycles were comparable to those in cycle 1 and will be reported at the time of presentation. 4 pts (3 with pancreatic ca and 1 with unknown primary ca) had a PR; 24 pts had SD (pancreatic 8, ovarian 7, prostate 2, lung 2, other 5). The median duration of SD was 5.7 mo (95% CI: 3.9-6.7). Conclusions: Both schedules of Nab-p with V are safe and well tolerated. The MTD for both cohorts was the maximum planned dose. Accrual to the expansion phase at the MTD in cohort A is ongoing and restricted to pts with advanced pancreatic cancer. Exploratory analysis of SPARC genomic polymorphisms as potential markers of efficacy is in progress. Cycle 1 grade 3 toxicities (other than DLT) Cohort A (n= 21) Cohort B dose escalation + expansion (n= 25) Neutropenia 19% 12% Nausea 5% — Vomiting 5% — Mucositis 5% — Hypertension 10% 8% Prolonged QT (asymptomatic) 5% 8% Arthralgia — 4% Diarrhea — 4% Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca Abraxis BioScience, AstraZeneca
Survival and cost-effectiveness of docetaxel (D) and paclitaxel (P) in patients with metastatic breast cancer (MBC): A population-based evaluation
Authors: T. T. Vu, S. Ellard, I. Olivotto, S. C. Taylor, M. L. De Lemos, C. Speers, K. Kuik, F. Hu
Journal: Journal of Clinical Oncology (2006)

6117 Background: A randomized comparison between P and D for MBC reported that overall survival (OS) was significantly superior for D (Ravdin, et al). We report a population-based comparison of P (3-hour infusion) to D (1-hour infusion) in MBC patients with prior exposure to anthracycline in terms of OS and cost-effectiveness (CE). Methods: Data on MBC patients treated with single-agent P or D (January 1999 - December 2002) were retrospectively reviewed. OS, defined as time from initiation of taxane to death from any cause, was compared using a 2-tailed log-rank test and expressed as Kaplan-Meier plots. A CE analysis, including cost of drug (list price $CDN), labour and supplies, was performed using median cost/patient and median OS (MOS). Incremental CE ratios (ICERs) were compared in a sensitivity analysis varying MOS to the extremes of the 95% confidence interval (95% CI). Results: 435 patients met eligibility criteria. MBC prognostic factors were balanced between D and P groups ( table ). MOS was significantly longer for D vs. P. (10.9 vs. 8.3 months; HR 0.76; 95% CI, 0.62 to 0.92; P = 0.006). The median number of cycles administered were 4 (D) and 3 (P). The respective cost/month of MOS is $805 (D) and $303 (P). The ICER of D vs. P was $2,434/month MOS gained. The range of ICERs in the sensitivity analysis was $1,121 to 7,361/month MOS gained. These results were robust except that P dominates when the low end of the 95%CI of MOS for D is compared to the high end for P. Conclusion: This population-based study corroborates the randomized trial’s conclusion that for patients with metastatic breast cancer, D provided superior survival compared to P. Each additional month of survival had an incremental cost of $2,434. [Table: see text] [Table: see text]
The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation
Authors: Wook-Jin Chae, Allison K. Ehrlich, Pamela Y. Chan, Alexandra M. Teixeira, Octavian Henegariu, Liming Hao, Jae Hun Shin, Jong-Hyun Park, Wai Ho Tang, Sang-Taek Kim, Stephen E. Maher, Karen Goldsmith-Pestana, Peiying Shan, John Hwa, Patty J. Lee, Diane S. Krause, Carla V. Rothlin, Diane McMahon-Pratt, Alfred L.M. Bothwell
Journal: Immunity (2016)
Prevalence of alpha-1 antitrypsin deficiency (AATD) and frequencies of alleles PI*S and PI*Z in patients with COPD in Brazil
Authors: Rodrigo Russo, Laura Zillmer, Oliver Nascimento, Gildo Francisco Santos, Leandro Fritscher, Marc Miravitlles, Fernando Lundgren, Marcela Amorim Alves, Heicilany Del Carlos Gondim, Maria Penha Uchoa Sales, Maria Vera Cruz Oliveira, Altay A.L. Souza, José Roberto Jardim
Journal: European Respiratory Journal (2013)

Introduction: AATD affects about one in 2000–5000 individuals. According to PLATINO study, there are 5 to 7 million patients with COPD in Brazil, however there is no epidemiological data on the prevalence of AATD or the frequency of occurrence of deficiency alleles among them.

Objective : to estimate the prevalence of AATD in patients with COPD in Brazil and the frequency of occurrence of deficiency alleles.

Methods: dried blood spot (DBS) samples were tested for ATT in 1019 patients with COPD in five Brazilian cities. Eluated was prepared from DBS 6mm diameter perforated discs (WhatmanTM, GE, 903, lot W101, USA) and 200 μmL phosphate-buffered saline (pH 7.4) overnight at 4° C. All individuals with DBS dosage less than 2.64 mg/dl (upper limit of the confidence interval of the cutoff point) were considered as possible disabled and an AAT serum dosage was performed. All individuals with a serum dosage <113 mg/dl had a genotyping performed. Serum and DBS samples were determined using the rate immune nephelometric method (Siemens, BNII).

Results: 99 patients had a DBS dosage equal or less than 2.64 mg/dl and 26 of them a serum dosage <113 mg/dl. The prevalence of AATD in patients with COPD was 2.55%. Frequency of the main deficiency phenotypes were: PiMZ (1.17%), PiZZ (0.78%), PiMS (0.40%), PiSS (0.1%), and PiSZ (0.1%).

Conclusion: this is the first study designed to establish the prevalence of AATD and frequency of deficiency alleles in patients with COPD in Brazil. The prevalence of 2.55% reflects the rates found in studies around the world and reinforces the need for screening all patients with COPD followed by genotyping patients with AATD.
Goserelin plus anastrozole in the treatment of premenopausal hormone receptor positive, recurrent or metastatic breast cancer
Authors: R. W. Carlson, C. M. Schurman, E. Rivera, C. T. Chung, S. C. Phan, E. K. Dice, E. Thomas, V. Valero
Journal: Journal of Clinical Oncology (2007)

1030 Background: Aromatase inhibitors (AIs) are highly active in postmenopausal women with hormone receptor positive breast cancer. However, the AIs do not suppress ovarian estrogen synthesis and are not effective in premenopausal women. This phase II study was initiated to estimate the activity of anastrozole when given with ovarian suppression by goserelin in premenopausal women with ER and/or PgR positive metastatic breast cancer. Methods: Premenopausal women with measurable recurrent or metastatic, ER and/or PgR positive breast cancer; no prior AI or LH-RH agonist/antagonist; no adjuvant chemotherapy within 6 months; ECOG performance status of 0–2; adequate organ function; and who provided signed, informed consent were eligible. A 2 stage phase II design was utilized. Treatment was with goserelin 3.6 mg SQ q4wk and anastrozole 1 mg/day begun on day 22 of protocol treatment. Treatment was continued to disease progression. Results: 35 patients (pts) were enrolled. Three were excluded from analysis for the following: 1 postmenopausal, 1 consent withdrawal, 1 early oophorectomy. Of the remaining 32 pts, median age was 43 yrs (range 26–51 yrs), 18 (56%) had prior chemotherapy, and 9 (28%) had prior SERM. Pts were Asian/Middle Eastern 22%, Caucasian 62%, Black 13%, Hispanic 3%. Disease sites were lymph node 50%, breast 44%, bone 81%, lung 41%, liver 22%, pleural effusion 6% and soft tissue 6%. Receptor status was ER+/PgR+ 75%, ER+/PgR- 22% and ER-/PgR+ 3%. Response: Treatment resulted in complete response (CR) in 1(3%), partial response (PR) in 11(34%), stable disease 6+ mos (SD) in 11(34%), and clinical benefit (CR+PR+SD) 23 (72%). Median TTP was 8 mos (range 2 - 63+ mos); median OS was 26 mos (range 11 - 63+ mos). Estradiol levels were detectable in 30/31 pts at baseline (median 56 pg/ml, range &lt;10 - 273 pg/ml). Mean estradiol levels (pg/ml) were 75 at baseline, 21 at 1 mos, 19 at 3 mos, and 15 at 6 mos. TOXICITY: One grade 3 weight loss. All other toxicities were grade 1–2. Conclusions: Ovarian suppression with goserelin in combination with anastrozole is well tolerated and highly active in the treatment of premenopausal, hormone receptor-positive metastatic breast cancer. Support provided by AstraZeneca Pharmaceuticals No significant financial relationships to disclose.
Microbial aetiology, outcomes, and costs of hospitalisation for community-acquired pneumonia
Authors: Simone Spoorenberg, Willem Jan Bos, Rik Heijligenberg, Paul Voorn, Jan Grutters, Ger Rijkers, Ewoudt Van de Garde
Journal: European Respiratory Journal (2014)

Introduction: Community-acquired pneumonia (CAP) carries a high burden worldwide, in particular in the elderly. Of all CAP episodes in elderly 20-40% are treated in-hospital. This results in considerable health care costs. Knowledge on exact costs of CAP is indispensable to estimate cost-effectiveness of new strategies aiming to prevent and/or improve clinical outcome of CAP.

Aim: To investigate clinical outcome and especially costs of hospitalisation in CAP in relation to microbial aetiology.

Methods: An observational analysis in a cohort of 505 patients hospitalised with confirmed CAP between 2004 and 2010 was performed.

Results: Streptococcus pneumoniae was the most identified causative pathogen (25%), followed by Coxiella burnetii (6%) and Haemophilus influenzae (5%). Overall median length of hospital stay was 8.5 days, in-hospital mortality rate was 4.8%. Total median hospital costs per patient were €3,899 (IQR 2,911-5,684). General ward nursing costs represented the largest share (57%), followed by nursing on the intensive care unit (16%) and diagnostic microbiological tests (9%). In multivariate regression analysis, Pneumonia Severity Index class IV-V, Staphylococcus aureus , and Streptococcus pneumonia as causative pathogen, were independent cost driving factors. Coxiella burnetii was a cost-limiting factor.

Conclusion: Costs of hospitalisation for CAP are mainly caused by nursing costs, and increased disease severity and S. pneumoniae and Staphylococcus aureus as causative pathogens are independent cost driving factors. This suggests to focus further research on low-cost interventions aimed at reducing length of hospital stay and prevention of CAP caused by these pathogens.
Variants near the HLA complex group 22 gene (HCG22) confer increased susceptibility to late-onset asthma in Japanese populations
Authors: Yohei Yatagai, Tomomitsu Hirota, Tohru Sakamoto, Hideyasu Yamada, Hironori Masuko, Yoshiko Kaneko, Hiroaki Iijima, Takashi Naito, Emiko Noguchi, Mayumi Tamari, Michiaki Kubo, Atsushi Takahashi, Satoshi Konno, Hironi Makita, Masaharu Nishimura, Minako Hijikata, Naoto Keicho, Sakae Homma, Yoshio Taguchi, Arata Azuma, Shoji Kudoh, Nobuyuki Hizawa
Journal: Journal of Allergy and Clinical Immunology (2016)
A Specific Mapping Study Using Fluorescence Sentinel Lymph Node Detection in Patients with Intermediate- and High-risk Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection
Authors: Daniel P. Nguyen, Philipp M. Huber, Tobias A. Metzger, Vera Genitsch, Hans H. Schudel, George N. Thalmann
Journal: European Urology (2016)
Chromosome Aberrations Acquired In Vitro by Human B-Cell Lines. II. Distribution of Break Points
Authors: M Shade, M A Woodward, C M Steel
Journal: JNCI Journal of the National Cancer Institute (1980)

Among 165 human B-cell lines examined, 57 were found to have karyotypic abnormalities that involved chromosome breakage. The sites of breakage were identified with quinacrine-, Giemsa-, and reverse-banding techniques, and the distribution of 239 break points was plotted. A pronounced excess of telomeric and, to a lesser extent, centromeric breaks was observed. Chromosomes No. 7, 8, 9, 11, and 14 were involved in structural rearrangements more often and chromosomes No. 2, 5, 10, 20, and X less often than was predicted on the basis of their relative lengths. Lines derived from patients with different categories of disorders varied in the distribution of break points throughout the karyotype. In this sample of cell lines, No. 8q; 14q translocations were found only in cultures derived from patients with Burkitt's lymphoma and were never observed to arise among other Epstein-Barr virus-carrying lines even after several hundred cell generations in vitro. An additional feature, which was evidently restricted to lines derived from leukemia or lymphoma patients, was the presence of interstitial insertion, deletion, or reduplication, particularly involving the long arm of chromosome No. 1.
Abstract 15306: Detection of Left Ventricular Diastolic Dysfunction Using P Wave Morphology on Electrocardiography
Authors: Katsuomi Iwakura, Atsunori Okamura, Yasushi Koyama, Motoo Date, Koichi Inoue, Hiroyuki Nagai, Yuko Toyoshima, Koji Tanaka, Toshinari Onishi, Yohei Sotomi, Akinori Sumiyoshi, Yoichi Nozato, Nobuaki Tanaka, Kohei Azuma, Yoshiyuki Orihara, Yuko Yamanaka, Takafumi Oka, Tomohiro Yamasaki, Satoshi Kameda, Kenshi Fujii
Journal: Circulation (2013)

Background: Left ventricular (LV) diastolic dysfunction could determine exercise capacity and is relevant to prognosis of patients with heart failure. Assessment of its presence is critical for the...
Abstract 13780: JNK Inhibition Mimics the Beneficial Effect of Roux-en-Y Gastric Bypass Surgery on Obesity-Induced Endothelial Dysfunction
Authors: Petia Doytcheva, Elena Osto, Thomas Baechler, Marco Bueter, Christian M Matter, Thomas A Lutz, Thomas F Luscher
Journal: Circulation (2014)

Introduction: Roux-en-Y gastric bypass surgery (RYGB) reduces weight and long-term cardiovascular risk in obese patients. We previously demonstrated that in diet-induced obese rats RYGB improves aortic endothelial vasorelaxation 8 days after surgery in a weight loss-independent manner. Improved endothelial function was associated with decreased JNK phosphorylation and increased Akt and eNOS phosphorylation in the aorta. Hypothesis: We investigated whether in vivo inhibition of JNK activity in sham-operated ad libitum-fed rats mimics these endothelial effects of RYGB. Methods: Male Wistar rats were fed a high fat (60%) high cholesterol (1.25%) diet for 7 weeks before undergoing either RYGB or sham surgery; sham-operated rats received vehicle (sham_AL) or the JNK-specific inhibitor SP600125 40mg/kg/day s.c. for 8 days post-surgery (sham_SP). Then, thoracic aortic rings were isolated and subjected to ex vivo isometric tension recordings. After submaximal contraction with norepinephrine (10-6mol/L), cumulative relaxation responses were performed to GLP-1 (7-36) amide (10-12 to 10-6mol/L) or insulin (10-12 to 10-5mol/L); tests were repeated after preincubation with the eNOS inhibitor L-NAME (10-4mol/L). Western blot analysis of JNK, Akt and eNOS was also performed on aortic tissue lysates. Results: Body weight did not differ between sham_SP and sham_AL rats, while the weight loss of RYGB rats was significant 8 days after surgery. GLP-1- and insulin-induced vasorelaxation responses improved in RYGB compared to sham_AL rats; interestingly, sham_SP rats had endothelial relaxation similar to RYGB rats. All responses were blocked by preincubation with L-NAME, suggesting an eNOS-dependent effect. JNK protein phosphorylation in aortic lysates was decreased in RYGB and sham_SP rats compared to sham_AL, while Akt phosphorylation was increased. eNOS phosphorylation and dimerization were also increased in RYGB and sham_SP compared to sham_AL rats. Conclusion: JNK inhibition seems to mimic the immediate eNOS-mediated endothelial protective effects of RYGB. Further, our study underlines a crucial role of JNK in obesity-associated endothelial dysfunction, suggesting a novel mechanism for the cardiovascular effects of RYGB.