tbuckley/cabot-search huggingface dataset:
A randomized phase II study of 500 mg/m<sup>2</sup> and 1,000 mg/m<sup>2</sup> of pemetrexed in patients (pts) with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had prior chemotherapy
Authors: Y. Ichinose, K. Nakagawa, T. Tamura, K. Kubota, N. Yamamoto, S. Adachi, Y. Nambu, Y. Nishiwaki, N. Saijo, M. Fukuoka
Journal: Journal of Clinical Oncology (2007)

7590 Background: Pemetrexed (Pem) 500 mg/m 2 (Pem 500) is currently the standard treatment for pts with locally advanced or metastatic NSCLC who had prior chemotherapy. In a recent Japanese phase I study with full vitamin supplementation, 1,000 mg/m 2 was determined as the recommended dose. This study was to determine if Pem 1,000 mg/m 2 (Pem 1,000) could lead to a better treatment outcome with an acceptable toxicity profile compared with Pem 500 in pts with NSCLC in a 2nd or 3rd line setting. Methods: Pts with PS 0–2, measurable, Stage III/IV NSCLC, who had previously received 1 or 2 chemotherapy regimens, were randomized to receive either Pem 500 or Pem 1,000 on day 1 of a 21-day cycle. The primary endpoint was overall response rate (ORR) based on the RECIST. Secondary endpoints included progression-free survival (PFS), duration of response (DR) and toxicity profile. The planned total sample size for the study was 214 pts. Results: From October 2004 to March 2006, 244 pts were enrolled at 28 centers, 226 pts were randomized and treated, and 216 pts were evaluable for efficacy. Baseline patient characteristics (Pem 500/Pem 1,000: 108/108) were: Males 63%/64%; median age 62/62 years (total range: 26–74); PS 0–1 94%/94%; Stage IV 81%/80%. The median number of treatment cycles completed on both arms was 3 (range 1–20+ for Pem 500 and 1–15+ for Pem 1,000). 11% of the Pem 500 pts and 6% of the Pem 1,000 pts completed at least 10 cycles. ORRs were 18.5% (90% CI: 12.6%-25.8%) for Pem 500 and 14.8% (90% CI: 9.5%- 21.6%) for Pem 1,000, and the respective disease control (PR+SD) rates were 55.6% and 46.3%. Median PFS with Pem 500 and Pem 1,000 was 3.0 and 2.4 months and median DR was 4.7 and 3.8 months, respectively. Grade 4 toxicities observed in more than 1% of pts were neutropenia (3.5% with Pem 500, 3.6% with Pem 1,000) and decreased lymphocyte count (2.6%, 1.8%). One drug related death for interstitial lung disease was reported with Pem 500. Conclusions: Pem 1,000 as well as Pem 500 showed remarkable efficacy outcomes with tolerable toxicity. Since Pem 1,000 showed treatment outcomes similar to Pem 500, this study supports the use of Pem 500 for Japanese pts with NSCLC in a 2nd or 3rd line setting. [Table: see text]
Clinical Trial Designs for Cytostatic Agents: Are New Approaches Needed?
Authors: Edward L. Korn, Susan G. Arbuck, James M. Pluda, Richard Simon, Richard S. Kaplan, Michaele C. Christian
Journal: Journal of Clinical Oncology (2001)

ABSTRACT: Preclinical data suggest that some new anticancer agents directed at novel targets demonstrate tumor growth inhibition but not tumor shrinkage. Such cytostatic agents may offer clinical benefits for patients in the absence of tumor shrinkage. In addition, lower doses of some of these agents may be just as effective as higher doses, implying that toxicity may not be an ideal end point for dose finding. Because of these factors, the sequence and design of traditional phase I, II, and III trials used for cytotoxic agents (which typically shrink tumors and in a dose-dependent manner) may not be appropriate for cytostatic agents. This article discusses options for modifying trial designs to accommodate cytostatic agents. Examples are given where these options have been tried or are currently being tried. Recommendations given for choosing among the trial designs depend on what is known preclinically about the agents (eg, does one have a validated and reproducible biologic end point that can be used to guide a dose escalation?), what is known about the patient population being studied (eg, does one have a well-documented historical progression-free survival rate at 1 year for comparison with the experience of the new agent?), and the numbers of agents and patients available for participation in trials. Planned and ongoing trials will test the utility of some of these new approaches.
Abstract 312: Preprocedural Coronary Computed Tomography Angiography Significantly Enhances Success Rates of PCI in Complex Chronic Total Occlusions
Authors: Andreas Rolf, Gerald S Werner, Johannes Rixe, Martina Werle, Helge Moellmann, Holger M Nef, Constantin Gundermann, Karl-Heinz Tischer, Christian W Hamm, Thorsten Dill
Journal: Circulation (2009)
Risk factors for tuberculosis in patients with early gastric cancer: Is gastrectomy a significant risk factor for tuberculosis?
Authors: Hee Seok Lee, Sung Jin Nam, Young Woo Kim, Il Ju Choi, Bin Hwangbo
Journal: European Respiratory Journal (2012)

Since 1940s, many studies suggested the strong relationship between gastrectomy and the development of TB. But there is no study about the association between TB development and gastrectomy in patients with early gastric cancer (EGC)  We used our EGC cohort confirmed pathologically by gastrectomy (pT1N0M0) or endoscopic mucosal resection (EMR) (pT1) between Jun 2001 and Dec 2008 and followed up with chest X ray over 1year. We searched an active TB case developed at least 3months after gastrectomy and EMR in EGC cohort retrospectively.  Of total 1935 patients with EGC, 1495 patients were classified as gastrectomy cohort and 440 patients as EMR cohort. While only one patient (0.2%) was diagnosed as active TB in EMR cohort, 26 (1.7%) were diagnosed in gastrectomy cohort during the follow-up period. TB cumulative incidence showed significant difference between the two cohort (Log-Rank test P=0.030). Cox proportional multivariate analysis after adjustment with age, sex, and BMI group in EGC cohort showed hazard ratio of old TB lesion was 4.911 (95% CI 2.213-10.901) and that of gastrectomy was 8.599 (95% CI 1.155-64.000). In subgroup analysis using gastrectomy cohort, Cox proportional multivariate analysis after adjustment with age and sex showed hazard ratio of old TB lesion was 4.570 (95% CI 2.041-10.231) and postoperative weight reduction (per 10% compared with weight before gasterectomy) was 2.240 (95% CI 1.452-3.486).  Gastrectomy and old TB lesion on chest radiograph were significant risk factor for TB development in EGC cohort and old TB lesion on chest radiograph and body weight loss after gastrectomy were too in gastrectomy cohort.
GATA-1 blocks IL-6-induced macrophage differentiation and apoptosis through the sustained expression of cyclin D1 and Bcl-2 in a murine myeloid cell line M1
Authors: Hirokazu Tanaka, Itaru Matsumura, Koichi Nakajima, Hanako Daino, Junko Sonoyama, Hitoshi Yoshida, Kenji Oritani, Takashi Machii, Masayuki Yamamoto, Toshio Hirano, Yuzuru Kanakura
Journal: Blood (2000)
Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells
Authors: Heikki Saari, Elisa Lázaro-Ibáñez, Tapani Viitala, Elina Vuorimaa-Laukkanen, Pia Siljander, Marjo Yliperttula
Journal: Journal of Controlled Release (2015)

Extracellular vesicles (EVs) are naturally occurring membrane particles that mediate intercellular communication by delivering molecular information between cells. In this study, we investigated the effectiveness of two different populations of EVs (microvesicle- and exosome-enriched) as carriers of Paclitaxel to autologous prostate cancer cells.EVs were isolated from LNCaP- and PC-3 prostate cancer cell cultures using differential centrifugation and characterized by electron microscopy, nanoparticle tracking analysis, and Western blot. The uptake of microvesicles and exosomes by the autologous prostate cancer cells was assessed by flow cytometry and confocal microscopy. The EVs were loaded with Paclitaxel and the effectiveness of EV-mediated drug delivery was assessed with viability assays. The distribution of EVs and EV-delivered Paclitaxel in cells was inspected by confocal microscopy.Our main finding was that the loading of Paclitaxel to autologous prostate cancer cell-derived EVs increased its cytotoxic effect. This capacity was independent of the EV population and the cell line tested. Although the EVs without the drug increased cancer cell viability, the net effect of enhanced cytotoxicity remained. Both EV populations delivered Paclitaxel to the recipient cells through endocytosis, leading to the release of the drug from within the cells. The removal of EV surface proteins did not affect exosomes, while the drug delivery mediated by microvesicles was partially inhibited.Cancer cell-derived EVs can be used as effective carriers of Paclitaxel to their parental cells, bringing the drug into the cells through an endocytic pathway and increasing its cytotoxicity. However, due to the increased cell viability, the use of cancer cell-derived EVs must be further investigated before any clinical applications can be designed.
Timing and duration of omalizumab response in patients with chronic idiopathic/spontaneous urticaria
Authors: Allen Kaplan, Marta Ferrer, Jonathan A Bernstein, Evgeniya Antonova, Benjamin Trzaskoma, Karina Raimundo, Karin Rosén, Theodore A Omachi, Sam Khalil, James L Zazzali
Journal: Journal of Allergy and Clinical Immunology (2015)

Few data are available that describe response patterns in patients with chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) treated with omalizumab.We sought to describe response patterns by using data from the 3 pivotal omalizumab CIU/CSU trials.Every 4 weeks, randomized patients received dosing with placebo or 75, 150, or 300 mg of omalizumab (ASTERIA I: n = 318, 24 weeks; ASTERIA II: n = 322, 12 weeks) or placebo or 300 mg of omalizumab (GLACIAL: n = 335, 24 weeks). Response was defined as well-controlled urticaria (weekly Urticaria Activity Score [UAS7] ≤ 6) or complete response (UAS7 = 0).Response rates were dose dependent and highest with 300 mg of omalizumab. Some patients responded early (before week 4). At week 12, a higher proportion of patients treated with 300 mg of omalizumab reported a UAS7 ≤ 6 (26.0% [75 mg of omalizumab], 40.0% [150 mg of omalizumab], 51.9% [300 mg of omalizumab], and 11.3% [placebo] for ASTERIA I; 26.8% [75 mg of omalizumab], 42.7% [150 mg of omalizumab], 65.8% [300 mg of omalizumab], and 19.0% [placebo] for ASTERIA II; and 52.4% [300 mg of omalizumab] and 12.0% [placebo] for GLACIAL) or a UAS7 = 0 (11.7% [75 mg of omalizumab], 15.0% [150 mg of omalizumab], 35.8% [300 mg of omalizumab], and 8.8% [placebo] for ASTERIA I; 15.9% [75 mg of omalizumab], 22.0% [150 mg of omalizumab], 44.3% [300 mg of omalizumab], and 5.1% [placebo] for ASTERIA II; and 33.7% [300 mg of omalizumab] and 4.8% [placebo] for GLACIAL). In patients receiving 300 mg of omalizumab with 24 weeks of treatment, median time to achieve a UAS7 ≤ 6 was 6 weeks (ASTERIA I and GLACIAL) and median time to achieve a UAS7 = 0 was 12 or 13 weeks (ASTERIA I and GLACIAL, respectively). Some patients who achieved well-controlled urticaria or complete response sustained response throughout the treatment period.Benefits of omalizumab treatment were evident early (before week 4) in some patients and persisted to week 24. Use of 300 mg of omalizumab demonstrated best results in controlling CIU/CSU symptoms.
An electrodeless, wearable system for simultaneous monitoring of cardiac and respiratory function
Authors: Gaetano Gargiulo, Paul Breen
Journal: European Respiratory Journal (2014)

Introduction:  Complex interactions inextricably link the pulmonary and cardiovascular systems. It is unsurprising then that chronic diseases such as chronic obstructive pulmonary disease (COPD) and heart failure are prevalent comorbidities affecting a huge proportion of the world population. Distinguishing their overlapping physiological effects is difficult. As a result the ability to monitor both cardiac function and respiration in a non-intrusive manner would be of great benefit to clinicians and researchers alike. To address this need, we have developed an inexpensive wearable solution to monitor both cardiac and respiration volume.   Methods:  Four electoresistive bands were pre-calibrated and embedded in a t-shirt. A 1mA constant-current source was applied to each band and the applied voltage recorded at 1kHz using a 16-bit ADC. The circumference of each band was calculated and used to estimate sectional volumes as truncated cones. From this data both respiration and cardiac output in ml are extracted.   Results:  Volume traces clearly display the contribution the top, mid and low sections of the thorax to respiration. Cardiac output volume is also displayed following signal processing to remove the respiration signal.   Conclusions:  This preliminary work demonstrates that an electroresistive system as described has tremendous potential as a low-cost method of recording both respiration and cardiac output.
Training and competing in the heat in youth sports:<i>no sweat</i>?
Authors: M F Bergeron
Journal: British Journal of Sports Medicine (2015)

Good youth sports coaches know well the routine leading up to the early stages of a new season. Assess every child carefully, while identifying and then prioritising the particular gaps and needs, and next outline an approach and plan to effectively advance the process of individual talent and sport development in a positive and enjoyable learning environment, in an effort to make the most of each one's athletic potential and move closer to his or her personal sport aspirations. The coach then begins to work through progressive training and development sessions with each youth athlete and introduces appropriate complementary physical conditioning, while continuing to refine technique and develop viable new competitive tactics. The competition schedule is then carefully planned and the season begins. However, for many young athletes, especially those participating in summer outdoor individual or team sports, environmental heat stress—particularly when the humidity level is high—can have an unanticipated overriding negative impact that can readily undo advances in fitness, movement, speed, power, endurance and competition tactics and goals.

There is widespread recognition of and emphasis (including in the featured consensus statement)1 on the challenges to a young athlete's well-being, safety and sport performance when training and competing in the heat. Moreover, the contributing roles of the environment, acclimatisation status, hydration and other training or competition conditions and scenarios on mitigating or exacerbating exertional heat illness risk have been well clarified. Accordingly, recognised policy statements and guidelines on training and competing in the heat have placed an appropriate emphasis on addressing modifiable factors to meaningfully assist in keeping youth athletes safe and performing well in hot weather.2–4 Yet, undue heat-related problems continue across all sports when youth athletes train and compete in outdoor hot-weather venues. Unfortunately, the response is too often reactionary versus informed anticipation and prevention—that is, …
Towards a better epidemic
Authors: T. Delamothe
Journal: BMJ (2015)

The consensus seems to be that no one had a particularly good Ebola epidemic, with the exception of the charity Medecins Sans Frontieres (MSF). This begs the question of who makes these judgment calls, and what was the last “good” epidemic you can remember?

The World Health Organization got it in the neck for delivering too little, too late, and its own report last week joined in the criticisms, listing lessons learnt and actions planned (doi:10.1136/bmj.h2144). MSF thought the problems went wider than WHO. The international response had been a “global coalition of inaction,” its report concluded (doi:10.1136/bmj.h1619). “For the Ebola outbreak to spiral this far out of control required many institutions to fail,” …
Cryptococcal Meningoencephalitis in a Patient With Multiple Sclerosis Treated With Fingolimod
Authors: Lutz Achtnichts, Otilia Obreja, Anna Conen, Christoph A. Fux, Krassen Nedeltchev
Journal: JAMA Neurology (2015)

1.01 to 1.04; P = .004).The MR analysis showed that shorter TL was causally associated with a higher risk for AD (odds ratio, 1.36 per SD decrease of TL; 95% CI, 1.12 to 1.67; P = .002).Discussion | In the present study, for the first time to our knowledge, we used IV techniques and provided support for a causal effect of TL on the risk for AD using summary GWAS data.The MR analysis has the advantage of being independent of any measured or unmeasured confounders by using genetic variants as IVs.However, an MR study also requires a large sample size to gain sufficient statistical power.To achieve this, we took advantage of the summary GWAS data from the International Genomics of Alzheimer's Project Consortium. 5 Based on the original TL article, 4 we roughly estimate 1 SD decrease to be equal to an attrition rate of 1226 TL base pairs in 40 to 60 years, corresponding to a 36% higher risk for AD.Leukocyte TL, as measured in the GWAS, is correlated with TL in neurons.Thus, it should be considered a proxy of neuronal TL.We tested the MR assumption regarding the pleiotropic effects of the 7 SNPs and did not find any evidence for violations of these assumptions.Additionally, we performed sensitivity analysis by applying likelihood-based methods 6 for the final MR estimate and obtained similar results.In summary, our study provided evidence for a causal relationship between TL and AD.
New medical school to focus on rural practice.
Authors: David Spurgeon
Journal: BMJ (2001)

The Canadian province of Ontario will establish a new medical school—its first in 30 years—with a curriculum focusing on practice in rural and under-serviced areas. With campuses in the northern cities of Sudbury and Thunder Bay, it will begin admitting 55 undergraduates in 2004.

At the same time, the Ontario government announced that it will increase undergraduate and postgraduate enrolment throughout the province by 120 students over the next two years and will increase postgraduate training posts by up to 25 in northern rural communities, beginning in 2002.

The new school is a response to a …
Impacts of multi and specific co-morbidities on the survival of non-surgical non-small cell lung cancer
Authors: Kai Shing Yu, Lap Ah Tse, Ignatius Take-Sun Yu, Martin Chi Sang Wong, Siu-kei Joseph Au, Josette Sin Yee Chor
Journal: European Respiratory Journal (2012)

Background: The prognosis of patients with non surgical non-small cell lung carcinoma (NSCLC) is poor and the presence of co-morbidity may shorten the survival. This study aimed to determine the impacts of multi and specific co-morbidities on the survival of non-surgical NSCLC patients.  Methods: We prospective followed up 603 Chinese patients with newly diagnosed primary NSCLC who were consecutively recruited from a largest oncology center in Hong Kong during 2003-2006 and ineligible for surgery through 31 December, 2008. Multiple Cox9s proportional hazard model was performed to evaluate the impacts of co-morbidity on survival.  Results: The median survival for all patients was 9.30 months (range: 0.17 – 70.6), and the cumulative 2-year survival rate was generally poor (  Conclusion: This study reveals that 9endocrine, nutritional and metabolic disease and immunity disorder9 was the significant risk factor to shorten the survival for non-surgical NSCLC which raises special attention for better supportive or palliative care for lung cancer patients with this type of co-morbidity.
CHEMICAL STUDIES ON INTESTINAL INFANTILISM
Authors: F. H. McCrudden, H. L. Fales
Journal: The Journal of Experimental Medicine (1912)

In three cases of intestinal infantilism, the excretion of nitrogen in the urine per square meter of body surface was low. The heat radiation was normal. In spite of the fact that the absolute quantity of nitrogen was low, the distribution of nitrogen and sulphur among the various nitrogen and sulphur constituents of the urine was in the normal ratio. The ammonia excretion was normal. The ethereal sulphates were slightly increased. The respiratory coefficient showed that the supply of glycogen had not been used up after eighteen hours' starvation.
COPD: Different psychology status (PS) in the patients with different co-morbidity rate
Authors: Kateryna Gashynova
Journal: European Respiratory Journal (2011)

Aim: To evaluate whether and in which extent co-morbidity have influence on the PS in patients with COPD.

Study population: 120 outpatient men with COPD, stage III made the study sample. Exclusion criteria were 1) mental diseases; 2) presence of acute infections.

Methods: For the evaluation of the PS the depression (by Y.Zung scale), the anxiety (by Ch.D. Spilberger questionnaire) and the vegetative lability (by VELA test) were studied in all patients. Co-morbidity rate was established during analysis of patient's medical documentation.

Results: In accordance with co-morbidity rate all patients were divided on three groups (GR): GR I without any co-morbid condition, GR II –with 1-2 and GR III – with more than 3 co-morbid conditions. All groups were similar regarding to age and smoking status. One or more abnormalities in PS were found in 2 (10.53%) patients of Group I, in 63 (74.11%) – of Group II and 13 (81.25%) persons in Group III. The data of psychological tests are performed in the table 1.

View this table:



Conclusions: Co-morbid condition significantly impair psychology status in patients with COPD, and the most significant changes concerns depression, personal anxiety and vegetative lability level.
Abstract 16807: New Approach to Pressure-Volume Loop Analysis Using Custom Made High Fidelity MRI Compatible Pressure Sensor Tipped Catheters and Real Time MRI
Authors: Yoav Dori, Menekhem Zviman, Frank Miller, Henry Halperin, Jonathan J Rome
Journal: Circulation (2011)

Background: Pressure-Volume (PV) loop analysis remains the only load-independent method to assess cardiac function. However, current methods limit the clinical use of PV loops particularly in congenital defects. We developed a novel technique for PV loop analysis using custom made high fidelity MRI compatible pressure sensor tipped catheters (hfMRIc) with real time MRI (rtMRI). Hypothesis: Accurate PV loop cardiac function can be obtained using single plane rtMRI imaging and hfMRIc pressure sensor tipped catheters. Methods: PV loop analysis was performed in the LV of 4 swine. Instantaneous ventricular volume estimation was obtained with the Simpson method using V = ∑Vi(Li) where Vi(Li) are length volume relations derived from a short axis cine stack and a LA cine plane and Li are lengths obtained using custom made segmentation software and a single rtMRI LA plane (Figure 1(a)). Volume error calculations were performed at two different preload conditions. Pressure measurements were obtained with custom made hfMRIc fiber optic pressure sensor tipped catheters. Pressure measurements were compared to values obtained with a high fidelity Millar catheter positioned in the Aorta. Results: At a sampling rate of 20 Khz, the pressure difference between the hfMRIc catheters and the Millar catheter was 1% with a standard deviation (SD) of 0.9%. There was no effect of MRI scanning on pressure recording. The difference between the volume measured with a short axis cine stack and the volume estimated with our methodology using a single LA cine plane was 6.7% with a SD of 4.7%. EDPVR and ESPVR and instantaneous PV loops were obtained by inflating a balloon in the IVC while obtaining rtMRI planes at a temporal resolution of 42 msec (Figure 1(b)). Conclusions: Using this new technique, we can accurately assess the instantaneous cardiac function using PV loops. Unlike current technology this new modality is not dependent on ventricular shape or valve function.