tbuckley/cabot-search huggingface dataset:
Using the lower limit of normal to classify lung disease misses at risk people
Authors: David Mannino, Enrique Diaz
Journal: European Respiratory Journal (2011)

Background:  The Global Initiative on Obstructive Lung Disease (GOLD) stages for chronic obstructive pulmonary disease (COPD) uses a fixed ratio of the post-bronchodilator forced expiratory volume in one second (FEV1)/ forced vital capacity (FVC) of 0.70 as a threshold to define obstruction. Some advocate using lower limit of normal (LLN) for the FEV1/FVC ratio, FEV1, and FVC to define abnormality.   Objective:  To determine mortality in a representative sample of the U.S. adult population comparing abnormality determined using GOLD criteria to that determined using LLN criteria.   Methods:  We used baseline data from the Third National Health and Nutrition Examination Survey (NHANES III) and follow-up mortality data. We classified subjects as obstructed, restricted, or normal based on the GOLD vs. the LLN criteria. We used Cox proportional hazards models to determine the relation between diagnosed lung disease and mortality, adjusting for covariates.   Results:  Our study sample included 13,847 subjects, of whom 3,774 died during the follow-up period. Of subjects classified as obstructed and restricted using GOLD criteria, 20.9% and 18.0% were classified as normal using the LLN. Mortality was increased in the obstructed (hazards ratio [HR] 1.48, 95% confidence interval [CI] 1.21, 1.80) and restricted (HR 2.03, 95% CI 1.67, 2.45) subjects classified as normal using the LLN, but abnormal using the GOLD criteria.   Conclusion:  In the nationally representative NHANES III data, subjects classified as normal using the LLN criteria but obstructed or restricted using the GOLD criteria have a higher risk of mortality.
Design of an ongoing randomized study on the long-term safety and efficacy of darbepoetin alfa (DA) administered 500 mcg every three weeks (Q3W) to non-small cell lung cancer (NSCLC) patients (pts) with anemia concomitant with chemotherapy (ACC).
Authors: P. Gascon, D. H. Henry, A. Fleishman, J. E. Borenstein
Journal: Journal of Clinical Oncology (2010)

TPS325 Background: Erythropoiesis-stimulating agents (ESAs) such as DA are approved for treating ACC based on controlled studies showing ESAs can raise hemoglobin (Hb) and reduce transfusions. In several controlled ACC studies in pts with small cell lung cancer or NSCLC (JCO. 2008;26:2342-49; JNCI. 2002;94:1211-20), ESAs had a neutral impact on mortality and disease progression. However, ESAs were reported to increase mortality and/or progression in some other tumor types examined in studies with high Hb targets and in one NSCLC study of pts not receiving chemotherapy or radiotherapy (JCO. 2007;25:1027-32). Since lung cancer pts often develop ACC, further studies on ESA use in these pts are warranted. We describe here a randomized trial (Amgen 20070782; ClinicalTrials.gov NCT00858364) currently enrolling to study the long-term safety of DA in NSCLC pts with ACC. Methods: Up to 500 clinical sites in ∼34 countries are targeted for this study. Pts (∼ 3000) will be randomized 2:1 to DA (500 mcg) or placebo Q3W until progression or end of chemotherapy. Key eligibility criteria include ≥ 18 years, advanced NSCLC, first-line chemotherapy, ECOG status ≤ 1, and screening Hb ≤ 11 g/dL. At Hb > 12 g/dL, study drug administration will be withheld until Hb is ≤ 12 g/dL. Noninferiority of ESA to placebo for overall survival (primary endpoint) and progression-free survival (modified RECIST per investigator; secondary endpoint) will be examined when 2700 deaths occur. Other safety endpoints include tumor response and thromboembolic events. Transfusion rates are a key efficacy endpoint; Hb changes will also be reported. This global study will likely take a year to obtain protocol approvals from all countries and to initiate study procedures at all clinical sites; 5 countries have screened pts as of December 2009. This trial aims to provide comprehensive data on whether DA affects survival, disease progression, and reduces transfusions in NSCLC pts with ACC. A better understanding of the DA benefit:risk profile in ACC may provide further global guidance for ESA use in medical practice. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen Amgen
Hypercholesterolemia Abolishes High-Density Lipoprotein–Related Cardioprotective Effects in the Setting of Myocardial Infarction
Authors: Gemma Vilahur, Manuel Gutiérrez, Laura Casaní, Judit Cubedo, Antoni Capdevila, Guillem Pons-Llado, Francesc Carreras, Alberto Hidalgo, Lina Badimon
Journal: Journal of the American College of Cardiology (2015)
Effectiveness of treatment of transdermal narcotics in rib fractures
Authors: Okan Solak, Hidir Esme, Kubilay Ocalan, H. Volkan Kara, Nuri Tutar
Journal: European Respiratory Journal (2011)

Rib fracture is the most common pathology in thoracic traumas. Severe pain is the most common symptom. The use and dosage of narcotic analgesics in the early period is controversial. Our aim is to investigate the efficacy of transdermal release (TR) narcotics in these patients

There were consequtive 25 patients who had diagnosis of rib fractures. Patients in group 1 (n=10) had intercostal nerve block (by bupivacain 0.5%), intramuscular narcotic (meperidine) according to the weight of the patient and paracetamol per orally. Patients in group 2 (n=15) intercostal nerve block (by bupivacain 0.5%), transdermal release (TR) narcotics (fentanyl) and paracetamol orally. We used Visual Analog Scale (VAS) for scoring the pain. The efficacy of treatment is evaluated by calculation and scoring of VAS both at exertion and relaxation.The sedation that might be by the narcotic agents was followed by Ramsey Sedation Scale (RSS) and arterial blood gases. The study was ended in the fifthy day.

There were no difference for age, gender, type of trauma, additional pathology number of fractured ribs and their localization between the two groups. Both groups had improvement for VAS before and after treatment. The VAS improvement in group 2 was better in both in relaxation and activity for the 5 days

It is difficult to establish the effective blood levels of parenteral narcotics so that there is continous need for repetative administration of the drugs. In TD applied narcotics the blood levels of the drugs are stable. The use of narcotics transdermally instead of paranteral administration was more effective and comfortable by the way of administration according to our study results.
Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report.
Authors: J C Yang, S L Topalian, D Parkinson, D J Schwartzentruber, J S Weber, S E Ettinghausen, D E White, S M Steinberg, D J Cole, H I Kim
Journal: Journal of Clinical Oncology (1994)

PURPOSE A randomized prospective study was performed to compare the efficacy and toxicity of high-dose intravenous bolus interleukin-2 (IL-2) and a lower-dose intravenous bolus regimen for the treatment of metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS Between March 1991 and April 1993, 125 patients with metastatic RCC were randomized to receive IL-2 by intravenous bolus every 8 hours at either 720,000 IU/kg (high-dose) or 72,000 IU/kg (low-dose) to the maximum-tolerated number of doses (or a maximum of 15 doses). After approximately 7 to 10 days, both treatment groups were re-treated with a second identical cycle of therapy. Those patients who were stable or responding to treatment 5 to 6 weeks later went on to receive re-treatment with another course (two cycles) of therapy. Response rates and toxicity were determined for the two treatment arms. RESULTS One hundred twenty-five patients received a total of 208 courses of therapy. Sixty patients were randomized to receive low-dose, and 65 to receive high-dose IL-2. There were no treatment-related deaths in either arm. There was a greater incidence of grade III or IV thrombocytopenia, malaise, and hypotension in patients who received high-dose IL-2, while patients who received low-dose IL-2 had significantly more infections. Three percent of treatment courses with low-dose IL-2 required vasopressor support, compared with 52% of courses with high-dose IL-2. Patients who received low-dose IL-2 had a 7% complete response (CR) and an 8% partial response (PR) rate, and patients who received high-dose IL-2 had a 3% CR and a 17% PR rate. CONCLUSION Low-dose intravenous bolus IL-2 represents an effective regimen for the treatment of metastatic RCC, with preliminary results comparable to those observed with high-dose IL-2. Low-dose IL-2 can be administered with significantly fewer complications, reduced use of vasopressor support, and fewer admissions to an intensive care unit (ICU).
Management of N3 stage IIIB NSCLC: Changes in US physician behavior following ASCO 2007
Authors: M. R. Green, H. West, M. A. Socinski, J. Willey, L. Daniels, K. Lemke, G. Rafferty, L. Iovino
Journal: Journal of Clinical Oncology (2008)

7579 Background: Nearly all non-operative treatment approaches to “fit” patients with stage III NSCLC include both chemotherapy (CT) and radiation (TRT). In the US the most common strategies include concurrent (C) CT/TRT. Many patients also receive additional CT, either as “induction (Ind)” or “consolidation (Cons)”. NMCR data, derived between 1/05 and 5/07 from nearly 1,000 US oncologists showed 69% favored immediate C CT/TRT followed by additional CT Cons. For 50% the additional CT was Q 3 week docetaxel. For the other 19% it was 2 additional cycles of the same CT used during C CT/TRT. At ASCO ‘07, Hanna et al. (abst # 7512), presented Hoosier Oncology group (HOG) phase III data that failed to show either a median or overall survival advantage for the addition of Cons docetaxel after concurrent, full-dose, etoposide-cisplatin-radiation (EC/TRT) compared to EC/TRT alone. Methods: We used 2 different case-based assessments to quantitate plans of American oncologists for using Cons therapy for patients with N3 stage IIIB NSCLC. Series 1 focused on non-operative management and included 427 MD participants (N = 427), queried either pre or post ASCO. The 2nd (N = 331), occurring post ASCO, included a potential surgical strategy as well. Results: Series 1: Progressive post-ASCO shift away from CT/TRT combined with additional CT as either Cons or Ind. Additional CT: Pre ASCO 84% (Cons 67%); Post ASCO 61% (Cons 51%). C CT/TRT alone rose from 10% pre ASCO to 35% post ASCO, including 58% of 73 consultants studied in late 9/2007. Series 2: 25% selected a surgical component of Rx, 46% planned Cons, 22% opted for C CT/TRT alone, and 10% Ind CT followed by CT/TRT. Conclusions: A data driven shift away from Cons or Ind CT is occurring in management of N3 stage IIIB disease. However physicians are cautious about modifying practice after a single ASCO presentation. At ASCO ’08 we will present the full case scenarios used and a detailed analysis of both data sets, including consultant demographics and segmented time trends, to further define the impact of recent data on physician management patterns. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration NMCR Analytics NMCR Analytics
A retrospective review of metastatic or recurrent uterine sarcomas treated with paclitaxel, carboplatin, and gemcitabine chemotherapy
Authors: D. Gibbon, A. Wagreich, W. Nieves-Neira, W. Shih, W. Ziang, L. Rodriguez-Rodriguez, J. Germino
Journal: Journal of Clinical Oncology (2004)

5143 Background: The prognosis of metastatic uterine sarcoma is poor with median survival reported between 4–26 months. The primary objective of this study was to assess the activity of paclitaxel, carboplatin and gemcitabine (GCP) in the treatment of primary, metastatic, or recurrent uterine sarcomas. Methods: This retrospective study was given an exemption by the Institutional Review Board at Robert Wood Johnson University Hospital. The efficacy of the GCP regimen in women with metastatic or recurrent uterine sarcomas was assessed. Patients were treated on a phase II soft tissue sarcoma protocol or off protocol by the gynecologic oncology division. Results: 13 patients were treated, 9 on and 4 off protocol. 4 patients were inevaluable; 3 patients for less than one month of therapy and 1 patient without measurable disease. Histology included 6 leiomyosarcomas (LMS), 1 endometrial stromal sarcoma (ESS), and 2 carcinosarcomas (CS). There was one 9 month complete response (11%) (LMS) pt remains NED, one 10 month partial response (11%) (CS), 4 patients (44%) with stable disease (3 LMS, 1 ESS), and 3 patients with progressive disease (33%) (2 LMS, 1 CS). The overall response rate was 22%. The duration of stable disease ranged 5 to 22.8 months. Median time to progression for all patients was 10 months (95% CI {83 –530 days}). The median overall survival was 36.6 months. GCP was discontinued in one patient for grade 3 GI toxicity and paclitaxel was discontinued in one patient for grade 2 neuropathy. Toxicity included grade 3 neutropenia (5), grade 3 anemia (1), and grade 3 GI toxicity (1). There were no hospitalizations required secondary to toxicity. Conclusions: GCP combination chemotherapy demonstrates moderate activity, with acceptable toxicity, in patients with advanced uterine sarcomas. Given the durable median time to progression and overall survival, this pilot data supports the evaluation of this regimen in a multi-institutional phase II study. No significant financial relationships to disclose.
Guanylyl cyclase C integrates metabolic and proliferative programming opposing intestinal tumorigenesis through AKT
Authors: Jieru Lin, Adam Snook, Peng Li, Stephanie Schulz, Giovanni Pitari, Scott Waldman
Journal: Cancer Research (2008)

LB-279  Guanylyl cyclase C (GCC), the intestinal receptor for the paracrine hormones guanylin and uroguanylin whose early loss is universally associated with initiation of colorectal cancer, has emerged as a tumor suppressor whose dysregulation promotes proliferation and produces genomic instability underlying intestinal neoplasia. Beyond corruption of replicative and genomic integrity, reprogramming of metabolic circuits confers a survival advantage to cancer cells globally licensing tumor initiation and progression in all tissues. Here, we show that GCC is a systems integrator, coordinating glycolytic and oxidative metabolism with proliferation underlying normal regenerative homeostasis along the crypt-surface axis, and opposing tumorigenesis, in intestine. Eliminating GCC signaling in mice expands the proliferating crypt compartment, accelerating the cell cycle by inducing critical mediators including cyclin D and phosphorylated Rb. Replicative induction is coupled with an increase in glucose transport and the glycolytic machinery and a reciprocal reduction in mitochondrial biogenesis and oxidative phosphorylation, recapitulating the neoplastic metabolic phenotype defining a tumorigenic niche. Conversely, GCC signaling reverts neoplastic proliferative and metabolic programming in human colon cancer cells, decelerating the cell cycle and switching from glycolytic to mitochondrial ATP production, reminiscent of normal enterocytes. Coordination of proliferative and metabolic circuits in vitro and in vivo is orchestrated by GCC through suppression of signaling by AKT, a key mediator of neoplastic transformation. Pharmacologic and genetic inhibition of AKT signaling mimics, while constitutive activation eliminates, the ability of GCC to regulate proliferative and metabolic programming in human colon cancer cells. GCC suppresses AKT signaling by inducing a cyclic GMP-dependent activation of the phosphatase and tensin homolog (PTEN), an antagonist of phosphoinositide 3 (PI3)-kinase signaling central to activating AKT. In the context of the universal loss of guanylin and uroguanylin early in neoplastic transformation, these observations reveal for the first time the molecular mechanisms coordinating reprogramming of replicative and metabolic circuits underlying tumor initiation in intestine. With hormone insufficiency initiating signal dysregulation reinforcing intestinal transformation, pervasive over-expression of GCC by human colorectal tumors offers a unique therapeutic opportunity for cancer prevention and regression through oral ligand replacement therapy.
Chemosensitivity testing to predict chemosensitivity for gemcitabine, using the biopsy specimens obtained by EUS-FNA from unresectable pancreatic cancer.
Authors: T. Wakatsuki, A. Irisawa, M. Terashima, T. Takagi, G. Shibukawa, H. Imamura, Y. Takahashi, A. Sato, M. Sato, H. Ohira, None Ohira
Journal: Journal of Clinical Oncology (2010)

e14640 Background: The purpose of this prospective study is to evaluate the feasibility of chemosensitivity testing using EUS-FNA samples and determine the optimal cut-off value of gemcitabine. Methods: Thirty-two consecutive patients, who were undergone EUS-FNA in our institute between October 2006 and July 2009, with unresectable pancreatic cancer were enrolled. All patients were treated with gemcitabine. Chemosensitivity (treated/control ratio: T/C) was calculated as the percentage of quantity of ATP of a tumor treated with gemcitabine and of control. Concentration of gemcitabine was 20 μg/mL according to the peak plasma concentration. To identify the cut-off value that could predict 180 days of PFS, receiver operating characteristic (ROC) curve and corresponding area under the curve (AUC) was calculated. Results: Thirty-three times assays were performed on 32 patients. Twenty-eight patients (87.5%) were successful. Four patients of 28 patients were excluded because of impossible to keep the protocol, therefore, 24 patients could be prospectively followed. After 2 cycles chemotherapy, tumor response were PR in 2, SD in 13, and PD in 9. Response (PR) rate was 8.3%, progression arrest (PR+SD) rate was 62.5%. Median PFS was 108 days, and Median OS was 264 days. The cut-off value was determined as 74% using the ROC analysis (area under the curve = 0.727; 95% CI = 0.457-0.997). From above results, we could predict 180 days PFS with a sensitivity and specificity of 71.4% and 88.2%, respectively. When patients were divided into two groups at T/C ratio 74%, there was a significant difference between 2 groups about PFS (median: 77 vs. 205 days, p = 0.0059), on the other hand, there was no significant difference about OS. With respect to tumor response, there was no significant difference in response rate, however, there was a significant difference in progression arrest (p = 0.015). In addition, T/C ratio < 74% was only significant prognostic factor that influence PFS. Conclusions: Chemosensitivity testing usig EUS-FNA sample is feasible. According to this definition, it might be possible to select the patients who are expected favorable result by gemcitabine treatment. No significant financial relationships to disclose.
Alterations in calcium metabolism in patients on long-term bisphosphonate therapy for metastatic breast cancer (MBC): A potential therapeutic target?
Authors: C. Simmons, G. Dranitsaris, M. Clemons, B. Y. Wong, R. Veith, D. E. Cole
Journal: Journal of Clinical Oncology (2007)

1044 Background: The effect of long-term potent BP use on calcium homeostasis in MBC pts is poorly understood. These effects and the need for calcium and Vitamin D supplementation may have significant implications for pt management in both the metastatic and adjuvant settings. Methods: We evaluated serum calcium (sCa), PTH, and 25(OH)D levels and their inter-relationships in 30 MBC pts after prolonged BP use for bone metastases (BM), compared with a control group (CG) of 1484 normal women without bone or mineral disease (JCEM 2003;88:185). The MBC pts were prescribed oral calcium (1g/d) and vitamin D (400IU/d) for 1 month prior to analysis. To determine whether MBC pts differed from CG with respect to the sCa-PTH correlation, logistic regression was performed with sCa, log-transformed PTH and an interaction term (Ca × lnPTH). Results: Mean age of the two groups did not differ [MBC group (58.5 ± 2.0 yr) vs. CG (55.2 ± 0.4 yr, p &gt;.05)]. VitD-deficiency (25vitD &lt; 40 nM) was equally prevalent in the two groups [MBC (23%) vs. CG (25%)]. sCa was significantly higher in MBC pts (2.473 ± 0.019 mM) compared to CG (2.377 ± 0.003, p &lt;0.001). However, PTH was not decreased in MBC pts (4.60 ± 0.36 pM), compared to CG (4.56 ± 0.06, t-test, p=0.91). Logistic regression was highly significant (p&lt;0.0001), as were coefficients for both explanatory variables (sCa, p &lt;0.0001 and lnPTH, p = 0.009) and their interaction (p=0.011). Conclusion: In pts with BM and prolonged BP use there appears to be a shift in the calcium set-point such that PTH release is activated by higher levels of sCa than in controls. We are currently studying whether prophylaxis for relative vit D deficiency in this population can not only correct this shift but also improve pt symptoms No significant financial relationships to disclose.
Cryoablation as an adjunctive therapy in a multimodality treatment program for malignant pleural mesothelioma.
Authors: R. B. Cameron, R. Farhadi, F. Abtin, R. Suh
Journal: Journal of Clinical Oncology (2010)

e17531 Background: Therapy for malignant pleural mesothelioma (MPM) fails to control local/regional disease in most patients and uncontrolled local disease remains a major cause of mortality. Effective novel therapies for multifocal local disease are desperately needed. We hypothesized that cryoablation may help fill this need since it can be used in the pleura/chest wall without the severe pain associated with RF and microwave ablation and without the need for general anesthesia. Methods: We retrospectively reviewed a prospective database and identified patients with localized MPM who had undergone cryoablation. Outpatient CT-guided procedures using single or multiple cryo-probes (up to 4) depending on lesion size were used to deliver two 10 minute cryoablation cycles with an 8 minute thaw period between. We analzyed patient characteristics, morbidity, and response rates. Results: 30 total lesions in 15 MPM patients were treated. 12 patients had prior surgery and were pathologically staged as stage I (2=16.7%), III (8=66.6%) and IV (2=16.7%). N2 disease was present in 6/12 (50%). Lesions in the surgical group were treated at a median of 564 days following surgery (range 201-2,774). Moribidy was limited to one case of skin erythema with a superficial chest wall lesion and one case of significant pain with a paraspinous lesion. Responses were seen in 20 (67%) lesions, stable disease in 5 (16.5%) and progression occurred in only 5 (16.5%). This compares favorably to results from our database with other tumors. Median survival of patients following surgery was 866 days (range 365-2,938) and following cryoablation was 160 days (range 75-444). 6 patients are still alive (50%) and 3 patients had no followup survival information available. Conclusions: Cryoablation can provide excellent palliation for local/regional recurrence following surgery or even primary disease in patients with malignant pleural mesothelioma and should be strongly considered in patients who have limited localized disease and no other viable treatment options. Successful employement of cryoablation potentially may lead to longer survivals in MPM due to improved local disease control. No significant financial relationships to disclose.