tbuckley/cabot-search huggingface dataset:
Classification of lymph node metastasis for NSCLC: New classification based on the number of metastatic lymph node comparing to the current classification based on its location
Authors: H. Matsuguma, R. Nakahara, Y. Ishikawa, H. Suzuki, T. Kondo, Y. Kamiyama, S. Igarashi, K. Mori, T. Kodama, K. Yokoi
Journal: Journal of Clinical Oncology (2008)

7535 Background: Patients with resected stage IIIA-N2 NSCLC have been considered a heterogeneous group with regard to prognosis. Multiple station mediastinal lymph node metastases have been reported to be associated with poor prognosis compared to single station metastasis, and multiple station N1 disease has also been reported to be a poor prognostic factor. Because the number of metastatic nodes may be more critical than their locations, we hypothesized that a lymph node classification based on the number of metastatic nodes regardless of location would be simple and able to discriminate each prognostic group more effectively. Methods: Between 1987 and 2003, 574 patients with T1–2 NSCLC underwent complete resection of lung tumor with systematic nodal dissection without any preoperative treatment. Numbers of lymph nodes removed ranged from 4 to 66, and the average was 21. Twenty-eight patients had less than 10 lymph nodes removed, and we excluded these patients from further analysis. Numbers of metastatic lymph nodes ranged from 1 to 24, and the average was 3.7. The median follow-up period of surviving patients was 86 months. We developed a new lymph node classification simply based on the number of metastatic nodes regardless of its location, and compared this with the current AJCC-UICC lymph node classification combining with nodal station number. Results: The table shows the numbers of patients and 5-year survival rates at each nodal status stratified according to the current and new nodal classifications. The cutoff numbers in the new classification were determined to balance each nodal status in both classifications. Survival differences among each node status were larger using the new nodal classification than in the current classification. Conclusions: Lymph node classification based on the number of metastatic nodes can provide better discrimination of prognostic groups than the current classification based on location. Current N classification New N classification N status Number 5-y OS N status Number 5-y OS n0 348 73.2% n0 348 73.5% n1 104 53.2% n1 (1–2) 103 55.5% n2 96 40.8% n2 (3<) 97 37.9% Single station 54 44.0% n2a (3–5) 56 45.4% Multiple station 42 36.5% n2b (6<) 41 27.1% No significant financial relationships to disclose.
Phase I trial and pharmacokinetics (PK) of lenalidomide in pediatric patients with relapsed/refractory solid tumors or MDS: A Children’s Oncology Group phase I consortium study
Authors: H. Russell, M. S. Cairo, S. M. Blaney, P. C. Adamson, A. M. Ingle, S. Berg
Journal: Journal of Clinical Oncology (2008)

13532 Background: Lenalidomide (LEN) is approved for the treatment of adults with myelodysplastic syndrome and multiple myeloma. The mechanism of action is based on its immunomodulatory and anti-angiogenic effects. We report results from an ongoing phase I trial of LEN in children with recurrent or refractory solid tumors (ST) or myelodysplastic syndrome (MDS). Methods: Cohorts of 3 –12 children with ST received LEN by mouth once daily for 21 of 28 days at dose levels of 15, 20, 25, 30, 40, and 55 mg/m2/d. Children with MDS receive a fixed dose of 5 mg/m2/d. Plasma specimens for PK analysis were obtained with the first dose. Results: 38 pts with ST, median (range) 16 (4 –21) yrs of age, and 3 pts with MDS, median 7 (1–8) yrs, were enrolled; 33 ST pts and all MDS pts were fully evaluable for toxicity. At 15 mg/m2, 1/6 pts developed DLT (Gr 3 hypercalcemia). At 25 mg/m2 1 pt had a cerebrovascular ischemic event of uncertain relationship to LEN; future subjects were screened for thromboembolic risk factors prior to enrollment. At 40 mg/m2 3/12 pts developed DLTs (Gr 3 hypophosphatemia/hypokalemia; Gr 4 neutropenia/Gr 1 thrombocytopenia delaying the start of the next cycle for > 7 days; Gr 3 somnolence); at 55 mg/m2 1/6 pts developed DLT (Gr 3 urticaria). No pt with MDS had DLT. The MTD has not been reached on this study, but dose escalation will stop at the 70 mg/m2/d dose level. After one cycle no objective responses were observed. At 40 mg/m2/d (n=9), the apparent LNMD clearance was 150 ± 60 ml/min/m2 and half-life was 2.2 ± 1.4 hr. Conclusions: LEN is well tolerated at doses up to 55 mg/m2/d×21d with a 7 day rest in pediatric subjects in children with solid tumors. Drug disposition in children appears similar to adult patients. No significant financial relationships to disclose.
1-Antitrypsin deficiency {middle dot} 1: Epidemiology of 1-antitrypsin deficiency
Authors: M Luisetti
Journal: Thorax (2004)

Abstract The protein and molecular characteristics of variants of the α1-antitrypsin (AAT) gene are described, and available data on the genetic epidemiology of AAT deficiency are presented. α1-antitrypsin deficiencygenotypeisoelectric focusingpopulation screening
Potential role of ERBB-2 and cyclooxygenase-2 expression in human colon carcinomas
Authors: A. Antonacopoulou, A. Tsamandas, C. Skopa, D. Bonikos, H. Kalofonos
Journal: Journal of Clinical Oncology (2006)

3608 Background: ERBB2 receptor tyrosine kinase and cyclooxygenase-2 (COX-2) represent promising molecular targets for cancer therapy and/or prevention. This study investigates the relation between ERBB2 and COX-2 expression in human colon carcinomas. Methods: Immunohistochemistry to detect membranous ERBB2 and cytoplasmic COX-2 expression was performed on 124 archived human primary colon carcinomas and matched normal tissues. Results were expressed as % positive cells. In addition, the mRNA levels of ERBB2 and COX-2 were evaluated in a subset of the colonic tissue samples (46 tumor, 7 normal) using real time RT-PCR (expression relative to a calibrator) Results: The results are displayed in the table . ERBB2 and COX-2 expression was higher in well-differentiated tumors (p&lt;0.001 and p&lt;0.05, respectively). However, both ERBB2 and COX-2 protein levels increased in a statistically significant way towards more advanced stages. Linear regression revealed a strong positive correlation between ERBB2 and COX-2 expression in neoplastic populations (r=0.83, p=0.000082 for protein; r=0.411, p=0.00404 for mRNA). Thus, ERBB2 and COX-2 may transcriptionally regulate each other in colon carcinomas. Conclusions: Overexpression of ERBB2 and COX-2 may represent an early dysfunctional event in human colon carcinogenesis regarding tumor differentiation. However, their expression is increased in advanced stages. These markers may constitute important targets for chemoprevention or adjunct therapy of well-differentiated colon carcinomas. [Table: see text] No significant financial relationships to disclose.
Octreotide (Oct) Lar Reconstituted in a New Vehicle (Nv): Phase 1, Open-Label, Randomized, Bioequivalence Study Vs Oct Lar 30 Mg (Current Vehicle)
Authors: S. Sarp, K. Roessner, A. Brueck-Scheffler, A.P. Tripathi, J. Roberts
Journal: Annals of Oncology (2014)
Aspirin does not reduce the clinical benefits of the mineralocorticoid receptor antagonist eplerenone in patients with systolic heart failure and mild symptoms: an analysis of the <scp>EMPHASIS‐HF</scp> study
Authors: Ken Lee Chin, Timothy J. Collier, Bertram Pitt, John J.V. McMurray, Karl Swedberg, Dirk J. van Veldhuisen, Stuart J. Pocock, John Vincent, Eva Turgonyi, Faiez Zannad, Henry Krum
Journal: European Journal of Heart Failure (2016)
Estrogen receptor expression and efficacy of docetaxel in early breast cancer: A pooled analysis of 3,490 patients included in two randomized trials
Authors: F. Andre, K. Broglio, H. Roche, M. Martin, F. Penault-Lorca, G. N. Hortobagyi, D. A. Berry, L. Pusztai
Journal: Journal of Clinical Oncology (2007)

537 Background: It has been suggested that estrogen receptor (ER) expression is associated with relative resistance to adjuvant chemotherapy. The efficacy of adjuvant chemotherapy is still matter of controversy in this subset of patients. The aim of the present study was to assess the efficacy of docetaxel according to ER expression in adjuvant treatment trials. Patients and Methods: The efficacy of docetaxel according to ER expression was assessed in a pooled analysis of two randomized studies (BCIRG001 and PACS01) that included overall 3,490 patients with axillary node positive breast cancer. These studies compared either 3 (PACS01) or 6 (BCIRG001) cycles of a docetaxel-containing regimen, to a chemotherapy that did not contain docetaxel. Hazard ratios (HR) for death were determined by a Cox model adjusted for clinical characteristics (age, T size and number of lymph node involved). Interaction between docetaxel efficacy and ER expression was tested. Results: ER status was assessable in 3,329 patients (95%). The median age was 49 years old (range, 23–70). ER was expressed in 2,493 tumors (74%). In patients with assessable ER status (n=3329), docetaxel was associated with a significant reduction in the risk of death (HR=0.69; 95%CI: 0.51–0.92, p=0.01). Docetaxel therapy was associated with a 30% reduction in the risk of death in ER-positive disease (HR=0.70; 95%CI: 0.54–0.91) and a 31% reduction in the risk of death in ER-negative disease (HR=0.69; 95% CI: 0.52–0.94). Test for interaction did not detect any statistically significant difference in the relative effect of docetaxel according to ER status (HR for interaction=1.03; p=0.87). Conclusion: In this pooled analysis of two randomized trials, the relative effect of docetaxel on overall survival in adjuvant setting was not different between ER-positive and ER-negative disease. Docetaxel was associated with a significant risk reduction of death in patients with ER-positive disease. No significant financial relationships to disclose.
Cell Killing, Kinetics, and Recovery Responses Induced by 1,2:5,6-Dianhydrogalactitol in Dividing and Nondividing Cells In Vitro2
Authors: S. C. Barranco, D. R. Flournoy
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Cell Killing, Kinetics, and Recovery Responses Induced by 1,2:5,6-Dianhydrogalactitol in Dividing and Nondividing Cells In Vitro Get access S. C. Barranco, S. C. Barranco Search for other works by this author on: Oxford Academic PubMed Google Scholar D. R. Flournoy D. R. Flournoy Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 3, March 1977, Pages 657–663, https://doi.org/10.1093/jnci/58.3.657 Published: 01 March 1977 Article history Received: 19 April 1976 Accepted: 23 August 1976 Published: 01 March 1977
Abstract 17246: Echocardiographic Predictors of Response to Cardiac Resynchronization Therapy and Subsequent Events
Authors: Jae Hyeong Park, Richard A Grimm, Zoran B Popovic, Thomas H Marwick
Journal: Circulation (2012)

Background:  We hypothesized that scoring with echocardiographic parameters can be used to predict good response after cardiac resynchronization therapy (CRT).   Methods:  We enrolled total 334 consecutive pts (224 men, mean 65±12 y) with interpretable echo who underwent CRT from Feb 2005 to Aug 2007 and had follow-up echocardiography. Global longitudinal strain (LVGLS) was measured using the average of 3 apical images and time delay of septum to lateral LV wall was calculated with velocity vector imaging. Regression analysis was performed to evaluate factors associated with reverse remodeling (defined as >15% reduction in the LV end-systolic volume within 1 year after CRT) and to create a response score.   Results:  During the follow-up period (57±22months), 134 deaths, 18 heart transplantations/VAD implantations and 93 hospital admissions occurred, and 161 pts (48%) showed reverse LV remodeling. Three independent echocardiographic factors were identified LV end-diastolic dimension index  2 , LVGLS  35%. Combination into a score showed a score >3 (range, 0-4) predicted LV reverse remodeling with a sensitivity of 85% and specificity 76%. Cox proportional hazard regression analysis showed a 27% ( P    Conclusion:  A multiparametric echocardiographic score is helpful in selecting pts likely to reverse remodel with CRT, and predicts clinical outcomes.
Evaluation of T1-mapping magnetic resonance imaging for the detection of chronic lung allograft dysfunction
Authors: Julius Renne, Peer Lauermann, Jan Hinrichs, Christian Schönfeld, Sajoscha Sorrentino, Marcel Gutberlet, Peter Jakob, Axel Haverich, Gregor Warnecke, Tobias Welte, Frank Wacker, Jens Gottlieb, Jens Vogel-Claussen
Journal: European Respiratory Journal (2014)

Background

Bronchiolitis obliterans syndrome (BOS) is the major limiting factor for long-term survival after lung transplantation. However, markers for the detection of initial stages are missing.

Aims and objectives

T1 mapping MRI of the lungs is evaluated for the detection of chronic lung allograft dysfunction in patients following double-lung transplantation.

Methods

Fifty-one double-lung allograft recipients were included and gave written informed consent. BOS was classified with spirometry and patients were divided into three groups: BOS 0, BOS0p and late stages (BOS1-3). Coronal T1 maps of the lungs were acquired at room air and 100% oxygen using an inversion recovery snapshot fast low angle shot sequence at 1.5 T. The coefficient of variation for T1 values under room air as well under oxygen and the oxygen transfer function (OTF) were calculated (Jakob et al., Magn Reson Med 2004).

Results

The coefficient of variation for T1 values was significantly higher for BOS 1-3 patients on both the room air (p=0.007) and the oxygen T1 maps (p=0.002) compared to patients with BOS 0 status. The OTF showed a strong trend towards decreased values in the groups with increasing CLAD/BOS stages (p=0.07).

![Figure][1] 



Conclusions

The heterogeneity of T1 values as well as the OTF may be used for early detection of BOS and should be evaluated in future prospective trials.

 [1]: pending:yes
Helicobacter pylori eradication in gastric MALT lymphoma: Results of 316 patients treated inside and outside of a clinical trial
Authors: T. Wündisch, A. Günther, C. Mösch, M. Huynh, M. Stolte, A. Neubauer
Journal: Journal of Clinical Oncology (2006)

7584 Background: Cure of infection induces remissions in most patients with early stage Helicobacter pylori- (Hp-) positive gastric MALT (mucosa-associated lymphoid tissue) lymphoma (GML). We compared the long-term outcome of 120 patients treated within a multicenter trial to that of 196 routinely treated patients. Methods: 120 patients with stage I1E disease from a prospective trial (cohort 1) were compared to 196 patients with GML treated outside a trail by sole Hp-eradication (cohort 2). The latter were evaluated in retrospect and only a minority had a complete staging at diagnosis. Histology was the standard for remission evaluation in all patients and performed by the same pathologist (MS). B-cell-clonality and the t(11;18) were assessed in cohort 1-patients. Results: Median endoscopic follow-up was 79 months (range, 1–121) in cohort 1-patients and 27 months (range, 0–120) in cohort 2-patients. In 41% of the cohort 2-patients no or one control endoscopy was performed after a first CR. Most patients are in continuous complete histological remission in both cohorts. 3 cohort 1- and 5 cohort 2-patients relapsed. 16 cohort 1- and 13 cohort 2-patients exhibited histological residual disease (RD) during follow up after a first CR; a watch-and-wait strategy was applied, and most entered into a second CR. Conclusions: Hp-eradication results in long term CR in the majority of patients with GML in both cohorts. Duration of remission, rate of relapse, and RD were similar, regardless of incomplete staging and follow-up procedures and higher age in the cohort 2-patients. No significant financial relationships to disclose.
The Bedford Survey: a critique of methods and findings.
Authors: Keen H
Journal: Journal of the Royal Society of Medicine (1964)

This article presents a critical analysis of the methods and findings of the Bedford Survey the aim of which was to identify undiagnosed diabettics in the population.  The results indicate the insensitivity of the postprandial urine test for sugar as a preliminary screening procedure.  Wheareas about 15% of the survey population should have demonstrated capillary blood sugar levels of 120 mg/100 ml or more 2 hours after 50 gm of glucose by mouth only 1% fell into this range.  Moreover a 4% incidence of glycosuria under survey conditions rose to 30% in a urine retest after the 50gm glucose load at glucose tolerance test.  The occurrence of raised 2-hour blood sugar levels at glucose tolerance test among glycosurics and nonglycosurics was greater among women than men and rose with increasing age.  It is assumed that as age advances increasingly high levels of blood sugar are required to produce glycosuria; however the level required is higher in women than in men at all ages.  Although sensitivity may be improved by testing the urine after a standard 50 gm load this procedure yields many false positive results.  Direct blood sugar measurement after a glucose load is the screening device of choice.  These findings further indicated the existence of a sizable number of people with marginal elevation of blood sugar levels who are not readily assignable to either diabetic or normal categories.  Not only may these individuals be candidates for the development of symptomatic diabetes but the widespread distribution of arterial disease and cataract in the population may be related to an unrecognized borderline diabetic state.  This suggests a need for careful evaluation of such people through controlled trials of treatment.  Those with 2-hour blood sugar values in the intermediate range (120-199 mg/100 ml) are being seen at a special borderline clinic in Bedford where they are randomly allocated to treatment groups and given regular eye kidney peripheral nerve and blood vessel examinations.  Analysis of data from this program is expected to determine whether there is a critical level of blood sugar at which diabetic damage starts and if so whether treatment can postpone or prevent damage.
Kidney tuberculosis in last century and now – Is it the same disease?
Authors: Denis Kholtobin, Ekaterina Kulchavenya
Journal: European Respiratory Journal (2011)

Kidney tuberculosis (KTB) has non-specific clinical features and mimics on different other urological diseases: urolithiasis, cancer, pyelonephritis, cystitis etc. Moreover clinical features are not stable for ages, they change rather quickly.  The aim was to compare KTB in Siberia in 1980-1990 (1st group, 268 patients) and in 2000-2005 (2nd group, 227 patients), all were in-patients of Urogenital Department of Novosibirsk Research TB Institute.  A flank pain in 1st group was rarer (58.9% and 72.8% accordingly), but frequency of dysuria was the same (57.1% and 54.3%). Frequency of renal colic decreased from 16.1% up to 12.3%; haematuria increased from 30.4% up to 48.1%. Pyuria left most common laboratory sign – 91.7 – 91.4%. Significantly reduced a frequency of positive cultures – mycobacteriuria was revealed in 84.5% in first group and in 44.0% only in novo days.  Asymptomatic course was about equal – 8.9% and 6.2%, but frequency of acute debut changed significantly. In 1st group 34.5% patients got sick acutely, with manifesting clinical features, fever, pain etc. In second group the same patients there were 4.9% only. On contrary, obscure, vogue symptoms were in 56.6% in 1st group and in 88.9% - in 2nd group.  Mean age was stable: 40.5 in 1st group and 43.8 in 2nd group. A rate male: female was about 2:3 in both groups.   Conclusion:  We can speak about clinical pathomorphosis of KTB. Clinical features of KTB has changed in last years. In 7 times rarer became acute onset of KTB, significantly more often patients have flank pain and haematuria now. Asymptomatic course of KTB is possible too. All this may be a reason for late diagnosis.
Use of somatostatin receptor PET to differentiate between high-risk and low-risk atherosclerotic lesions: a prospective clinical study
Authors: Jason M Tarkin, Francis R Joshi, Nicholas R Evans, Ashley M Groves, Deepa Gopalan, Roie Manavaki, Peter J Kirkpatrick, Patrick A Coughlin, John R Buscombe, Tim D Fryer, Martin R Bennett, Anthony P Davenport, Elizabeth A Warburton, James H F Rudd
Journal: The Lancet (2016)
The effects of<i> SLCO1B3</i>, <i>ABCG2</i>, <i>MDR1, </i>and <i>CYP3A5</i> single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of docetaxel in nasopharyngeal carcinoma patients.
Authors: S. Chew, H. Li, O. Singh, W. T. Lim, E. Tan, J. Lee, B. Chowbay
Journal: Journal of Clinical Oncology (2010)

e13569 Background: This exploratory study aimed to explain the interindividual variabilities of docetaxel pharmacokinetics and pharmacodynamics through the genotyping of SLCO1B3, ABCG2, MDR1, and CYP3A5. Methods: Sixty Asian patients with metastatic nasopharyngeal carcinoma (NPC) receiving docetaxel (median age: 49.7 years; range 25.4-67.8) were recruited. Docetaxel was administered over 1-hour on days 1, 8, and 15 every 28 days at 30mg/m2/dose for a total of 6 cycles. Genomic DNA was isolated from the peripheral blood samples and genotyped for SLCO1B3, ABCG2, MDR1, and CYP3A5 polymorphisms. The incidences of treatment-related toxicities were recorded. Docetaxel pharmacokinetic parameters were estimated by non-compartmental modeling and genotypic-phenotypic correlations were carried out. Results: Pharmacokinetics of docetaxel was significantly affected by three intronic polymorphisms of SLCO1B3. The Cmax was found to be significantly different among patients containing different genotypes at IVS3+76G>A (p= 0.0094), IVS6-76T>C (p= 0.0016) and IVS12+55C>T (p= 0.042). Additionally, the AUC0-inf and clearance in patients were also influenced by IVS6-76T>C (p=0.029 and 0.026 respectively). No correlations were noted between ABCG2, MDR1, and CYP3A5 variants and docetaxel pharmacokinetics. With regards to toxicities, patients harboring different genotypes at –1390A>G of SLC01B3 tended to have different grade of toxicities in terms of fatigue (p= 0.035), hemoglobin (p= 0.016), and SGPT (ALT) (p= 0.017). SGPT (ALT) was also found to be different among patients with different genotypes at 1056G>A (p= 0.025) and - 991G>A of SLC01B3 (p=0. 0017). Patients carrying the ABCG2 34G>A polymorphism also had significantly different grades of fatigue (p=0.041). Conclusions: This study suggests that functional polymorphic variants in SLCO1B3 and ABCG2 genes might be potentially responsible for the large interindividual differences in docetaxel pharmacokinetics and pharmacodynamics in NPC patients. No significant financial relationships to disclose.