tbuckley/cabot-search huggingface dataset:
The association between RT-induced changes in lung density and global lung function
Authors: J. Ma, J. Zhang, S. Zhou, J. L. Hubbs, R. J. Foltz, D. R. Hollis, K. L. Light, T. Z. Wong, C. R. Kelsey, L. B. Marks
Journal: Journal of Clinical Oncology (2008)

13543 Background: Radiation (RT)-induced lung injury is a common side effect following thoracic RT. The study of RT-induced lung injury is complicated by the multiple endpoints considered (e.g., radiologic vs. symptomatic vs. functional). The association between these endpoints is not entirely clear. We herein assess the association between RT-induced changes in computed tomography (CT)-defined lung density and pulmonary function tests (PFTs). Methods: As part of a prospective clinical study, patients receiving incidental partial lung irradiation underwent PFTs and CT scans before and serially 3–6 months after RT. Patient characteristics are as follows: the majority of patients presented with lung cancer (82%), median age was 62 (range 22–87), 50% received chemotherapy, the median prescribed RT dose was 64 Gy (range 23–86 Gy), and the median mean lung dose (MLD) was 17 Gy (4–36 Gy). Regional lung density was assessed by CT scans and global lung function by PFTs. The percent reductions in PFTs were compared to the average changes in lung density using Pearson correlations. Results: 111 patients had a total of 203 concurrent CT lung density and PFT evaluations during 3- to 24-month post-RT follow-up intervals available for analyses. The average changes in lung density were quantitatively related to the percent reductions in PFTs, albeit with modest correlation coefficients (r), (see table). The results were similar in patients treated with and without chemotherapy. Conclusions: There is a quantitative association between the degree of increase in lung density as defined by CT and the percent reduction in PFTs. These results support the concept of a parallel architecture within the lung where the sum of regional injury may be associated with changes in global function. Pearson correlation between the average increases in lung density and reductions in PFTs r p- value All patients CT vs. DLCO 0.26 <0.001 CT vs. FEV1 0.34 <0.001 Patients treated with chemotherapy CT vs. DLCO 0.34 <0.001 CT vs. FEV1 0.39 <0.001 Patients treated without chemotherapy CT vs. DLCO 0.17 0.085 CT vs. FEV1 0.29 0.004 Abbreviations: DLCO = diffusion copacity for carbon monoxide; FEV1 = forced expiratory volume in 1s Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Varian Medical Systems
Opioid Requirements to Control Mucositis During Chemoradiotherapy in Head and Neck Cancer: Cisplatin Vs. Cetuximab
Authors: Lina Inagaki, Kenji Nakano, Yasuyoshi Sato, Junichi Tomomatsu, Yukiko Sato, Takashi Toshiyasu, Kazuyoshi Kawabata, Shunji Takahashi
Journal: Annals of Oncology (2014)
Significance of serum colony-stimulating factor-1 as a breast cancer marker
Authors: S. Aharinejad, A. Thomas, C. Singer, E. Kubista, P. Paulus, A. Miksovsky, D. Abraham
Journal: Journal of Clinical Oncology (2009)

11071 Background: A specific and sensitive biomarker that indicates the presence of breast cancer is highly desirable, yet available markers are of limited value. Colony-stimulating factor-1 (CSF-1) is involved in mammary gland development and mediates breast cancer progression. Earlier work indicated correlation of serum CSF-1 with breast cancer staging, and a recent report suggests that CSF-1 is a potential breast cancer marker, however the data reported so far await validation. Methods: In a prospective study in 799 women with no history of malignant disease undergoing surgery, serum CSF-1 levels were measured by a commercially available ELISA. In this cohort, 312 patients had breast cancer and 487 age-matched women had benign tumors. The tumor size, nodal and metastasis status, histological tumor type, hormone and human epidermal growth factor receptor 2 (HER2) and menopausal status were evaluated. Mean CSF-1 serum concentrations were compared between the patient groups by non-parametric Wilcoxon two-sample and Kruskal-Wallis test. The area under the receiver operating characteristic curve was calculated by logistic regression. Results: Mean serum CSF-1 concentrations were significantly higher in all patients with malignant tumors (502±429 pg/mL) as compared to those with benign tumors (382±344 pg/mL) (p&lt;0.0001, Wilcoxon). Increased CSF-1 concentrations were significantly related to malignant versus non-malignant disease in logistic regression and receiver operating characteristic analysis (p&lt;0.0001, AUC=0.6). Increased CSF-1 levels in patients with malignant tumors were associated with postmenopausal (p=0.0038) but not premenopausal (p=0.94) status (Wilcoxon). Serum CSF-1 concentrations did not correlate significantly with tumor size, nodal and metastasis status, hormone receptor and HER2 status of patients (Kruskal-Wallis). Conclusions: Our data suggest that serum CSF-1 could serve as a breast cancer marker in postmenopausal women. While its serum levels are not related to breast cancer stage at diagnosis, they might be useful for breast cancer screening in postmenopausal women. No significant financial relationships to disclose.
Phase II pilot study of neoadjuvant cetuximab in combination with cisplatin and gemcitabine in patients with resectable IB-IIIA non small cell lung cancer
Authors: L. E. Coate, K. Gately, M. P. Barr, J. Meaney, F. O’Connell, S. Nicholson, E. McGovern, V. Young, K. O’Byrne
Journal: Journal of Clinical Oncology (2006)

17107 Background: Adjuvant and neoadjuvant chemotherapy play a role in optimising long term outcome of patients with resectable non small cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase which is overexpressed NSCLC. Cetuximab is a monoclonal antibody which attaches to the extracellular domain of the EGFR preventing ligand binding. Preclinical data and phase II evidence in advanced NSCLC suggest cetuximab potentiates the effect of conventional cytotoxic agents. Methods: Patients with histologically confirmed resectable stage IB-IIIA NSCLC and adequate end-organ function, giving informed written consent are eligible. Three weekly cycles of cisplatin 80 mg/m 2 D1, gemcitabine 1250 mg/m 2 D1,D8 and cetuximab loading dose of 400 mg/m 2 on first infusion, thereafter weekly 250 mg/m 2 are used. The primary endpoint is response rate (radiological and pathological). Secondary endpoints are safety and tolerability of the combination, resection rate following therapy, overall survival and relapse free survival. In addition, molecular prognostic and predictive biomarkers of response are being assessed. Sequential samples of tissue, plasma, serum and white blood cells are being collected before, during and after therapy on all patients. Results: 16 patients have been recruited to date. (10 men, 6 women). Median age 66 (range 29–76). 3 patients stage I, 4 patients, stage II, 9 patients stage III. 11 have completed treatment. Response (RECIST guidelines); PR - 6 patients, SD - 4 patients, PD - 1 patient. The most common toxicity was skin rash (100%). Grade 3/4 toxicities were neutropenia (73%), thrombocytopenia (45%). There were 2 grade 3 and 2 grade 4 cardiovascular toxicities in patients with significant co-morbid cardiovascular histories. Conclusion: The response rate is consistent with that established for neoadjuvant chemotherapy. Ongoing biomarker studies may identify those patients most likely to benefit from induction treatment. No significant financial relationships to disclose.
Virus-Associated Cancers in Greenland: Frequent Hepatitis B Virus Infection But Low Primary Hepatocellular Carcinoma Incidence&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Mads Melbye, Peter Skinhèj, Nils Høgaard Nielsen, Bent Faber Vestergaard, Peter Ebbesen, Jens P. Hart Hansen, Robert J. Biggar
Journal: JNCI Journal of the National Cancer Institute (1984)

The incidence of primary hepatocellular carcinoma (PHC) in Greenland between 1960 and 1981 was determined and compared with the rate of this disease in Denmark. The annual age and sex rate (per 100,000) was not significantly different (overall, 1.9 vs. 2.2) despite a large difference in the prevalence of hepatitis B surface antigen (HBsAg) and anti-HBs markers of hepatitis. On the basis of a recent report of a very strong risk of PHC among male HBsAg carriers, 4.0 cases of PHC per year were expected in male Eskimos, but only 0.2 cases per year were observed. The incidence rates of other cancers suggested to be virally associated, including nasopharyngeal carcinoma, salivary gland cancer, and carcinoma of the cervix, were all high in Greenland compared to rates for the Danish population, and these high incidence rates are in accord with the markedly higher prevalences in Greenland Eskimos of viruses with which these other cancers have been associated. Thus Greenland Eskimos do not have a high incidence of PHC despite a high prevalence of HBsAg carriers, which suggests that other carcinogenic factors in this environment may be absent or that protective factors are present.
Disease activity in psoriatic arthritis (PsA): defining remission and treatment success using the DAPSA score
Authors: Monika M Schoels, Daniel Aletaha, Farideh Alasti, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2015)

The Disease Activity Index for Psoriatic Arthritis (DAPSA) is a valid and discriminative tool. Definitions of disease activity states and therapeutic response are still missing. We derived such criteria for the DAPSA.We retrieved 30 patient profiles from an observational database including joint counts, patient pain and global activity ratings and C-reactive protein (CRP) and carried out a survey among experts to classify patients into remission (REM), low (LDA), moderate (MDA) or high (HDA) disease activity. Based on the distributions of DAPSA in each of these expert-assigned states we defined the cutpoints between groups. We performed similar analyses evaluating a clinical score (cDAPSA), omitting CRP. To define minor, moderate and major treatment response, we used Cohen's Kappa statistics and analysed agreement of DAPSA percentage change with ACR20/50/70-response in three randomised controlled trials.Our survey yielded a response rate of 75% (n=33). Mean DAPSA differed significantly between patients classified as REM, LDA, MDA or HDA (p<0.001). Based on the distributions of DAPSA in these groups, we propose cut-off values of ≤4 for REM, >4 and ≤14 for LDA, >14 and ≤28 for MDA and >28 for HDA. We observed best agreement with ACR20/50/70-response at DAPSA changes of 50/75/85%, reflecting minor, moderate and major improvement.The DAPSA constitutes a disease-specific, validated and feasible tool for PsA assessment. In this study, we provide criteria for disease activity states and treatment response. They are based on an international expert survey, and show good performance in clinical trials and observational data.
Gemcitabine (Gem), cisplatin (Cis) and radiation therapy (RT) for patients with locally advanced pancreatic adenocarcinoma (ACA): A North Central Cancer Treatment Group (NCCTG) phase II study
Authors: M. G. Haddock, R. Swaminathan, S. R. Alberts, M. D. Hauge, N. R. Foster, J. A. Martenson, R. M. Goldberg
Journal: Journal of Clinical Oncology (2004)

4121 Background: In vitro studies suggest that low dose GEM sensitizes cells to RT for 48 hours following exposure. CIS is a radiation sensitizer and may result in synergistic cytotoxicity when combined with GEM. This phase II study was conducted to determine the efficacy of RT with concomitant GEM and CIS in patients (pts) with locally advanced pancreatic ACA. Methods: GEM and CIS were delivered twice weekly during the first 3 weeks of RT using the phase I study MTD of GEM 30 mg/m2 and CIS 10 mg/m2. RT dose was 45 Gy (180 cGy/fx) to the primary tumor and regional nodes with a 5.4 Gy boost to the gross tumor volume. Four weeks post-RT, pts received GEM 1000 mg/m2 3 weeks out of 4 for 12 weeks. Survival at 12 months (mos) was the primary endpoint with secondary endpoints of time to progression (TTP), toxicity and quality of life(QOL). Planned accrual was 45 pts with a requirement that 13 of 20 or 23 of 45 survive 12 mos as evidence of promising activity. Results: 48 pts were enrolled in 22 mos; 20 were evaluable for survival endpoints. Survival at one year was 30% (6/20, 95% CI: 15–53%), median survival was 8.8 mos (95% CI: 5.9–13) and median TTP was 7.1 mos (95% CI: 2.6–8.2). Overall QOL scores (SDS, LASA) did not significantly change over time, but 5 individual QOL subscales significantly improved (insomnia, outlook, depression (SDS); frequency of pain (SDS, LASA)). 47 pts were evaluable for adverse events (AEs). 42 (89%) and 12 pts (26%) experienced at least one grade 3+ or grade 4+ AE, respectively, with one grade 5 AE (melena). Frequently occurring grade 3+ AEs are shown below: Conclusions: Survival results in the initial 20 pts treated with GEM, CIS, and RT for locally advanced pancreatic ACA did not meet our predefined criteria for success. Future studies will focus on novel agents in addition to RT in this setting. Supported by Grant CA-25224. No significant financial relationships to disclose.
HIV Testing and Service Delivery Among Black Females — 61 Health Department Jurisdictions, United States, 2012–2014
Authors: Renee Stein, Taran Pierce, Natasha Hollis, Jennifer Smith
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

A primary goal of the national human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) Strategy is to reduce HIV-related health disparities (1). Among all HIV diagnoses among women in the United States in 2014, non-Hispanic black or African American (black) women accounted for an estimated 62% of diagnoses, despite constituting only 13% of the female population (2,3). Although HIV diagnoses continue to occur disproportionately among black women, HIV surveillance data indicate a 13.5% decrease in diagnoses from 2012 to 2014 (2,4). However, widespread HIV testing and early linkage to care are critical for persons with HIV to achieve viral suppression and improved health outcomes, and to reduce transmission of HIV to others (5). Analysis of CDC-funded program data on HIV testing services provided to black females and submitted by 61 state and local health departments during 2012-2014 revealed that the number of new HIV diagnoses among black females decreased 17% from 2,177 in 2012 to 1,806 in 2014. Among black females with newly diagnosed HIV infection, the percentage who were linked to HIV medical care within 90 days of diagnosis increased 48.2%, from 33.8% in 2012 to 50.1% in 2014. However, in 2010 the National HIV/AIDS Strategy established a goal to link 85% of persons with newly diagnosed HIV infection to HIV medical care (1). Enhanced efforts to diagnose HIV infection among black females and link them to HIV medical care are critical to address HIV infections in the United States.
Can individuals with colonic polyposis be managed safely with colonoscopic surveillance?
Authors: Andrew Kaz, Jason Dominitz
Journal: Endoscopy (2015)

The eventual consequence faced by many individuals with one of the heritable colon polyposis syndromes is an elective colectomy. According to recent guidelines that address the management of familial adenomatous polyposis (FAP), attenuated FAP, or MUTYH-associated polyposis, the absolute indications for immediate colectomy include documented or suspected cancer or significant symptoms, and relative indications for colectomy include the presence of multiple adenomas > 6 mm, a significant increase in adenoma number, and inability to adequately survey the colon endoscopically because of multiple diminutive polyps [1]. With respect to FAP, these guidelines reflect the premise that colorectal cancer (CRC) is the inevitable outcome unless the colon is removed [2] [3]. Much of what we know about the natural history of FAP is derived from the St. Mark’s FAP registry in London, where the average age at cancer diagnosis was 39 years, with cancer developing in 93 % of patients by the age of 50 years [4].
Abstract 19548: Detection, Correlation and Prediction of Systemic Vascular Disease using 3D volumetric Carotid Ultrasound: Results from the High Risk Plaque Initiative
Authors: Usman Baber, Samantha Sartori, Roxana Mehran, Pieter Muntendam, Mario J Garcia, Henrik Sillesen, Erling Falk, Valentin Fuster
Journal: Circulation (2012)

Purpose We sought to determine the prevalence and clinical correlates of carotid atherosclerosis using novel 3D ultrasound imaging. Methods In the High-Risk Plaque (HRP) Initiative, 3690 asymptomatic, at-risk adults underwent non-invasive imaging for evaluation of subclinical atherosclerosis in the carotid arteries using duplex ultrasound for measurement of plaque volume (3D) and intima-media thickness (IMT). Coronary artery calcification (CAC) was assessed using computed tomography (CT). Plaque volume in the right and left carotid arteries was averaged and patients were categorized by tertiles of increasing plaque volume. The prevalence and clinical correlates of carotid atherosclerosis were compared across groups. Discrimination for CAC detection using 3D carotid ultrasound versus IMT was also assessed with receiver operating curve (ROC) analysis. Results Any carotid atherosclerosis was common, detectable in 70% of participants using 3D carotid ultrasound. Greater carotid atherosclerotic burden was associated with increasing age, lower high-density lipoprotein cholesterol, smoking, white race and male gender (p&lt;0.05 for all comparisons). Carotid atherosclerosis was also strongly associated with CAC as the prevalence of CAC &gt; 100 was 20.3%, 34.6%, 50.1% and 62.2% across groups (p&lt;0.001). Discrimination for detection of CAC was also higher using 3D carotid ultrasound compared to IMT with c-statistics of 0.69 and 0.59 for CAC &gt; 100; and 0.71 and 0.59 for CAC &gt; 400, respectively (Figure). Conclusion In this large observational study, carotid atherosclerosis as detected by 3D volumetric ultrasound is highly prevalent and associated with traditional risk factors. Compared to IMT, carotid atherosclerosis as visualized by 3D ultrasound is a better predictor of CAC, suggesting that this novel modality may be superior to IMT in detection of systemic vascular disease.
Phosphodiesterase inhibitors as promising therapies for cigarette smoke-induced emphysema and pulmonary hypertension (PH) in mice
Authors: Michael Seimetz, Nirmal Parajuli, Alexandra Pichl, Ralph Theo Schermuly, Friedrich Grimminger, Werner Seeger, Hossein Ardeschir Ghofrani, Norbert Weissmann
Journal: European Respiratory Journal (2014)

Introduction:  The pulmonary vascular tone is, amongst others, controlled by the second messengers cyclic GMP and AMP. In vascular diseases such as chronic obstructive pulmonary disease (COPD) and PH, these mediators seem to be less available, either by decreased activity of the respective G-proteins, such as soluble guanylate cyclase (sGC) (producing) or increased phosphodiesterase (PDE) activity (degrading).   Aims : Own observations showed that the stimulation of sGC prevented emphysema and PH. Based on this we here ask if a downstream inhibition of PDEs could also have preventive effects.   Methods:  C57BL6/J mice were exposed to cigarette smoke for 6 hours/day, 5 days/week for 6 months (particulate matter 140 mg/m 3 ). In parallel with smoke exposure mice were treated either with Placebo, the PDE 5 inhibitor Tadalafil, the PDE4 inhibitor Piclamilast or both once daily by gavage. Alveolar (compliance, alveolar morphometry) and vascular (right ventricular systolic pressure [RVSP], vascular morphometry) alterations as well as changes in right ventricular heart weight were determined after 6 months.   Results:  Smoke exposure caused development of emphysema (reflected by worsened lung function and increased mean linear intercept and airspace) and PH (shown by increased RVSP, vessel muscularization, and right heart hypertrophy [RHHT]) in placebo-treated mice, but not in PDE inhibitor-treated mice.   Conclusions:  The inhibition of PDE4 or 5 prevented the development of cigarette smoke-induced emphysema, PH and RHHT showing that these enzymes could potentially be targets for therapeutic approaches.  Funded by: DFG, Excellence Cluster Cardio-Pulmonary System (ECCPS).
Tumor Necrosis Factor Receptor-Associated Factor 1 Is Overexpressed in Reed-Sternberg Cells of Hodgkin’s Disease and Epstein-Barr Virus-Transformed Lymphoid Cells
Authors: Horst Dürkop, Hans-Dieter Foss, Gudrun Demel, Heike Klotzbach, Corinna Hahn, Harald Stein
Journal: Blood (1999)
Anastomotic Blood Flow in Experimental Myocardial Infarction: A new method, using 133Xenon clearance, for repeated measurements during recovery
Authors: J. R. Rees, V. J. Redding
Journal: Cardiovascular Research (1967)

After tying the anterior descending coronary artery in dogs, solutions of 133Xenon were injected into the vessels of the infarct through a fine catheter over 10 days. The clearance of isotope, determined by an external counter, was a measure of anastomotic blood flow. Initially, mean flow was reduced to 25% of normal. After the third day, clearance rates increased, together with enlargement of interarteriolar anastomoses within the heart.
Is the adjustment of serum creatinine level &lt; 0.6 mg/dl to 0.6 mg/dl justified in estimates of carboplatin clearance calculated by the Jelliffe formula?
Authors: S. Nagao, K. Fujiwara, R. Kagawa, Y. Kozuka, T. Oda, K. Maehata, H. Ishikawa, H. Koike, E. Aotani, I. Kohno
Journal: Journal of Clinical Oncology (2006)

5072 Background: The Jelliffe formula (JF) does not include body surface area (BSA) or body weight to adjust the body size. We demonstrated that estimates of carboplatin clearance calculated by the JF tend to have greater positive bias compared to other formulae. The JF has been used to estimate carboplatin clearance in Gynecologin Oncology Group studies. In patients with serum creatinine level &lt;0.6 mg/dl, it is adjusted to 0.6 mg/dl in estimates of carboplatin clearance (Adjusted-Jelliffe formula (AJF)). The purpose of this study is to evaluate whether this adjustment is suitable. Methods: Carboplatin clearance was estimated in 115 patients with serum creatinine &lt;0.6 mg/dl who received carboplatin-based chemotherapy for gynecologic malignancies between January 1996 and August 2004. Creatinine clearance was estimated using the Cockroft-Gault formula (CGF), JF, and AJF. The median percent error (MPE) and the median absolute percent error (MAPE) were evaluated by comparing carboplatin clearance. The relationships between BSA and ratios of estimated carboplatin clearance (JF/CGF, AJF/CGF) were evaluated by using simple regression. Results: The estimated carboplatin clearances were: CGF, 126.7 ± 27.7; JF, 148.2 ± 20.5; AJF, 130.5 ± 14.3. Comparing the results of the CGF with the JF, AJF yielded MPEs of +20%, +6%, and MAPEs of 21%, 14%, respectively. There were the linear correlations between ratio of estimated carboplatin clearances and BSA (Y 1 = −1.141X + 2.830, Y 2 = -1.061 X + 2.581, Y 1 : ratio of carboplatin clearance (JF/CGF), Y 2 : ratio of carboplatin clearance (AJF/CGF), X: BSA). Conclusions: As expected, carboplatin clearance was decreased by adjusting serum creatinine to 0.6 mg/ml, but it did not adjust the bias by BSA. Estimates of carboplatin clearance calculated by the AJF tend to have greater negative bias, particularly when the BSA of the patient is large. No significant financial relationships to disclose.