tbuckley/cabot-search huggingface dataset:
Optimization of Epoetin Therapy with Intravenous Iron Therapy in Hemodialysis Patients
Authors: ANATOLE BESARAB, NEETA AMIN, MUHAMMAD AHSAN, SUSAN E. VOGEL, GARY ZAZUWA, STANLEY FRINAK, JAMES J. ZAZRA, J. V. ANANDAN, AJAY GUPTA
Journal: Journal of the American Society of Nephrology (2000)

Iron deficiency limits the efficacy of recombinant human erythropoietin (rhEPO) therapy in end-stage renal disease (ESRD) patients. Functional iron deficiency occurs with serum ferritin >500 ng/ml and/or transferrin saturation (TSAT) of 20 to 30%. This study examines the effects of a maintenance intravenous iron dextran (ivID) protocol that increased TSAT in ESRD hemodialysis patients from conventional levels of 20 to 30% (control group) to those of 30 to 50% (study group) for a period of 6 mo. Forty-two patients receiving chronic hemodialysis completed a 16- to 20-wk run-in period, during which maintenance ivID and rhEPO were administered in amounts to achieve average TSAT of 20 to 30% and baseline levels of hemoglobin of 9.5 to 12.0 g/dl. After the run-in period, 19 patients randomized to the control group received ivID doses of 25 to 150 mg/wk for 6 mo. Twenty-three patients randomized to the study group received four to six loading doses of ivID, 100 mg each, over a 2-wk period to achieve a TSAT >30% followed by 25 to 150 mg weekly to maintain TSAT between 30 and 50% for 6 mo. Both regimens were effective in maintaining targeted hemoglobin levels. Fifteen patients in the control group and 17 patients in the study group finished the study in which the primary outcome parameter by intention to treat analysis was the rhEPO dose needed to maintain prestudy hemoglobin levels. Maintenance ivID requirements in the study group increased from 176 to 501 mg/mo and were associated with a progressive increase in serum ferritin to 658 ng/ml. Epoetin dose requirements for the study group decreased by the third month and remained 40% lower than for the control group, resulting in an overall cost savings in managing the anemia. Secondary indicators of iron-deficient erythropoiesis were also assessed. Zinc protoporphyrin did not change in either group. Reticulocyte hemoglobin content increased only in the study group from 28.5 to 30.1 pg. It is concluded that maintenance of TSAT between 30 and 50% reduces rhEPO requirements significantly over a 6-mo period.
Features of occupational asthma in Northern Italy from 1987 to 2012
Authors: Gabriella Guarnieri, Ilaria Cattoni, Grazia Barbetta, Filippo Liviero, Paola Mason, Maria Cristina Scarpa, Piero Maestrelli
Journal: European Respiratory Journal (2013)

Occupational asthma (OA) is a frequent work-related respiratory disease, accounting for 15% of all causes of asthma. In recent years there has been an improvement in working conditions and a redistribution of the work force, that may have modified the features of OA.

The aim of study was to describe retrospectively the distribution and characteristics of OA diagnosed in a third level center during the last decays.

All cases of OA diagnosed in the Occupational Medicine Unit of University of Padova from 1987 to 2012 were analysed, including causes and jobs, contribution of migrant workers and clinical features.

We detected 424 cases of OA: 299 were males and 125 females, with mean age at diagnosis 37±11 ys. The most frequent causes were isocyanates (61%), flours (10%), latex (4.7%), wood (4%), pet epithelia (3.6%), persulphates (3%). The most frequent jobs in both sexes were painters (58%), food industry workers (11%) and carpenters (10%), while there was a greater contribution of women for the health care employees (5%) and hairdressers (3%). Total number of OA diagnosed per year decreased from early nineties to 2012 (from 30 to 5 cases). OA in migrants was observed in 7.5% of total cases and the proportion increased from 0.7% in 1987-1991 period to 36.4% in the last five years. Along the study period we showed an homogenous distribution of OA in reference to gender, age at diagnosis, causes and jobs. OA in in painters was significantly more frequent in migrants than in non migrants (46.9% vs 18.6%, p<0.001).

In conclusion, the overall number of new cases of OA decreased in the last decay, while the proportion of OA diagnosed in migrant workers increased.
Biomarkers Associated with Clinical Activity of Pd-L1 Blockade in Non-Small Cell Lung Cancer (Nsclc) Patients (Pts) in a Phase I Study of Mpdl3280A
Authors: J-C. Soria, S. Gettinger, M. Gordon, R.S. Heist, L. Horn, D.R. Spigel, M. Kowanetz, A. Mokatrin, Y. Xiao, A. Sandler, E. Felip
Journal: Annals of Oncology (2014)
Sequential Dose-Dense Doxorubicin, Paclitaxel, and Cyclophosphamide for Resectable High-Risk Breast Cancer: Feasibility and Efficacy
Authors: C. Hudis, A. Seidman, J. Baselga, G. Raptis, D. Lebwohl, T. Gilewski, M. Moynahan, N. Sklarin, D. Fennelly, J. P.A. Crown, A. Surbone, M. Uhlenhopp, E. Riedel, T. J. Yao, L. Norton
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Dose-dense chemotherapy is predicted to be a superior treatment plan. Therefore, we studied dose-dense doxorubicin, paclitaxel, and cyclophosphamide (A → T → C) as adjuvant therapy. METHODS: Patients with resected breast cancer involving four or more ipsilateral axillary lymph nodes were treated with nine cycles of chemotherapy, using 14-day intertreatment intervals. Doses were as follows: doxorubicin 90 mg/m 2 × 3, then paclitaxel 250 mg/m 2 /24 hours × 3, and then cyclophosphamide 3.0 g/m 2 × 3; all doses were given with subcutaneous injections of 5 μg/kg granulocyte colony-stimulating factor on days 3 through 10. Amenorrheic patients with hormone receptor-positive tumors received tamoxifen 20 mg/day for 5 years. Patients treated with breast conservation, those with 10 or more positive nodes, and those with tumors larger than 5 cm received radiotherapy. RESULTS: Between March 1993 and June 1994, we enrolled 42 patients. The median age was 46 years (range, 29 to 63 years), the median number of positive lymph nodes was eight (range, four to 25), and the median tumor size was 3.0 cm (range, 0 to 11.0 cm). The median intertreatment interval was 14 days (range, 13 to 36 days), and the median delivered dose-intensity exceeded 92% of the planned dose-intensity for all three drugs. Hospital admission was required for 29 patients (69%), and 28 patients (67%) required blood product transfusion. No treatment-related deaths or cardiac toxicities occurred. Doxorubicin was dose-reduced in four patients (10%) and paclitaxel was reduced in eight (20%). At a median follow-up from surgery of 48 months (range, 3 to 57 months), nine patients (19%) had relapsed, the actuarial disease-free survival rate was 78% (95% confidence interval, 66% to 92%), and four patients (10%) had died of metastatic disease. CONCLUSION: Dose-dense sequential adjuvant chemotherapy with doxorubicin, paclitaxel, and cyclophosphamide (A → T → C) is feasible and promising. Several ongoing phase III trials are evaluating this approach.
A Cholesterol Derivative (24-Ethyl-Cholestane- 3Β,5&amp;Agr;,6&amp;Agr;-Triol ) with Antitumor Activity in Advanced Refractory or Recurrent Hodgkin Lymphomas
Authors: N.F. Habib, H.E. Daaboul, G. Hage, A. Jabbour, H. Zeitouni, N. Kassem, A. Yammine
Journal: Annals of Oncology (2014)
Determinants of respiratory disturbance and oxygen saturation drop indices in obstructive sleep apnoea syndrome
Authors: MA Quera-Salva, C Guilleminault, M Partinen, A Jamieson
Journal: European Respiratory Journal (1988)

Although chronic sleep fragmentation and oxygen saturation (Sao2) drops alone do not induce obstructive sleep apnoea (OSA), both are part of the feedback loop leading to obstructive sleep apnoea syndrome (OSAS). To determine factors in respiratory disturbance and Sao2 drops, we used polysomnographic and cephalometric data from 120 OSAS patients to construct a model which we then applied prospectively to 25 new OSAS patients, calculating the correlation between observed and predicted values. We found body mass index and the amount of stage 1 non-rapid eye movement sleep to be significant variables when considering both the respiratory disturbance index (RDI) and Sao2 drops. Posterior airway space was also a significant variable for RDI. Forced expiratory volume in one second, expressed as the percentage of forced vital capacity (FEV1/FVC), was significant when considering Sao2 drops. Upper airway abnormalities were also significant variables in the models and must be considered when treating OSAS patients.
Feline Oncornavirus-Associated Cell Membrane Antigen. V. Humoral Immune Response to Virus and Cell Membrane Antigens in Cats Inoculated With Gardner-Arnstein Feline Sarcoma Virus2
Authors: J. P. Schaller, M. Essex, D. S. Yohn, R. G. Olsen
Journal: JNCI Journal of the National Cancer Institute (1975)

Tumor growth responses in 5- to 6-week-old kittens inoculated with the Gardner-Arnstein strain of feline sarcoma virus exhibited three distinct pattern: 1) complete tumor regression or no detectable tumor growth in approximately one-third of 43 inoculated kittens, 2) rapid tumor progression which led to debilitation and death within 16.2 +/- 4.2 weeks following infection in an additional one-third, and 3) slow tumor growth or temporary regressions in the remaining third. The feline oncornavirus-associated cell membrane antigen (FOCMA) antibody response was closely correlated with tumor progression; rapid progressors had the lowest antibody titers, whereas those in the "no tumor or permanent regression" categories had the highest titers. These results agreed with those previously observed with another virus strain, the Snyder-Theilen feline sarcoma virus. Cats in the intermediate categories of tumor growth also had intermediate levels of FOCMA antibody. The presence of virus-neutralizing (VN) activity was not always correlated with anti-FOCMA activity. Animals in the rapid-progressor category, compared to the regressors or slow progressors, were more likely to have detectable VN antibody during early periods. Conversely, animals in the regressor group or group with no tumors were more likely to show an early rise in detectable anti-FOCMA activity than animals in either of the progressor groups.
Xpert MTB/RIF testing of pooled induced sputum
Authors: M.Y. Chew, J. Ng, V. Palanichamy, T.K. Lim
Journal: European Respiratory Journal (2014)

Some studies have suggested that Xpert MTB/RIF testing neither expedite pulmonary tuberculosis (PTB) treatment nor impact tuberculosis related morbidity in low and high disease burden settings. But this has not been evaluated in intermediate burden settings. We hypothesize that performing the Xpert MTB/RIF test on two induced sputa (IS) pooled together on the same day would improve diagnostic yield and impact treatment in symptomatic patients with active PTB. This is a prospective audit of adult patients suspected of PTB from June 2013 in a university hospital. In patients who were smear negative or unable to expectorate, 2 IS were collected and processed as one for acid fast bacilli, culture and Xpert. The reference standard for diagnosis of PTB was any positive culture. Patients were reviewed over 3 months. We report on the first 115 patients. PTB was diagnosed in 11/115(9.6%). Positive Xpert in pooled IS detected 5/11 (45%) cases. 3/5(60%) were smear, culture and Xpert positive. 2/5(40%) were smear negative, Xpert and culture positive. One smear negative, rifampicin resistant case was detected by Xpert. Additional 6 cases of PTB were detected from other respiratory specimens. All 11 patients were started on treatment on a positive smear and/or Xpert test the same day. Detection of rifampicin resistance resulted in the use of second line drugs. There were also 5 cases of non-tuberculous mycobacteria of which 4 were smear positive. Among these, 1 patient who had positive smear but indeterminate Xpert test received empirical PTB treatment. We conclude that there is a potential role for Xpert testing of pooled IS to improve diagnostic yield and expedite treatment in nearly half of new PTB cases.
The Australian asthma handbook: Practical and accessible guidelines for primary care
Authors: Helen Reddel, Naomi Fenton, Jenny Gowan, Jane Marr, Janet Rimmer, Peter van Asperen, Peter Wark, Siobhan Brophy, Jenni Harman, Mark Olszewski, Amanda Barnard
Journal: European Respiratory Journal (2014)

Clinical practice guidelines for asthma management in Australia were last published in 2006, as a 144-page print and pdf document ( Asthma Management Handbook , National Asthma Council Australia, Melbourne). Since then, there have been substantial changes not only in evidence but also in guideline methodology and online publishing.  Planning began with an online survey of guideline users (n=1071, 71% GPs). Over 80 primary care and specialist contributors formed the working groups and Guidelines Committee, chaired by a GP. An initial scoping review identified >350 clinical questions. Working groups developed recommendations using standardised methods, including systematic review (5 key clinical questions), examination of peer-reviewed evidence, adaptation of existing guidance, and consensus based on best-available evidence and clinical experience. Two independent experts reviewed the draft Handbook, and stakeholders including patient advocates and professional bodies were invited to comment.  The Handbook was published as an innovative, interactive website: www.asthmahandbook.org.au. Using a clear content hierarchy, recommendations (written as direct actions for primary practitioners), clinical decision pathways and summary tables were presented prominently, with more detailed information available at a deeper layer, and hyperlinks to all cited sources. A quick reference guide of the key advice and figures was printed.  Our experience has highlighted the value of involving primary carers in every aspect, to ensure practical and implementable guidelines for the local context. Feedback from reviewers and stakeholders indicates that the guidelines are perceived as innovative, comprehensive and clear.
Human Immunodeficiency Virus–Related Cancer in Children: Incidence and Treatment Outcome—Report of the Italian Register
Authors: D. Caselli, C. Klersy, M. de Martino, C. Gabiano, L. Galli, P.A. Tovo, M. Aricò
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To outline the incidence, presenting features, treatment response, and outcome of human immunodeficiency virus (HIV)–associated malignancies in infancy and childhood, together with the estimated risk of HIV-associated cancer in children born to mothers infected with HIV. PATIENTS AND METHODS: The Italian Register for HIV Infection in Children collected data by specific registration and follow-up forms. By March 1999, 5,060 children were recruited, including 4,889 with perinatal exposure to HIV-1. Overall, 1,331 infected children were enrolled onto the Register and classified according to current Centers for Disease Control criteria; of them, 1,163 were vertically infected (24% of those with perinatal exposure). Of these 1,163, 569 (49%) were considered to have been prospectively followed-up since they had been registered at birth or within the first 3 months of age. RESULTS: Of the 1,331 children observed for a median time of 6.5 years, 35 developed 36 malignancies, four of which occurred in patients with blood-borne risk. For the 1,163 vertically infected children, the cumulative number of years of observation was 7,178 child-years and the cumulative incidence of HIV-associated tumors was 4.18 per 1,000 children/yr (95% confidence interval [CI], 2.92 to 5.98). When only the 569 vertically infected children prospectively followed up since birth were considered, the cumulative number of years of observation was 2,803 child-years. In this group, 10 tumors were observed, with a cumulative incidence of HIV-associated tumors of 3.57 per 1,000 children per year (95% CI, 1.92 to 6.63). CONCLUSION: The risk of cancer was significantly higher but not restricted to symptomatic and/or immune-compromised children. Cancer-directed treatment should be given promptly to these patients, who have a fair chance to survive their tumor in view of potential highly aggressive antiretroviral therapy–associated improvement in survival and quality of life.
Inhaled corticosteroids and bone mineral density in children: A prospective 12-year follow-up study after early-life wheezing
Authors: Virpi Sidoroff, Mari Hyvärinen, Liisa Kröger, Heikki Kröger, Matti Korppi
Journal: European Respiratory Journal (2012)

Background: Inhaled corticosteroids (ICS) are the drugs of choice for asthma. Corticosteroids can have many detrimental effects on bone mineralization and growth, despite of inhaled administration.

Aims and objectives: To evaluate the association between the long-term use of ICS in childhood and bone mineral density (BMD) in teenagers.

Methods: Ninety-one children hospitalized for wheezing at age <24 months were prospectively followed until 12.2 (median) years of age. Data on ICS use were collected by interviewing the parents, supplemented by data from patient records. Cumulative doses, the duration of ICS use and systemic steroid doses were calculated. At the last check-up, BMD (BMDareal, g/cm2) was measured by dual energy X-ray absorptiometry (DXA) in 89 children, and apparent volumetric BMDs (aBMDvol, g/cm3) were calculated for the lumbar spine and femoral neck. Weight, height and pubertal stage were recorded.

Results: The regular use of ICS at age <6 years was associated with a lower BMDareal of the lumbar spine (mean 0.76, 95%CI 0.71-0.81 vs. 0.88, 0.84-0.92; p 0.006). A lower BMDareal and aBMDvol of the femoral neck were associated with higher cumulative doses of ICS at 0–12.2 (median) years of age. Pearson's correlation coefficients were r (r2) =-0.320 (0.10) for BMDareal and r (r2) = -0.291 (0.08) for aBMDvol. Age, sex and pubertal stage were significantly associated with both BMDareal and aBMDvol, but did not confound the results.

Conclusion: The use of ICS during childhood may be related to a decrease in BMD at early teenage, though the clinical manifestations of reduced BMD usually occur later in adulthood.
Moving towards clinically relevant preclinical models: Establishment, molecular characterization and in vivo evaluation of patient-derived low passage human tumor models
Authors: Michael Wick, Francis Nieves, Mitchell Moore, David Sidransky, Kyriakos Papadopoulos, Manuel Hidalgo
Journal: Clinical Cancer Research (2008)

A20  Standard human tumor xenograft models in preclinical oncology drug development typically originate from high passage number immortalized cell lines. While information from these models is useful in discovery and initial proof-of-concept studies, their clinical relevance is often limited due to alterations and adaptations from successive passages in tissue culture and animals. Preclinical models established from donor patient tumor fragments passaged only a few times in vivo may better represent clinical disease. In addition, genetic and molecular characterization of these models may aid in determining the models most useful for evaluating novel agents including targeted therapies.  We have developed the Tumorgraft™ platform, establishing low passage models of human cancer including lung, pancreas, colon, ovarian and gastric malignancies and various sarcomas. Following establishment, models were characterized at a molecular level using DNA and RNA-based assays. In addition, in vivo sensitivities of various agents were evaluated based on clinical information from patient donors as well as current standards of care.  Molecular characterization studies identified polymorphisms in some models, as well as known mutations in several signaling molecules important in cancer progression including the epidermal growth factor receptor (EGFR), B-raf, and Ras proteins. In vivo evaluation identified a range of activity towards standard agents tested, as well as clinically correlative drug sensitivities.  Overall, these low passage models offer an alternative to standard xenografts and may be more representative of clinical disease. Data collected from molecular characterization and in vivo evaluation of these models confirm their utility for development of novel agents especially targeted therapies.
Abstract 4368: MicroRNAs miR-503 and -182 regulate FBXW7 contributing to the malignant transformation to colon adenocarcinoma
Authors: Lihua Li, Aaron Sarver, Rohini Khatri, Praveensingh Hajeri, Iris Kamenev, Stephen Thibodeau, Clifford J. Steer, Subbaya Subramanian
Journal: Cancer Research (2014)

Abstract Progression from adenoma to colon cancer is a multi-step process and the role of microRNAs in this transformation is not completely understood. We used both in vitro and in vivo approaches to demonstrate the role of miRNAs in the transformation of adenoma to adenocarcinoma. Reporter assays were used to show the direct interaction of miRNAs to target gene. A Tet-inducible TripZ system and miRzips constructs were used in the in vitro function and xenograft studies. Kaplan-Meier survival curves and Cox regression were used to analyze the survival data in colon cancer patients. Here, we show that the combination of miR-503 and miR-182 contributes to the transformation of colon adenoma to adenocarcinoma by cooperatively regulating the tumor suppressor gene, FBXW7. We found that miR-182 was upregulated in both colon adenoma and adenocarcinoma, whereas miR-503 was upregulated only in adenocarcinoma, indicating a potential hierarchical and stepwise expression of these miRNAs in the regulation of FBXW7. Furthermore, we showed that colon adenoma derived non-tumorigenic AAC1 cells were transformative and tumorigenic in mice when expressing Tet-inducible miR-503. Finally, the combination of miR-503 and miR-182 transcript levels was predictive of poor outcome in colon cancer patients. We conclude that a step-wise expression of miR-182 and miR-503 in benign adenoma synergistically regulates the driver gene FBXW7, thus contributing to the progression of colon adenoma to adenocarcinoma. Citation Format: Lihua Li, Aaron Sarver, Rohini Khatri, Praveensingh Hajeri, Iris Kamenev, Stephen Thibodeau, Clifford J. Steer, Subbaya Subramanian. MicroRNAs miR-503 and -182 regulate FBXW7 contributing to the malignant transformation to colon adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4368. doi:10.1158/1538-7445.AM2014-4368