tbuckley/cabot-search huggingface dataset:
Preliminary results of G versus GViElC: A phase III trial of gemcitabine associated to vindesine or gemcitabine alone in elderly or poor performance patients with advanced non-small cell lung cancer (NSCLC)
Authors: A. Santo, G. Genestreti, A. Terzi, P. Azzoni, O. Caffo, E. Galligioni, A. Cipriani, E. Binato, G. Cartei, G. Cetto
Journal: Journal of Clinical Oncology (2006)

17083 Background: Monochemotherapy with gemcitabine (GEM) or vinorelbine is considered the standard treatment in elderly or poor performance (PS) patients (pts) with advanced NSCLC. Many topics report a synergic enhancement of antitumor effect of GEM if associated to Vindesine (VDS). The aim of this study is to evaluate if GEM combined to VDS produces an advantage in terms of overall survival (OS) compared to GEM alone without enhancement of toxicity. Methods: Chemonaive pts with stage IIIB/IV NSCLC, aged ≥ 70 years with PS &lt; 2 or aged &lt; 70 years with PS &gt; 2 were enrolled. Pts were randomized to receive either GEM 1200 mg/m 2 day 1 and 8 every 21 days for three cycles (arm 1) or GEM 1000 mg/m 2 and VDS 3 mg/m 2 (max dose 5 mg) both drugs infused on day 1 and 8 every 21 days for three cycles (arm 2). Pts of both arms received other three cycles in case of responsive or stable disease. Overall survival (OS) was the primary end-point, secondary end-points were time-to-progression and toxicity. First interim analysis was planned at 120 pts enrolled. Results: From May 2002 to December 2005, 107 pts from 13 Italian institutions were enrolled. Their characteristics are: 24 stage IIIB and 83 stage IV, 79 pts with ≥ 70 years (ECOG PS 0–1) and 28 pts with &lt; 70 years (ECOG PS &gt; 2). In arm 1 there were enrolled 55 pts while 52 pts in arm 2: both arms were well balanced with pts characteristics. Conclusions: The enrollment of this phase III trial is ongoing: we are achieving first step for an interim analysis to assess if GEM associated to VDS produces an advantage in terms of OS compared to standard treatment as GEM in monochemotherapy without toxicity enhancement. (Supported by GIVOP: Gruppo Interdisciplinare Veronese di Oncologia Polmonare). No significant financial relationships to disclose.
Treating primary liver cancer with hepatic arterial infusion of floxuridine and dexamethasone: Does the addition of systemic bevacizumab improve results?
Authors: N. E. Kemeny, L. H. Schwartz, M. Gonen, A. C. Yopp, M. I. D'Angelica, Y. Fong, D. Haviland, A. N. Gewirtz, P. J. Allen, W. R. Jarnagin
Journal: Journal of Clinical Oncology (2011)

e14658 Background: Unresectable primary liver cancer (UPLC), including intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC), has poor median survival, typically 10 to 11 months. Hepatic arterial infusion (HAI) has previously shown efficacy, and adding bevacizumab (Bev) may induce changes in the tumor vasculature that improve local delivery of HAI. Methods: Patients with UPLC were treated with HAI of floxuridine (FUDR)/dexamethasone (Dex) administered as 2 week (w) infusion on a 4 w schedule with Bev 5 mg/kg administered IV Q 2w. Response, toxicity and progression-free survival (PFS) were compared to a recent study of HAI without Bev. We hypothesized that adding Bev would result in a 50% improvement in time to progression, which required 48 patients to detect with 90 % power. Results: Twenty-two patients (18 ICC/4 HCC) were treated with HAI FUDR/Dex plus Bev; 7 (31.8%) had partial response and 15 (68.2%) stable disease. Median survival, PFS, and hepatic progression free survival (HPFS) were 31.1, 8.5, and 11.3 months, respectively. In the previous trial (n=34; 26 ICC, 8 HCC) using HAI without Bev, response was 50% and median survivals as listed below. Adding Bev to HAI led to increase in serum bilirubin elevation (>2 mg/dl) in 24% of patients and biliary stent placement in 13.6%, compared to 5.8% and 0% in the first study without Bev. The present study was terminated early due to biliary toxicity. Conclusions: This trial was closed prematurely due to increased biliary toxicity without apparent improvement in outcome (median survival 31.1 and 29.5 months for HAI + Bev versus HAI alone groups). Characteristics HAI FUDR/Dex + Bev (n=22) # (%) HAI FUDR/Dex (n=34) # (%) Bilobar 15 (68%) 24 (71%) Multifocal 15 (68%) 22 (65%) Tumor diameter > 5 cm 17 (77%) 29 (85%) Median albumin 3.2 (2.7-3.9) 3.3 (1.8-4.6) Toxicity Serum bilirubin elevation (>2 mg/dl) 5 (24) 2 (5.8) Biliary stents 3 (13.6) 0 (0) Results Survival 31.1 months (CI 14.1-33.6) 29.5 months (CI 21.3-32.7) PFS 8.5 months (CI 5.5-11.1) 7.3 months (CI 5.3-9.3) HPFS 11.3 months (CI 7.9-15.7) 10.1 months (CI 7.1-12.9)
Correlation of serum leptin level and waist-to-hip ratio (WHR) with overall survival of patients with metastatic breast cancer (MBC) treated with aromatase inhibitors (AIs).
Authors: M. Artac, H. S. Bozcuk, A. Kiyici, O. O. Eren, M. C. Boruban, M. Ozdogan
Journal: Journal of Clinical Oncology (2010)

1106 Background: Aromatase plays a critical role in the estrogen biosynthesis and affects body fat distribution and regulation. Total body aromatization in postmenopausal patients with breast cancer is strongly correlated with plasma leptin levels. Therefore, we aimed to identify whether serum leptin levels and WHR could affect the outcome in MBC patients treated with AIs or not. Methods: A total of 60 metastatic patients with breast cancer treated prospectively with the first-line hormonal therapy were enrolled in this study. Pretreatment body weight, height, WHR, and BMI were recorded. In addition, serum leptin and estradiol levels were measured. Estrogen, progesterone, and c-erb-B2 receptors status were also evaluated in analyses. Univariate and multivariate Cox regression analyses and Kaplan Meier survival curves subjected to log rank testing were utilized to determine the effect of prognosticators and predictors on survival. Forward likelihood ratio was used for the multivariate selection process. A p-value <0.05 was considered to be significant. Results: Median age was 51 years (range 28-75). Median BMI and WHR were found to be 29.3 (range 18-47) and 0.92 (range 0.66-1.20), respectively. Median leptin level was 19,400 pg/ml (1,970-91,900) and estradiol level 29.6 pg/ml (4.0-181.9). There was a positive correlation between leptin levels and WHR (r=0.27, p=0.03) and BMI (r=0.44, p=0.00). Factors associated with the overall survival in the univariate analysis were age and WHR, whereas only WHR retained significance in the multivariate analysis. However, no factor was associated with progression-free survival. However, WHR was found to be a significant prognosticator only if the leptin level was ≥19,400 pg/ml (HR=0.38; 95%CI: 0.16-0.91). Median overall survival figures for patients with leptin levels of ≥19,400 pg/ml and a WHR <0.92 and ≥0.92 were 726 vs. 1,184 days (Log rank statistic=6.51, p=0.01). Conclusions: This study suggests that serum leptin levels and WHR together may serve as potential prognostic markers in patients with metastatic breast cancer treated with AIs. Our results should be validated in a larger cohort of patients. No significant financial relationships to disclose.
A phase II trial of docetaxel (D), estramustine (E) and thalidomide (T) in patients with metastatic androgen-independent prostate cancer (AIPC)
Authors: A. S. Retter, P. M. Arlen, J. L. Gulley, L. L. Latham, S. M. Steinberg, C. C. Chen, E. C. Jones, A. Trout, W. D. Figg, W. L. Dahut
Journal: Journal of Clinical Oncology (2005)

4764 Background: We recently published the results of a randomized phase II trial of D+T vs. D alone. With a median potential follow-up of 46.7 mo., the median OS of D+T was 25.9 mo. and 14.7 mo. with D alone (p=0.04 for the overall difference). We subsequently conducted preclinical evaluations of this and other combinations in a PC3 xenograft prostate cancer model using SCID mice which demonstrated that the combination of D+E+T synergistically and superiorly reduced tumor volume when compared with both D alone and the combination of D+T. This may represent the synergistic effects of joining an active chemotherapy regimen with an antiangiogenic agent. To build upon these findings, we initiated a phase II trial of D+E+T in patients with AIPC. Methods: We have enrolled 12 of a planned 60 patients (pts) using standard phase II eligibility criteria. No prior chemotherapy is allowed. Baseline characteristics include a median age of 70 (55–76), Gleason 8 (6–10), PSA 54 (5–486), Alk Phos 108 (68–336), Hb 12.4 (10.5–13.2). Pts received weekly doses of D (30 mg/m2) and E (420 mg/tid on d1, 280 mg/tid on d2, 3) for 3/4 weeks as well as daily T (200 mg/day (d)). Pts also received enoxaparin (1 mg/kg/d to a max. of 80 mg/d) for thrombosis prophylaxis. Results: 12 of 12 pts (100%) have had PSA declines of > 50%. Of the 7 pts with measurable soft tissue disease, 3 had a PR (43%) and 4 had SD (57%). Toxicities likely related to treatment: 1 Gr 3 fatigue, 1Gr 3 neuropathy and 1 Gr 3 docetaxel infusion reaction. There was no Gr 3 or 4 neutropenia. 2 pts developed Gr 3 or 4 thromboses. 1 had a pulmonary embolus (but had not taken prophylactic enoxaparin consistently) and the 2nd had a DVT. T was discontinued in 5 pts after a median of 3 cycles (range 1–7 cycles) largely due to fatigue or thromboses. E was discontinued in 3 pts. 2 pts have gone off study (one due to toxicity and one due to disease progression). The median number of cycles is 5.5, 10 pts are currently receiving therapy. Conclusions: D+E+T has led to PSA decline of > 50% in all 12 pts enrolled on study. Further accrual is ongoing to better define the response rate and characterize the toxicity of this regimen. No significant financial relationships to disclose.
Factors influencing junior doctors’ choices of future specialty: trends over time and demographics based on results from UK national surveys
Authors: Fay Smith, Trevor W Lambert, Michael J Goldacre
Journal: Journal of the Royal Society of Medicine (2015)

Objective To study trends in factors influencing junior doctors’ choice of future specialty. Design Respondents were asked whether each of 15 factors had a great deal of influence on their career choice, a little influence or no influence on it. Percentages are reported of those who specified that a factor had a great deal of influence on their career choice. Setting UK. Participants A total of 15,765 UK-trained doctors who graduated between 1999 and 2012. Main outcome measures Questions about career choices and factors which may have influenced those choices, in particular comparing doctors who qualified in 2008–2012 with those who qualified in 1999–2002. Results Enthusiasm for and commitment to the specialty was a greater influence on career choice in the 2008–2012 qualifiers (81%) than those of 1999–2002 (64%), as was consideration of their domestic circumstances (43% compared with 20%). Prospects for promotion were less important to recent cohorts (16%) than older cohorts (21%), as were financial prospects (respectively, 10% and 14%). Domestic circumstances and working hours were considered more important, and financial prospects less important, by women than men. Inclination before medical school was rated as important by 41% of doctors who were over 30 years old, compared with 13% of doctors who were under 21, at the time of starting medical school. Conclusions The increasing importance of both domestic circumstances and enthusiasm for their specialty choice in recent cohorts suggest that today’s young doctors prize both work-life balance and personal fulfilment at work more highly than did their predecessors. The differences in motivations of older and younger generations of doctors, men and women, and doctors who start medical school relatively late are worthy of note.
Endothelial chimerism in chronic sclerotic-type chronic graft-versus-host disease (GVHD) and GVHD-associated angiomatosis
Authors: B.H. Kaffenberger, E. Zhang, J.R. Duncan, S. Jaglowski, R.B. Klisovic, S.M. Devine, H.K. Wong, A.A. Gru
Journal: British Journal of Dermatology (2016)

Graft‐versus‐host disease‐associated angiomatosis (GVHD‐AA) is an uncommon manifestation of chronic GVHD consisting of friable vascular proliferations. Using fluorescence in situ hybridization, we demonstrate the presence of donor‐derived endothelial cells within areas of GVHD‐AA. This is the first documented occurrence of a benign neoplastic growth in relationship to a form of chronic GVHD.
Ventilatory efficiency and exercise capacity during exercise in the patients with idiopathic pulmonary fibros
Authors: Jinming Liu, Dandan Huang
Journal: European Respiratory Journal (2014)

OBJECTIVES To study the characteristics of ventilatory efficiency and exercise capacity during Cardiopulmonary Exercise Testing(CPET) in patients with idiopathic pulmonary fibrosis(IPF).  METHODS Pulmonary function test, arterial blood gas analysis and cardiopulmonary exercise testing were performed in 28 cases of patients with idiopathic pulmonary fibrosis from April 2012 to April 2013 and 28 cases of healthy volunteers and measured the relevant parameters.  RESULTS The parameters from pulmonary Function test such as FVC% predicted,FEV1% predicted,MVV % predicted,TLC% predicted,RV% predicte,and DL CO % predicted in the IPF group were significantly lower than those of the control group.The parameters from arterial blood gas analysis, such as PaO 2 ,SaO 2  were lower than those of the control group, thus, P(A-a)O 2  in the IPF group was higher than that in the control group. These results strongly suggestted that IPF group existed restrictive ventilatory dysfunction and impaired gas exchange.The IPF patients had higher VE/VCO 2 -slope( P  2 ( P  2 and VD/VT during every period were significantly higher in IPF group than in the control group( P  P  2 %pred( P= 0.001) were significantly lower in IPF group than in the control group.In IPF group,VE/VCO 2 @AT,VE/VCO 2 -slope,Lowest VE/VCO 2 both had a negative correlation with DLCO%pred and VE/VCO 2 @AT,VE/VCO 2 -slope,LowestVE/VCO 2 both had a negative correlation with peakVO 2 %pred.  CONCLUSIONS With CPET,we find that the ventilation efficiency of the IPF patients were significantly reduced and seriously affecting the patients9 exercise tolerance.
EBUS-TBNA for nodal restaging and relapse in lung cancer
Authors: Markus Enderle, Petra Hoffknecht, Gabriela May, Heiner Schubert, Stefan Rüther, Stefan Fischer, Patrick Zardo, Nicolas Dickgreber
Journal: European Respiratory Journal (2014)

PET-CT and EBUS are current standard procedures for mediastinal lymph node (ln) staging of patients (pat.) with lung cancer (BC). Few publications however focus on restaging and ln recurrence after previous therapy. In this single center retrospective study of a newly established department of respiratory medicine this subgroup is evaluated.

From 08/11 to 01/14 we performed EBUS-TBNA in 25 pat. with BC under suspicion of ln recurrence or for restaging (n=20 NSCLC, n=5 SCLC). Primary staging resulted in UICC 7th edition I/II in n=9 pat. IIIa/b in n=13 and IV in n=3. Diagnostic workup included CT-scan in all pat. and PET-CT in n=20. In 14/25 pat. ln metastases could be confirmed, in 10 pat. by EBUS-TBNA and in 4 pat. by subsequent surgery. 2 of these finally resulted in pN1 and 2 pN2. A further pat. refused further diagnostic but had clinical progressive disease. Pat. with negative EBUS-TBNA result (11/25) received further follow up or continued tumor treatment without developing ln relapase in 6 pat.. In one pat. surgery confirmed pN0 status. Overall EBUS-TBNA had a sensitivity and specificity of 71,4% and 54,5%.

13 of 25 pat. were initially staged UICC IIIa/b. Previous treatment in this subgroup comprised platinum based chemoradiation (n=10), neoadjuvant chemotherapy (n=2) and one resection. 9/13 underwent PET-CT, 5 of these 9 finally showing ln metastases. 2/5 show concordant avid ln in PET-CT. 3/5 showed false negative PET-CT. EBUS diagnosed correctly 4 of 7 finally confirmed malignant ln with a sensitivity and specificity of 57% and 46%. PET-CT shows a sensitivity of 40%.

We consider EBUS-TBNA as a reliable method for confirming malignancy in pat. with known BC. Negative TBNA results however need to undergo surgical workup.
Long-acting anticholinergics in the treatment of severe asthma with irreversible airway obstruction
Authors: Olga Kharevich, Irina Lapteva, Elena Lapteva, Galina Novskaya, Irina Lantukhova, Irina Dovnar, Olga Burak
Journal: European Respiratory Journal (2014)

Introduction. Patients with severe asthma tend to have impaired lung function and irreversible airway obstruction (IAO), which can lead to lower sensitivity of these patients to standard therapy. It is assumed that long-acting anticholinergic drug (tiotropium bromide) can be useful in severe asthma as additional therapy.   The aim  of the study was to evaluate efficacy of tiotropium bromide in patients with severe asthma and IAO.   Methods. The study was held in 19 patients with severe uncontrolled asthma who have been receiving high-dose inhaled corticosteroids in combination with long-acting β 2 -agonists and demonstrated IAO (postbronhodilator FEV 1 /FVC≤70% pred and/or postbronhodilator FEV 1 ≤80% pred). Within this study all patients have been receiving18 μg of tiotropium bromide daily in addition to the current therapy during 12 weeks. The level of asthma control and lung function parameters were assessed initially and after12 weeks of treatment. To compare variables before and after treatment the Wilcoxon test was used. Data are presented as median (range).   Results. After 12 weeks of treatment significant improvement in the level of asthma control (by ACQ-5 from 2.6 (1.4-3.4) to 1.6 (1.0-2.2), p=0.001), increase of postbronhodilator FEV 1  (from 57 (49-66) to 61 (55-79) % pred, p=0.006), and decrease of residual volume (from 185.3 (165.3-250.0) to 168.9 (141.7-189.3) %pred, p=0.046) were revealed.   Conclusion. Thus, addition of tiotropium bromide to standard therapy (high-dose inhaled corticosteroids in combination with long-acting β 2 -agonists) in patients with severe uncontrolled asthma with IAO can improve the level of asthma control and the lung function.
Prognostic value of IGF-1 and IGFBP-3 blood levels in breast cancer
Authors: H. Hartog, H. M. Boezen, M. M. de Jong, M. Schaapveld, J. Wesseling, W. T. van der Graaf
Journal: Journal of Clinical Oncology (2008)

22158 Background: Insulin-like Growth Factor-1 (IGF-1) blood levels are associated with breast cancer (BC) risk in large case-control studies. In addition, one of the major IGF-1 binding proteins, IGFBP-3, has anti-apoptotic properties. We hypothesized that low circulating levels of IGF-1 or high levels of IGFBP-3 may negatively influence tumor progression and prolong overall survival (OS) in BC patients. Methods: IGF-1 and IGFBP-3 levels were measured in blood samples of 535 patients, selected from a cohort study which included 1566 BC patients during 1998–2003. Selection criteria were a diagnosis of resectable local and locally advanced invasive BC and available EDTA sample collected within 6 years post-diagnosis (median 2 y). Records on patient and tumor characteristics were available including a questionnaire on reproductive factors, body mass index (BMI) and alcohol consumption. Mean follow-up was 5.5 years. Associations of available parameters with OS were tested by univariate and multivariate logistic regression analysis. Multivariately significant variables were subsequently entered with IGF-1 and IGFBP-3 in logistic and cox regression analysis. Results: Fourty-six patients (8.6%) died during the follow-up period. There was no association of IGF-1 levels with OS. IGFBP-3 levels were positively correlated with OS (OR 0.72, 95% CI 0.53 - 0.99, p 0.04). Other variables positively associated with OS were radiotherapy and oral contraceptive use (OAC). Tumor size, differentiation grade, age at diagnosis, BMI, and sample interval were negatively associated with OS. In a multivariate model differentiation grade, sample interval and OAC were independent predictors for OS. Addition of IGFBP-3 levels to this model showed no significant independent association of IGFBP-3 with OS. Conclusions: No relation was found between IGF1 blood levels and OS, but IGFBP-3 levels, collected post-diagnosis, were positively correlated with increased OS in BC. Whether preoperative IGFBP-3 levels are also associated with OS is unknown. Interestingly, historical OAC use was independently associated with better OS. Additional studies are needed to confirm and specify these observations. No significant financial relationships to disclose.
IgE and Fcε <scp>RI</scp> are highly expressed on innate cells in psoriasis
Authors: K‐X. Yan, Q. Huang, X. Fang, Z‐H. Zhang, L. Han, K. Gadaldi, K‐F. Kang, Z‐Z. Zheng, J‐H. Xu, N. Yawalkar
Journal: British Journal of Dermatology (2016)

Although elevated serum IgE levels have been reported in psoriasis, the role of IgE in psoriasis still needs to be clarified.To analyse serum total IgE levels in addition to the presence and distribution of IgE and FcεRI in psoriatic lesions, and to investigate alteration of IgE and FcεRI after successful systemic treatment.Total serum IgE levels were determined using enzyme-linked immunosorbent assay. The expression and localization of IgE and FcεRI was investigated using immunohistochemistry and double immunofluorescence.Elevated total serum IgE levels were found in 39% of patients with psoriasis. The levels of total serum IgE were significantly higher in male patients compared with female patients. Furthermore, total serum IgE levels decreased after successful systemic treatment. A positive correlation between IgE+ and FcεRI+ cells and a significant increase of these cells was found in psoriatic lesions when compared with normal skin. Interestingly, IgE+ and FcεRI+ cells decreased significantly after successful therapy with ustekinumab. IgE and FcεRI were coexpressed on mast cells, epidermal Langerhans cells, dermal dendritic cells, macrophages and a small number of neutrophils.IgE might participate in the development of psoriasis by activating FcεRI-bearing cells.
Potential Carcinogens. I. Carcinogenicity of Some Plant Extracts and Their Tannin-Containing Fractions in Rats2
Authors: S. N. Pradhan, E. B. Chung, Bijali Ghosh, B. D. Paul, Govind J. Kapadia
Journal: JNCI Journal of the National Cancer Institute (1974)

NIH Black rats were given ≤75 subcutaneous injections weekly of the total aqueous extracts of Krameria ixina (plant sans root), K. triandra (root), Acacia villosa (root), and Sorghum vulgare (seed); tannin-containing fractions of K. ixina, K. triandra, and A. villosa and a tannin-free fraction of K. ixina were also used. The total extracts and the tannin-containing fractions of K. ixina, K. triandra, and A. villosa produced malignant fibrous histiocytomas after varying numbers of injections. The tannin-free fractions had little carcinogenicity. Generally, the tannin-containing fractions contained most of the carcinogenic material. The materials from A. villosa produced tumors in the shortest time and were the most potent.