tbuckley/cabot-search huggingface dataset:
Occam's razor or Hickam's dictum? Allergic bronchopulmonary aspergillosis and eosinophilic granulomatosis with polyangiitis*
Authors: Scott R Henderson, Anand Shah, Susan J Copley, H Terence Cook, CD Pusey, Alan D Salama, Philip W Ind
Journal: Thorax (2015)

Occam's razor, named after William of Ockham a Franciscan friar of the early 14th century, refers to the principle of logic that states that the simplest explanation is the most likely correct; in science with competing hypotheses, the one with the fewest assumptions is preferred.Hickam's dictum is the counter-argument to Occam's razor in medicine; the statement 'Patients can have as many diseases as they damn well please' attributed to John Hickam, a great US physician and educator, who originally published research on lung function in heart and lung disease.
VEGF receptor expression on reactive breast cancer stroma: paving the way for tumor invasion
Authors: A. T. Hooper, G. Akiri, D. Jin, S. V. Shmelkov, E. Chuang, S. J. Shin, Y. Wu, D. J. Hicklin, S. Rafii, L. T. Vahdat
Journal: Journal of Clinical Oncology (2005)

9642 Background: Stromal cells, along with the extracellular matrix (ECM), provide the microenvironment necessary for growth, survival, invasion and ultimately metastasis of primary tumors. Infiltrating breast carcinomas characteristically elicit a reactive stromal response, consisting of changes in ECM and stromal cell phenotype. The appearance of reactive stroma, including tumor associated fibroblasts (TAFs), can accompany or precede the malignant transformation of epithelial cells and has been reported to support tumor progression. Moreover, cytokines have been shown to play a critical role in the regulation of the tumor microenvironment. VEGF-A is a multifunctional angiogenic factor which was previously linked to tumor progression. VEGF-A exerts its effects via VEGFR-1 (FLT-1) and VEGFR-2 (KDR) tyrosine kinase receptors. We aim to examine the expression of VEGFR-1 and VEGFR-2 on reactive tumor stroma in breast carcinomas. Methods: A panel of breast carcinomas was examined for VEGFR-1 and VEGFR-2 expression via immunohistochemical staining of tissue sections and in vitro cultures of TAFs. Results: Immunostaining demonstrated that VEGFR-1 is expressed on malignant stromal cells, including TAFs, endothelium and smooth muscle. VEGFR-1 expression is predominantly localized to the invasive, inflammatory, angiogenic edge in several aggressive tumors. VEGFR-2 expression was restricted to endothelium but was upregulated in the reactive stroma. When breast cancer stromal cells were cultured in vitro, VEGFR-1 was expressed on the stromal fibroblasts and VEGFR-2 expression was localized to the endothelium, further supporting aforementioned data. Conclusions: Our results demonstrate that VEGF receptor expression on reactive tumor stroma might be important for breast carcinoma advancement via the establishment of a self-contained niche that supports tumor progression and invasion. Current studies are examining whether VEGF-A signaling through VEGFR-1 can promote tumor progression, and if blocking VEGFR-1 signaling on malignant stroma can inhibit tumor growth. Therefore, therapeutic inhibition of VEGFR-1 may provide a novel strategy to target breast carcinoma. No significant financial relationships to disclose.
The Effectiveness of Multiple Electrode Radiofrequency Ablation in Patients with Hepatocellular Carcinoma with Lesions More than 3 cm in Size and Barcelona Clinic Liver Cancer Stage A to B2
Authors: Chen-Chun Lin, Ya-Ting Cheng, Wei-Ting Chen M, Shi-Ming Lin
Journal: Liver Cancer (2015)

Outcomes of hepatocellular carcinoma (HCC) lesions >3.0 cm in size including Barcelona Clinic Liver Cancer (BCLC) stage B after radiofrequency ablation (RFA) with a single electrode remain unsatisfactory. This study aimed to investigate the outcomes of RFA with multiple electrodes (ME-RFA) for HCC tumors 3.1-7.0 cm in size and BCLC stage B. This retrospective study included 70 consecutive patients with 58 medium- (3.1-5.0 cm) and 17 large- (5.1-7.0 cm) sized HCCs after ME-RFA using a controller. Outcomes in terms of complete response, primary technique effectiveness, local tumor progression, and overall survival were investigated. After 1-4 applications of ME-RFA, the rates of complete response and PTE in medium-sized tumors were 79.3% and 91.4%, respectively, and in large tumors were 76.5% and 94.1%, respectively. Overall, the major complication rate was 5.7%. After a median 21-month follow-up period, both two- and three-year estimated overall survival rates were above 80%. There were no significant differences in overall survival and local tumor progression rates between medium- and large-size tumors and among BCLC stages A, B1 and B2. A complete response to ME-RFA was the only significant factor associated with improved survival (p=0.008). In conclusion, ME-RFA can effectively treat 3.1-7.0-cm sized HCCs with a comparable outcome between medium- and large-size tumors and among BCLA stages A to B2.
THE CELLULAR ORIGIN OF HUMAN IMMUNOGLOBULINS (γ2, γ1M, γ1A)
Authors: Robert C. Mellors, Leonhard Korngold
Journal: The Journal of Experimental Medicine (1963)

A study was made of the cellular origin of human immunoglobulins (gamma(2), gamma(1M), gamma(1A)). The results indicated that two closely related families of cells form immunoglobulins in human lymphoid tissue: germinal (reticular) centers and plasma cells. Thus their cellular origin in addition to their known antigenic relations further justifies placing the immunoglobulins in one family of proteins. Immunoglobulins were also formed to a small extent in primitive reticular cells which resembled those of germinal centers but were separated from them. Possibly such cells were undergoing transition to the much more numerous plasma cells with which they were commonly associated. The mantles of small lymphocytes which surrounded germinal centers did not contain detectable quantities of immunoglobulins. While in general only one type of immunoglobulin was present in an individual cell or germinal center, gamma(2)- and gamma(1M)-globulin were identified on occasion in the same plasma cell and germinal center. A peculiarity of the fetal thymus gland was the presence of immunoglobulin, mainly gamma(1M), in a small number of cells of small and intermediate size and primitive reticular appearance and in Hassall's corpuscles.
Treatment of pancreatic cancer in patients age 70 or older.
Authors: C. Christman-Skieller, G. M. Heestand, G. A. Fisher, P. L. Kunz, J. M. Ford, L. A. Columbo, D. T. Chang, A. Koong
Journal: Journal of Clinical Oncology (2010)

e14590 Background: 42,470 cases of pancreatic cancer are expected in 2009, with a median age of 72 at presentation. Appropriate therapy for elderly patients is not always clear. We report our experience using chemoradiation to treat pancreatic cancer in patients aged 70+. Methods: The radiation oncology database at the Stanford Cancer Center was queried for patients with newly diagnosed pancreatic cancer aged 70+. Pathology and treatment data was entered into a REDCap database. Patients who had undergone surgery for their tumors were classified as resectable, and patients with inoperable tumors, metastasis, or comorbidities precluding surgery were classified as unresectable. Resectable patients were treated with neoadjuvant or adjuvant radiation ± chemotherapy. Unresectable patients received conventionally fractionated or stereotactic radiation ± chemotherapy. Peri-radiation gemcitabine was defined as beginning or ending within 2 months of radiation. Survival data was determined by Kaplan-Meier analysis using SAS Enterprise Guide 4.2 software. Results: Data from 272 pancreatic cancer patients treated by the Stanford Department of Radiation Oncology has been collected to date. Of these patients, 84 patients were age 70+ at diagnosis. 20 patients underwent surgical resection, while 64 were unresectable. Survival and treatment data is summarized in the Table. Conclusions: Overall survival for patients with unresectable pancreatic cancer aged 70+ appears similar to those younger than 70, suggesting that they may also benefit from aggressive therapy. Survival data for patients aged 70+ n %n receiving gemcitabine peri-radiation Med gemcitabine cumulative dose peri-radiation (%n*, range) Med. survival Med. age (range) Resectable 20 40% 8,000 mg/m2 (35%, 1,970-11,780) 84.5 wks 75 (70-81) Unresectable 64 56% 7,370 mg/m2 (47%, 980-20,380) 46.0 wks 79 (70-92) * Patients with documented gemcitabine dosing. No significant financial relationships to disclose.
The Tea Leaves of Small Trials
Authors: David P. Harrington
Journal: Journal of Clinical Oncology (1999)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.5.1336 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10334516 The Tea Leaves of Small Trials David P. HarringtonxDavid P. HarringtonSearch for articles by this author Show More Dana-Farber Cancer Institute, Boston, MA https://doi.org/10.1200/JCO.1999.17.5.1336 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
A comparison of oncology clinicians' preferences for structuring survivorship care.
Authors: E. Gage, M. Pailler, M. Gruber, M. Kelly, J. Yasko, M. Zevon, D. Somayaji, C. Panagakis, J. Ch'ng
Journal: Journal of Clinical Oncology (2010)

e19545 Background: Several models for survivorship care are prominent within the cancer literature; however, there is little research that examines what oncology clinicians perceive to be the best approach to caring for cancer survivors and what services survivorship programs should include. Methods: A web-based survey of all clinical staff was conducted at an NCI designated comprehensive cancer center (N = 377, 57 physicians, 31 midlevel providers, 207 oncology nurses, 27 clinicians in support services, and 55 other) with a 49.8% response rate. Chi Square and one-way ANOVAs were used to examine differences between groups in their preferences for a disease site specific, single centralized multisite clinic, and community-based shared care models for the delivery of survivorship care. Results: There were significant differences in model preference by clinician type (Χ2 = 15.355, p = 0.05). Physicians and nurses preferred to base survivor programs in disease site clinics (54.3% and 46.6% respectively), followed by a centralized multisite clinic (26.1% and 27%), with the community shared model the least preferred (19.6% and 26.4%). This was also evident in the significant preference for physicians to continue management of their patients through survivorship in their home clinics (F = 2.92, p = 0.022), as well as their relative reluctance to refer to a centralized survivorship clinic (F = 17.05, p< 0.001). All four clinician groups rated providing education about late effects, pain and symptom management, and help communicating with primary care providers as among the most important components of a survivorship program. Conclusions: The findings indicate an overall preference among clinical staff for retaining survivorship programs within the primary cancer treatment setting. This preference was consistent across disciplines. Disciplines differed, however, in their preferences for retaining survivorship programs in the site-specific clinic setting, as opposed to centralizing care in a single multisite survivor clinic. Given these differences it is critical that standardized patient outcomes be included in future evaluations of survivorship programs so that the most effective care delivery models are empirically identified. No significant financial relationships to disclose.
Phase II trial of oxaliplatin (OXA) and topotecan (TOP) as a first line treatment for the patients (pts) with advanced ovarian cancer (AOC): Preliminary results of a pilot study
Authors: V. Gorbounova, S. Topchieva, N. Besova
Journal: Journal of Clinical Oncology (2005)

5116 Background: TOP with cisplatin is an active regimen though assotiated with a high degree of myelosupression in the first line therapy of ovarian cancer (ASCO 19: abstr # 1503, 2000). OXA is a 3rd generation platinum agent forming DNA adducts uniquely resistant to mismatch repair and has activity in AOC and is less myelosupressive and nephrotoxic than cisplatin. The primary aim of this phase II pilot study is to evaluate the response rate (RR) and toxicity profile. Secondary aim will be time to progression (TTP) and overall survival (OS). Methods: Patients with histologically proven AOC, compromized by cardiology and/or renal disease, FIGO stage III-IV, measurable disease, PS 0–2 and chemotherapy naive were eligible. OXA (85 mg/m2 -12 pts and 100 mg/m2 - 5 pts) was administered on day 1 (over 120 min) + TOP (1,5 mg/m2- 17pts) on days 2–4 (over 30 min) every 21 days. Results: 17 pts were enrolled in study. Median age was 49,9 years (range 34–65); FIGO III-IV (10 and 7 pts); PS 0–1-2 (1–11-5 pts); histology: serous -14 and endometrioid adenocarcinoma - 3 pts; 5 (29,4%) pts had been previously treated with only one platinum-based regimen (median - 4,4 courses) with more than 12 months treatment - free interval and 12 (70,5%) were untreated. Results: all 17 pts were suitable for evaluation. 5 pts had CR (29,4%), 7 PR (41,1%), 4 SD (23,5%) and 1 PD (5,8%). 12 pts (RR -70,5%) responded to OXA + TOP regimen. The total number of cycles administered was 79, median - 5 (range 2–8) cycles per pts. Grade (gr) III-IV hematological toxicity in 75 evaluable cycles were: neutropenia gr III - 13 (17,3%), gr IV - 5 (6,6%) include 1 febrile case; anaemia and thrombocytopenia gr III - 2 (2,6%) and 7 (9,3%), gr IV - none. Gastrointestinal toxicity was moderate: nausea gr I-II was in 53 (70,6%) cycles, vomiting gr I-II - 16 (21,4%), diarrhea gr I-II - 7 (9,3%), constipation gr I-II - 7 (9,3%). No cases of nephrotoxicity. Gr I/II peripheral neuropathy was noted in 2 (11,7%)/2 (11,7%) pts. Conclusions: The combination of OXA with TOP represents an active and tolerable regimen for AOC. Toxicity profile was acceptable. The trial continues and results will be presented. No significant financial relationships to disclose.
Microfluidics for High-Throughput Quantitative Studies of Early Development
Authors: Thomas J. Levario, Bomyi Lim, Stanislav Y. Shvartsman, Hang Lu
Journal: Annual Review of Biomedical Engineering (2016)

Developmental biology has traditionally relied on qualitative analyses; recently, however, as in other fields of biology, researchers have become increasingly interested in acquiring quantitative knowledge about embryogenesis. Advances in fluorescence microscopy are enabling high-content imaging in live specimens. At the same time, microfluidics and automation technologies are increasing experimental throughput for studies of multicellular models of development. Furthermore, computer vision methods for processing and analyzing bioimage data are now leading the way toward quantitative biology. Here, we review advances in the areas of fluorescence microscopy, microfluidics, and data analysis that are instrumental to performing high-content, high-throughput studies in biology and specifically in development. We discuss a case study of how these techniques have allowed quantitative analysis and modeling of pattern formation in the Drosophila embryo.
Abstract 9448: The Association Between Adiponectin and Type 2 Diabetes and Hypertension in African American Men and Women: The Jackson Heart Study
Authors: Sharon K Davis, Samson Gebreab, Ruihua Xu, Pia Riestra, Rumana Khan, Anne Sumner, DeMarc Hickson, Aurelian Bidulescu
Journal: Circulation (2014)

Introduction:  The objective of this study was to assess the effect of adiponectin and its interaction with socioeconomic status (SES) on likelihood of type 2 diabetes and hypertension in 3,663 African American men and women in the Jackson Heart Study.   Hypothesis:  It was hypothesized that, after adjusting for confounders, men and women with lower levels of adiponectin would have significantly higher risk of type 2 diabetes and hypertension.   Methods:  Separate logistic regression models for type 2 diabetes and hypertension were stratified by sex. Models were analyzed with adiponectin as the primary predictor divided into 4 quartiles with quartile 4 as the highest level and the reference. Sequential multivariate models included age, biological indices (low-density lipoprotein, high-density lipoprotein, total cholesterol, homoeostasis model assessment [[Unable to Display Character: –]] insulin resistance, C-reactive protein), behavioral indices (body mass index, smoking status, physical activity, alcohol consumption status), a fully adjusted model including SES based on annual household income collapsed into 3 categories  p     Results:  There was no association between adiponectin and type 2 diabetes and hypertension among men. There was an interaction among men who had the lowest level of adiponectin and SES and the likelihood of type 2 diabetes (odds ratio [OR], 95% confidence interval [CI] = 4.77, [0.79, 6.68],  p  = .02). Adiponectin level was inversely associated with type 2 diabetes among women (OR, 95% CI = 1.47, [1.02, 2.11],  p  = .04). Women with the lowest level of adiponectin were less likely to be hypertensive (OR, 95% CI = 0.66 [0.46, 0.95],  p  = .02). There was an interaction among women with the lowest levels of adiponectin and SES being less likely to be hypertensive (OR, 95% = 0.43, [0.25, 0.76], 0.48, [0.36, 0.93],  p  = .03 and .03, respectively).   Conclusion:  Findings reveal significant differential associations between adiponectin and type 2 diabetes and hypertension, including an interaction with SES among AA men and women.
Bisphosphonate-induced osteonecrosis of the jaw: Incidence and risk factors in patients with breast cancer and gynecological malignancies
Authors: V. Beck, E. Solomayer, M. Krimmel, C. Reinert, T. Fehm
Journal: Journal of Clinical Oncology (2007)

1113 Background: Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. They are successfully used in conditions of increased bone turnover such as osteoporosis or bone metastases. Since 2003 multiple cases of bisphosphonate-induced osteonecrosis of the jaw (ONJ) were reported. Our purpose was to describe the incidence and risk factors of ONJ in patients with breast cancer or gynecological malignancies. Patients and Methods: ONJ was assessed retrospectively for all patients with breast cancer or gynecological malignancies treated with bisphosphonates at the Department of Gynecology and Obstetrics, University Hospital Tuebingen during April 1999 until May 2006. Results: 10 of 310 (3%) patients with breast cancer or gynecological malignancies developed ONJ while receiving bisphosphonate therapy. All patients with ONJ were treated for bone metastases. Except one all patients with ONJ had a history of recent dental procedures. All patients had received zoledronic acid as part of their bisphosphonate regimen. In 4 of 10 patients this was the only bisphosphonate given. The remaining 6 patients had received at least one of the other bisphosphonates (alendronate, ibandronate, clodronate or pamidronate) before or after zoledronic acid therapy during their course of disease. Time of exposure to bisphosphonates and the number of treatment cycles were significant risk factors for the development of ONJ (p&lt;0.001). In patients diagnosed with ONJ the mean number of treatment cycles was 27 ±18 cycles (median: 21 cycles, range 6–62 cycles) and the mean duration of bisphosphonate therapy was 29 ±20 months (median: 22 months, range 1–67 months). In contrast, the mean number of treatment cycles in patients without manifestation of ONJ was 11 ±12 cycles (median: 6 cycles, range 1–90 cycles). The mean duration of therapy was 12 months (median: 7 months, range 1–81 months). Conclusion: Osteonecrosis of the jaw is regarded a major side effect of bisphosphonate therapy. Length of exposure to bisphosphonates and the number of treatment cycles seem to be the most important risk factors for the development of ONJ. In addition, recent dental procedures favours the development of an ONJ. No significant financial relationships to disclose.
Bronchoscopic lung volume reduction - a descriptive case series: The Cambridge experience
Authors: Jurgen Herre, Tom Dymond, Pasupathy Sivasothy, Ravi Mahadeva
Journal: European Respiratory Journal (2013)

Introduction  Bronchoscopic Lung Volume Reduction (BLVR) is an evolving alternative to medical therapy for severe emphysema. We have developed a service using endobronchial valves(Pulmonx) including COPD physician, radiologist, interventional bronchoscopist and thoracic surgeon.  Aims and objectives  We report our experience of BLVR over 4 years in a case-based fashion, and describe the diversity of benefits achieved.  Methods  Retrospective analysis of 6 cases from 2009–2012 selected by CT (fissure integrity) or Chartis (collateral ventilation). We show pooled data for lung function changes over 6 and 6-18 months post-procedure as well as describe individual case benefit by objective and subjective measures.  Results  From baseline, 6 month FEV1 improved by 30.1% (selection by CT 26.7% and Chartis 33.6%) and residual volume (RV) fell by 16.6%. This was maintained over 7-18 months for both FEV1 (+29.6%) and RV (-13.7%). Individuals demonstrated numerous measurable and perceived benefits not captured by FEV1, including improved 6 minute walk, decreased exacerbation frequency and breathlessness, improved stair climbing, decreased exertional rest and oxygen requirements.  Conclusions  1.Patient selection is critical to outcome. Our model includes, careful specialist COPD phenotyping, dedicated lung Physiology and Radiology, skilled interventional Bronchoscopy and comprehensive Audit of outcomes. 2.FEV1 is a limited tool when used in isolation. 3.Time to benefit is variable, some patients taking many months to achieve substantial benefits. 4.Index of benefit can be primarily subjective and we propose a multi-dimensional procedure-specific outcome score to capture both objective and subjective improvements.