tbuckley/cabot-search huggingface dataset:
Cost-analysis of four diagnostic strategies for Pneumocystis carinii pneumonia in HIV-infected subjects
Authors: C Chouaid, B Housset, B Lebeau
Journal: European Respiratory Journal (1995)

The aim of this study was to analyse the cost-effectiveness ratio of four diagnostic strategies for Pneumocystis carinii pneumonia (PCP) in patients infected with human immunodeficiency virus (HIV). Two hundred and ten HIV-infected patients with suspected PCP underwent induced-sputum (IS) followed, if negative, by bronchoalveolar lavage (BAL); 85 of these patients were able to undergo an exercise test (ET), prior to induced sputum and BAL. The following strategies were analysed: BAL strategy (BAL whenever PCP is suspected); IS strategy (induced sputum followed by BAL if negative); exercise test (ET) strategy, (ET followed by BAL if the results are abnormal); and the ES (exercise sputum) strategy (i.e. BAL only after abnormal ET and negative IS). The cost of each strategy was calculated by taking into account only direct costs; the conditions in which two given strategies would be cost-equivalent were also evaluated. The prevalence of PCP in this population was 31%; IS had 100% specificity and 71% sensitivity, whilst ET had 100% sensitivity and 77% specificity. The costs of BAL, IS, ET and ES strategies were 210,000, 191,940, 140,700 and 112,700 FF, respectively. The ES strategy is, thus, most suitable for our unit. The most economic strategy depends not only on the cost and characteristics of the procedures, but also on the prevalence of PCP in the test population. In conclusion, we developed a model for use by diagnostic centres in choosing the most suitable strategy, on the basis of the local prevalence of PCP.
Sunitinib Treatment Exacerbates Intratumoral Heterogeneity in Metastatic Renal Cancer
Authors: Grant D. Stewart, Fiach C. O'Mahony, Alexander Laird, Lel Eory, Alexander L.R. Lubbock, Alan Mackay, Jyoti Nanda, Marie O'Donnell, Peter Mullen, S. Alan McNeill, Antony C.P. Riddick, Daniel Berney, Axel Bex, Michael Aitchison, Ian M. Overton, David J. Harrison, Thomas Powles
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The aim of this study was to investigate the effect of VEGF-targeted therapy (sunitinib) on molecular intratumoral heterogeneity (ITH) in metastatic clear cell renal cancer (mccRCC). Experimental Design: Multiple tumor samples (n = 187 samples) were taken from the primary renal tumors of patients with mccRCC who were sunitinib treated (n = 23, SuMR clinical trial) or untreated (n = 23, SCOTRRCC study). ITH of pathologic grade, DNA (aCGH), mRNA (Illumina Beadarray) and candidate proteins (reverse phase protein array) were evaluated using unsupervised and supervised analyses (driver mutations, hypoxia, and stromal-related genes). ITH was analyzed using intratumoral protein variance distributions and distribution of individual patient aCGH and gene-expression clustering. Results: Tumor grade heterogeneity was greater in treated compared with untreated tumors (P = 0.002). In unsupervised analysis, sunitinib therapy was not associated with increased ITH in DNA or mRNA. However, there was an increase in ITH for the driver mutation gene signature (DNA and mRNA) as well as increasing variability of protein expression with treatment (P &amp;lt; 0.05). Despite this variability, significant chromosomal and transcript changes to key targets of sunitinib, such as VHL, PBRM1, and CAIX, occurred in the treated samples. Conclusions: These findings suggest that sunitinib treatment has significant effects on the expression and ITH of key tumor and treatment specific genes/proteins in mccRCC. The results, based on primary tumor analysis, do not support the hypothesis that resistant clones are selected and predominate following targeted therapy. Clin Cancer Res; 21(18); 4212–23. ©2015 AACR.
Small-Molecule Bcl2 BH4 Antagonist for Lung Cancer Therapy
Authors: Bingshe Han, Dongkyoo Park, Rui Li, Maohua Xie, Taofeek K. Owonikoko, Guojing Zhang, Gabriel L. Sica, Chunyong Ding, Jia Zhou, Andrew T. Magis, Zhuo G. Chen, Dong M. Shin, Suresh S. Ramalingam, Fadlo R. Khuri, Walter J. Curran, Xingming Deng
Journal: Cancer Cell (2015)
Variation in Dialysis Facility Referral for Kidney Transplantation Among Patients With End-Stage Renal Disease in Georgia
Authors: Rachel E. Patzer, Laura C. Plantinga, Sudeshna Paul, Jennifer Gander, Jenna Krisher, Leighann Sauls, Eric M. Gibney, Laura Mulloy, Stephen O. Pastan
Journal: JAMA (2015)

Dialysis facilities in the United States are required to educate patients with end-stage renal disease about all treatment options, including kidney transplantation. Patients receiving dialysis typically require a referral for kidney transplant evaluation at a transplant center from a dialysis facility to start the transplantation process, but the proportion of patients referred for transplantation is unknown.To describe variation in dialysis facility-level referral for kidney transplant evaluation and factors associated with referral among patients initiating dialysis in Georgia, the US state with the lowest kidney transplantation rates.Examination of United States Renal Data System data from a cohort of 15,279 incident, adult (18-69 years) patients with end-stage renal disease from 308 Georgia dialysis facilities from January 2005 to September 2011, followed up through September 2012, linked to kidney transplant referral data collected from adult transplant centers in Georgia in the same period.Referral for kidney transplant evaluation within 1 year of starting dialysis at any of the 3 Georgia transplant centers was the primary outcome; placement on the deceased donor waiting list was also examined.The median within-facility percentage of patients referred within 1 year of starting dialysis was 24.4% (interquartile range, 16.7%-33.3%) and varied from 0% to 75.0%. Facilities in the lowest tertile of referral (<19.2%) were more likely to treat patients living in high-poverty neighborhoods (absolute difference, 21.8% [95% CI, 14.1%-29.4%]), had a higher patient to social worker ratio (difference, 22.5 [95% CI, 9.7-35.2]), and were more likely nonprofit (difference, 17.6% [95% CI, 7.7%-27.4%]) compared with facilities in the highest tertile of referral (>31.3%). In multivariable, multilevel analyses, factors associated with lower referral for transplantation, such as older age, white race, and nonprofit facility status, were not always consistent with the factors associated with lower waitlisting.In Georgia overall, a limited proportion of patients treated with dialysis were referred for kidney transplant evaluation between 2005 and 2011, but there was substantial variability in referral among facilities. Variables associated with referral were not always associated with waitlisting, suggesting that different factors may account for disparities in referral.
Cognitive Impairment in Survivors of Irradiated Brain Tumors Is Multifactorial: Implications of Polypharmacy With Antiepileptics?
Authors: Crispin T. Hiley
Journal: Journal of Clinical Oncology (2015)

randomized, placebo-controlled, phase III trial on the use of the anticholinesterasedonepezilforsurvivorsofirradiatedbraintumors.The chronic effects of radiation brain injury are characterized by a diffuse encephalopathy resulting in cognitive impairment. This vascular damage and the loss of neuroglial progenitor cells, particularly in the hippocampalarea,canhavearealeffectonthepost-therapycognitive functionofsurvivingpatients. 2,3 Icommendtheauthorsforconducting this study, which shows significant improvement in memory, motor speed, and dexterity for patients treated with a 24-week course of donepezil. Withparticularreferencetothe66%ofpatientsinthestudywith primary brain tumors, as radiation oncologists, fully appreciating the life-changing effects of cognitive impairment for long-term survivors causedbyourtreatmentcanbedifficult.Evenatpresentation,patients may already be experiencing cognitive impairment from the primary tumororaftersurgicalresection.Ouronlyinsightintothepremorbid functional level is often from the history provided by relatives or caregivers who may be present at the consultation. My perspective on thisissuehasbeenaffectedbyseeingtheeffectofchronicneurocognitive toxicity after diagnosis and treatment of a high-grade glioma in a friend and long-term survivor. Knowing the premorbid intellectual function in this case and the consequent neurocognitive impairment and detrimental effects on work, relationships, and family life has underscored to me the importance of survivorship.
Systemic inflammatory response in the weaning process from mechanical ventilation (VM) in COPD & non-COPD
Authors: Hugo Loureiro Koechlin, Jacobo Sellares, Miquel Ferrer, Mariano Rinaudo, Xavier Filellar, Rogelio Peralta, Silvia Terraneo, Antoni Torres
Journal: European Respiratory Journal (2013)

The aim of this study was to assess the changes in different parameters during weaning in a population of COPD & non-COPD ventilated patients and with SBTs of different duration. METHODS: A study was conducted in 93 patients under MV during weaning. Blood samples were drawn before, at the end of the SBT, at 2 hours and at 24 hours after the first trial. SBT lasted from 30-120 min. Samples were processed for the assessment of IL-1, IL-6, IL-10, IL-8, TNF-α and CRP. RESULTS: Patients were classified as COPD (n=41; failure = 14, success = 27) and non-COPD groups (n=52; failure=21, success=31). Baseline levels of markers before the SBT were similar in failure and success groups. COPD developed a higher increase of levels of CRP (p = 0.004), IL-6 (p = 0.005), IL-8 (p = 0.068) and TNF- α (p = 0.066) during a failed SBT compared to the success group. No changes were observed during the trial in non-COPD with SBT failure and success. In COPD, CRP increase during the SBT was significantly associated with increases in physiological parameters (fC, fR, BP, pH, PaCO2 and fR/Vt). The increase of CRP levels during the first SBT was significantly higher in COPD population who developed prolonged weaning (n = 7) compared to non-prolonged (p = 0.013). IL-8 levels during the SBT were associated with increased lengths of hospital stay, ICU stay and weaning. CONCLUSION Diverse markers increased during a failed SBT in COPD patients. The correlation between CRP and physiological parameters suggests that the cardiopulmonary stress during the SBT may explain the increase in these markers in COPD. More studies are needed to confirm the correlation of inflammatory markers levels with clinical outcomes.
Antibacterial therapy of community-acquired pneumonia (CAP) at patients with cardiovascular diseases (CVD)
Authors: Hanna Demchuk, Yuriy Mostovoy
Journal: European Respiratory Journal (2012)

To estimate antimicrobial therapy (AT) CAP at patients (PT) with CVD comparative study of 731 case histories of CVD patients (main age 62,0±12,0 years, 329 (45,0%) male) and 478 of patients (main age 32,2±13,4 yeas, 276 (57,7%) male) without concomitant diseases (WCD) hospitalized due to CAP during 2004-2006 was performed. Length of hospitalization was similar in both groups: CVD – 14,0±5,1 days and WCD – 13,8±4,7 days (p>0,1). 314 (42,9%) PT with CVD had risk of death by PORT score > 2,8%, but only 14 (2,9%) PT WCD had such risk (p 0,1). AT was ineffective at 156 (32,6%) WCD and at 211 (28,9%) CVD. Alternative AT was administered. Most of PT got monotherapy – 75,6% WCD and 82,9% CVD. Ciprofloxacin were prescribed 28,8% WCD and 25,1% CVD, gatifloxacin - 9,3% WCD and 4,6% CVD. 19,4% PT CVD got amicacin, but it did not have activity again main CAP pathogens. Cure came at 339 (65,8%) WCD and 399 (54,6%) CVD (p
Abcb1, ugt1a1 and oatp-c polymorphisms predict Irinotecan (CPT-11) toxicity
Authors: K. E. Rhodes, W. Zhang, D. Y. Yang, M. A. Gordon, A. M. Schultheis, F. Nagashima, S. Iqbal, H. Lenz
Journal: Journal of Clinical Oncology (2006)

3074 Background: Irinotecan (CPT-11), a topoisomerase I inhibitor, is approved for the use of both first- and second-line chemotherapy in metastatic colorectal cancer (CRC) patients. As of yet, only few reliable molecular markers have been identified for predicting CPT-11 toxicity. In this study, we tested specific gene polymorphisms that are known to be involved in the Irinotecan metabolic pathway: the ATP-binding cassette transporter subfamily (ABCB1, ABCG2 and ABCC2), carboxylesterase 1 (CES1), carboxylesterase 2 (CES2), uridine-diphosphoglucuronosyltransferase 1A1 (UGT1A1),hepatic organic anion transport protein (OATP-C) and cytochrome P450 (CYP3A4). Methods: We ran PCR-RFLP assays using genomic DNA from the blood of 54 advanced CRC patients treated with first-line 5FU/LV and CPT-11 at USC between 1999 and 2003. Results: Our cohort was comprised of 31 men (57%) and 23 women (43%) with a median age of 56 years (range: 34–77 years). Participants represented four ethnicities: 29 Caucasian (54%), 12 Asian (22%), 10 Hispanic (19%), and 3 African-American (6%). Three patients (6%) demonstrated complete response (CR), 20 patients (38%) showed partial response (PR), 24 patients (45%) continued with stable disease (SD), and six patients (11%) were found to have progressive disease (PD). One patient was invaluable for response data. Twenty-four patients (46%) experienced Grade 0–2 toxicity, while 29 (54%) experienced Grade 3–4 toxicity. One patient was inevaluable for toxicity data. The median progression-free survival was 10.9 months (95% CI, 7.6 to 12.1 months), and the median overall survival time was 27.9 months (95% CI, 21.3 to 56.6+ months) with median follow up of 30.0 months (range: 11.2 to 59.9 months). We found that the combination of at least one OATP-C 521 wild-type T allele, at least one ABCB1 1236 C allele and at least one UGT1A1*28 variant 7 repeat demonstrated a statistically significant association with Grade 3/4 toxicities (P=0.002, Fisher’s exact test). Conclusion: This is the first study to combine three independent gene polymorphisms within the same metabolic pathway in order to explain common CPT-11 grade 3–4 toxicity. [Table: see text]
High-dose therapy and autologous bone marrow transplantation in partial remission after first-line induction therapy for diffuse non-Hodgkin's lymphoma.
Authors: T Philip, O Hartmann, P Biron, J Y Cahn, F Pein, P Bordigoni, G Souillet, M Gartner, C Lasset, F Chauvin
Journal: Journal of Clinical Oncology (1988)

Seventeen patients received high-dose therapy with autologous bone marrow transplantation (ABMT) when in partial response after induction therapy. There were 11 children and six adults between 3 and 57 years old. Twelve patients were determined to have high-grade lymphoma (ten Burkitt's and two lymphoblastic), and five had intermediate-grade diffuse lymphoma. Ten patients had surgically proven active disease in the abdomen, two had active disease in the bone marrow, and five persistent neurological symptoms. The time interval between diagnosis and ABMT was 2-10 months (median 4 months). Two patients died of progressive disease and two others died while in complete remission (CR) because of toxicity. Thirteen of 17 are still alive and disease free with a median observation time of 2 years. Morbidity was high with 6/17 life threatening reversible complications but overall survival is 75% at 24 months in a group of patients clearly defined as having a very bad prognosis in previous studies.
Five consecutive cases of left bronchial transcervical video mediastinoscopic closure
Authors: Andrei Cristian Bobocea, Cristian Paleru, Olga Danaila, Adrian Istrate, Ioan Cordos
Journal: European Respiratory Journal (2011)

Objective:  The author reports the longest series of left bronchial transcervical closure using video-assisted mediastinoscopy, describing his experience with this technique and the particularities of the cases. Left bronchial closure as the first procedure of a two-step pneumonectomy for TB compromised lung is a rarely used technique.   Case report:  Five patients, mean age of 41.5 years, two females, three males, underwent videomediastinoscopic closure of the left main bronchi in the last 14 months, two for postpneumonectomy bronchopleural fistulas and three prior to pneumonectomy in TB destructed lung. The recovery was uneventful in every case, with the patients discharged the following day. The mean operative time was 55 min. No other incidents or procedure related complications were encountered. The three pneumonectomies followed at 3-4 weeks after the bronchial closure.   Discussions:  The mediastinoscopic bronchial closure is a novel option in highly selected patients. The positive factor influencing our decision were the virgin mediastinum. The dissection of the trachea through its natural route enables tracheal mobilization. It warrants minimal surgical trauma, and, if necessary, the bronchial stump has enough time to heal before the difficult pneumonectomy.   Conclusions:  Video-mediastinoscopy is an alternative to the open methods as it allows approaching the left main bronchi via the mediastinum. This technique is our choice because its specific morbidity is minimal compared with transpericardial sternotomy or a transthoracic approach. The mediastinoscopic approach is a novel option in highly selected patients in order to prepare and simplify a pneumonectomy.
Abstract 248: Comparison Of Transplantation Of Bone Marrow-derived Stem Cells, Adipose-derived Stem Cells And Endometrium- Derived Stem Cells In The Infarcted Heart
Authors: Xin Yang Hu, Kan Wang, Jian-an Wang
Journal: Circulation Research (2014)

Background: A variety of adult stem cells have been transplanted into the infarcted heart to cure myocardial infarction(MI), however, comparative studies are lacking to show more suitable source of cells for transplantation. Mesenchymal stem cells hold promise for myocardial regeneration therapy. Derivation of these cells from the endometrium tissue might be easier compared to bone marrow and adipose tissue. However,the in vivo fate of endometrium stem cells (EnSCs) in the infarcted heart has never been compared directly to mesenchymal cells derived from bone marrow(BMMSCs) and adipose tissue(AdMSCs). Methods: EnSCs, AdMSCs and BMMSCs were isolated from healthy donors were characterized using flow cytometry for surface markers identification and microscopy for cell morphology. They were characterized with β-actin promoter driving firefly luciferase and green fluorescent protein (Fluc-GFP) double fusion reporter gene, and were characterized using flow cytometry, bioluminescence imaging (BLI) and luminometry. Cell proliferation was tested by CCK-8 kit, colony forming unit(CFU) was stained by crystal violet staining and apoptosis ratio were detected by TUNEL assay. Rat (n=8/group) underwent myocardial infarction followed by intramyocardial injection of 5х105 EnSCs, AdMSCs and BMMSCs, or saline (negative control). Cell survival was measured using BLI for 6 weeks and cardiac function was monitored by echocardiography and hemodynamics analysis. Ventricular morphology was assessed using histology. Results: EnSCs, AdMSCs and BMMSCs were CD29+, CD90+, CD105+, shared similar morphology, but EnSCs had best proliferation, colony-forming and anti-apoptosis activity of 3 types of MSCs. Cells expressed Fluc reporter genes in a number-dependent fashion, as confirmed by luminometry. After cardiac transplantation, transplantation of EnSCs was better capable of preserving ventricular function and dimensions than others, as confirmed by echo test, PV-loops and histology. Conclusions: This is the first study comparing the in in vitro and in vivo behavior of 3 types of MSCs in the infarcted heart. AdMSCs and BMMSCs do not tolerate well in the cardiac environment, resulting in more cell death andworse cardiac function than EnSCs groups.
Expression of the small GTPase Rab27B is associated with stromal inflammation in ductal carcinoma in situ of the breast
Authors: M. Van Bockstal, K. Lambein, O. De Wever, H. Denys, G. Braems, R. Van den Broecke, V.F.J. Cocquyt, M. Bracke, L. Libbrecht, A. Hendrix
Journal: Annals of Oncology (2015)
Chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma: a radiation therapy oncology group study.
Authors: M al-Sarraf, T F Pajak, J S Cooper, M Mohiuddin, A Herskovic, P J Ager
Journal: Journal of Clinical Oncology (1990)

The results of radiotherapy alone for patients with locally advanced (stage III or IV) nasopharyngeal cancer (NPC) are poor in spite of the initial complete clearance. Twenty-seven patients (26 stage IV) were treated with concurrent standard radiotherapy and cisplatin 100 mg/m2 intravenously on day 1 and every 3 weeks for three courses. In 24 (89%) patients, complete response (CR) was achieved. The CR rate was higher for poorly undifferentiated cancer (100%). The major side effects were leukopenia (97%), anemia (54%), nausea and vomiting (81%), stomatitis (92%), and renal impairment (52%). Most of these side effects were either mild or moderate and reversible. All patients finished the radiotherapy dose (greater than 6,450 cGy), 19 (70%) had three courses of cisplatin, and eight had only two courses, six due to drug toxicity. Twenty-six patients with stage IV disease were compared with 78 patients treated with radiotherapy alone by the Radiation Therapy Oncology Group (RTOG). The disease-free survival (DFS), overall survival, and the incidence of distant organ metastasis appear to be better in the combined group. It was concluded that the combination of chemo-radiotherapy in patients with locally advanced NPC needs to be evaluated in a phase III randomized trial.
Calculation of outcome estimates for synchronous bilateral breast cancer patients using Adjuvant!
Authors: A. Nichol, C. Bajdik, R. Yerushalmi, C. Speers, M. L'Esperance, S. Tyldesley, K. A. Gelmon, I. Olivotto
Journal: Journal of Clinical Oncology (2008)

561 Background: The recognition of synchronous breast cancers is increasing because of improving screening and pretreatment imaging. For synchronous breast cancers, many clinicians choose adjuvant therapies by considering only the high-risk cancer, but cohorts of synchronous bilateral cases have worse outcomes than cohorts of unilateral cases. Adjuvant! outcome estimates for unilateral breast cancers have been validated by the Breast Cancer Outcomes Unit (BCOU) (Olivotto et al. JCO 2005;23:2716–25). Synchronous bilateral cases from the BCOU were used to investigate our hypothesis that synchronous breast cancer outcomes can be calculated by treating events from the two cancers as independent. Methods: All women < 75 years treated in British Columbia from 1989 to 1995 with new synchronous (< 2 months) bilateral breast cancers with sufficient staging information for Adjuvant! outcome estimates (pT1–3, pN0–3, M0, ER, grade, size, number of positive nodes, LVI, and treatment) were eligible. Our sample was 50 women of median age 65 (range 42–75). Researchers blinded to the clinical outcomes entered clinical and treatment (tamoxifen, type of chemotherapy) variables into Adjuvant! Online Version 8.0 with default comorbidity (Minor Problems) to obtain outcome estimates for each cancer for each patient. Using the unilateral estimates, bilateral estimates of overall survival (OS), breast cancer-specific survival (BCSS) and relapse-free survival (RFS) were calculated. Bilateral OS = Low Risk OS * High Risk OS / (100 - High Risk Die of Cancer). Bilateral BCSS = (100 - High Risk Die of Cancer - Bilateral OS). The bilateral RFS calculation accounted for contralateral recurrences in Adjuvant!. The mean for all patients was compared to the 10-year cohort outcomes. The study is descriptive. Results: Adjuvant! Low Risk breast cancer estimates were OS 79.2%, BCSS 92.0%, and RFS 81.9%. Adjuvant! High Risk breast cancer estimates were OS 64.8%, BCSS 75.8%, and RFS 63.7%. Clinical outcomes of the bilateral patient cohort were OS 58.0%, BCSS 72.0%, and RFS 62.0%. BCOU synchronous bilateral estimates were OS 58.3%, BCSS 69.5%, and RFS 62.2%. Conclusions: Our calculations of bilateral outcomes were better estimates of clinical patient outcomes than the commonly used unilateral High Risk estimates. No significant financial relationships to disclose.