tbuckley/cabot-search huggingface dataset:
Validation of the lung cancer staging system revisions using a large prospective clinical trial database (ACOSOG Z0030).
Authors: J. J. Fibla, S. D. Cassivi, P. A. Decker, M. S. Allen, G. E. Darling, R. J. Landreneau, R. J. McKenna, D. R. Jones, R. I. Inculet, J. B. Putnam
Journal: Journal of Clinical Oncology (2010)

7021 Background: A new revision of the international lung cancer staging system has been recently introduced. The revisions are largely focused on the T descriptor. We sought to test the validity of this new system on a separate prospectively collected cohort of patients from a recent multicenter trial of early-stage lung cancer. Methods: We reviewed the prospectively collected data from 1,087 patients undergoing pulmonary resection for lung cancer in the ACOSOG Z0030 trial. TNM descriptors and overall staging were assessed using both the 6th and 7th editions of the AJCC/UICC lung cancer staging system. Survival results were analyzed according to both staging allocations. Results: The number of patients by stage in the 6th and 7th edition allocations respectively were as follows: IA (454, 453); IB (417, 314); IIA (42, 180); IIB (107, 75); IIIA (44, 64); IIIB (23,1); there were no stage IV patients by either version. Overall survival comparisons are provided in the Table. Conclusions: This study provides the first external validation of the recently revised lung cancer staging system using a large multicenter database. Inasmuch as its revisions concentrate predominantly on the T descriptor, the 7th edition does produce prognostic results that demonstrate monotonic progression, distinction between groups, and homogeneity within groups. The 7th edition of the AJCC/UICC lung cancer staging system appears to be an improvement over the preceding system. 6th edition T/N stage Median survival (yrs) 5-year survival (%) p value* T1 NA 73.5 - T2 6.9 59.1 <0.0001 T3 2.6 24.3 0.0002 T4 2.4 44.4 0.5232 N0 8.7 68.2 - N1 4.0 43.3 <0.0001 N2 2.7 36.1 0.6881 IA NA 76.0 - IB 7.9 62.9 <0.0001 IIA 3.9 46.1 0.0181 IIB 3.9 41.2 0.7026 IIIA 1.8 28.0 0.2678 IIIB 2.4 44.4 0.4806 7th edition T/N stage T1 NA 74.4 - T1a NA 75.4 - T1b 9.1 73.1 0.3896 T2 6.9 59.2 - T2a 6.9 61.2 0.0058 T2b 5.1 51.1 0.0631 T3 3.0 39.6 0.2088 T4 1.4 - 0.0041 N0 8.7 68.2 - N1 4.0 43.3 <0.0001 N2 2.7 36.1 0.6881 IA NA 77.0 - IB 8.5 64.9 0.0002 IIA 4.4 48.5 0.0003 IIB 3.6 42.9 0.4668 IIIA 1.8 30.6 0.1203 T1 vs. T2, p value < 0.0001 T2 vs. T3, p value = 0.0021 T3 vs. T4, p value = 0.0041. * Stage groups were consecutively compared (i.e., IA vs. IB, IB vs. IIA, etc.). No significant financial relationships to disclose.
Five-year follow-up of preoperative chemotherapy (Cx) of docetaxel with or without cisplatin for clinical (c-) stage IB/II non-small cell lung cancer (NSCLC): Report of a Japan Clinical Oncology Group study (JCOG0204).
Authors: H. Kunitoh, M. Tsuboi, H. Asamura, H. Tada, K. Nagai, T. Mitsudomi, T. Koike, T. Shibata, N. Saijo
Journal: Journal of Clinical Oncology (2010)

7059 Background: We conducted a randomized phase II trial in order to evaluate the safety and efficacy of the preoperative docetaxel (D) with or without cisplatin (P) in c-stage IB/II, resectable NSCLC, and reported preoperative DP combination resulted in favorable short-term relapse-free survival (RFS) rate (Br J Cancer 2008). Five-year follow-up data are presented herein. Methods: Patients (pts) with pathologically documented c-stage IB/II NSCLC, performance status (PS) 0-1 and ample organ functions were eligible. Pts were randomized to receive either two cycles of DP given q4 (q3 allowed) weeks: P 80mg/m2 and D 60mg/m2 on day 1, or, three cycles of D 70mg/m2 q3weeks. Pts went on to thoracotomy after completion of the Cx. Preoperative Cx could be stopped and switched to surgery when tumor size increased >10% in diameter. Results: From October 2002 to November 2003, 80 pts were randomized. Median age 65 (range 30-74), M/F 62/18, c-IB/II 45/35, PS 0/1 66/14, histology Ad/Sq/Others 54/21/5 (including 1 ineligible sarcoma). As of December 2008 monitoring, all 79 eligible pts (40 in DP and 39 in D) were followed-up for 5 years. The RFS rates and overall survival (OS) rates according to the clinical stage are summarized in the Table. The hazard ratio of RFS in the DP to the D arm was 0.57 (95% confidence interval: 0.31-1.04), and that of OS was 0.48 (95% confidence interval: 0.27-0.98). Conclusions: The preoperative DP combination, which had shown favorable short-term RFS rate, was also promising in terms of OS data. Short-term RFS seems to be a good surrogate of mature OS. Treatment arm DP D Clinical stage All IB II All IB II Number of pts 40 22 18 39 22 17 RFS at 1 yr (%) 78 (61-88)* 91 61 62 (45-75)* 64 59 RFS at 3 yrs (%) 65 (48-78)* 73 56 39 (24-53)* 46 29 RFS at 5 yrs (%) 58 (41-71)* 64 50 36 (21-51)* 41 29 OS at 1 yr (%) 88 (73-95)* 96 78 90 (75-96)* 86 94 OS at 3 yrs (%) 80 (64-90)* 96 61 62 (45-75)* 68 53 OS at 5 yrs (%) 75 (59-86)* 91 56 46 (30-61)* 50 41 * 95% confidence interval. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis
Part 3: Defibrillation
Journal: Circulation (2005)

The 2005 Consensus Conference considered questions related to the sequence of shock delivery and the use and effectiveness of various waveforms and energies. These questions have been grouped into the following categories: (1) strategies before defibrillation, (2) use of automated external defibrillators (AEDs), (3) electrode-patient interface, (4) use of the electrocardiographic (ECG) waveform to alter management, (5) waveform and energy levels for the initial shock, (6) sequence after failure of the initial shock (ie, second and subsequent shocks), and (7) other related topics.

The ECC Guidelines 2000 1 state that defibrillation should be attempted as soon as ventricular fibrillation (VF) is detected, regardless of the response interval (ie, time between collapse and arrival of the AED). If the response interval is >4 to 5 minutes, however, there is evidence that 1½ to 3 minutes of CPR before attempted defibrillation may improve the victim’s chance of survival. The data in support of out-of-hospital AED programs continues to accumulate, and there is some evidence supporting the use of AEDs in the hospital. Analysis of the VF waveform enables prediction of the likelihood of defibrillation success; with this information the rescuer can be instructed to give CPR or attempt defibrillation. This technology was developed by analysis of downloads from AEDs; it has yet to be applied prospectively to improve defibrillation success and is not available outside research programs.

All new defibrillators deliver a shock with a biphasic waveform. There are several varieties of biphasic waveform, but the best variant and the optimal energy level and shock strategy (fixed versus escalating) have yet to be determined. Biphasic devices achieve higher first-shock success rates than monophasic defibrillators. This fact, combined with the knowledge that interruptions to chest compressions are harmful, suggests that a 1-shock strategy (1 shock followed immediately by CPR) may be preferable to …
Activation of STING-Dependent Innate Immune Signaling By S-Phase-Specific DNA Damage in Breast Cancer
Authors: Eileen E. Parkes, Steven M. Walker, Laura E. Taggart, Nuala McCabe, Laura A. Knight, Richard Wilkinson, Karen D. McCloskey, Niamh E. Buckley, Kienan I. Savage, Manuel Salto-Tellez, Stephen McQuaid, Mary T. Harte, Paul B. Mullan, D. Paul Harkin, Richard D. Kennedy
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Previously we identified a DNA damage response–deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling. In this study, we address the mechanism of this immune response and its possible clinical significance. Methods: We used immunohistochemistry (IHC) to characterize immune infiltration in 184 breast cancer samples, of which 65 were within the DDRD subtype. Isogenic cell lines, which represent DDRD-positive and -negative, were used to study the effects of chemokine release on peripheral blood mononuclear cell (PBMC) migration and the mechanism of immune signaling activation. Finally, we studied the association between the DDRD subtype and expression of the immune-checkpoint protein PD-L1 as detected by IHC. All statistical tests were two-sided. Results: We found that DDRD breast tumors were associated with CD4+ and CD8+ lymphocytic infiltration (Fisher's exact test P < .001) and that DDRD cells expressed the chemokines CXCL10 and CCL5 3.5- to 11.9-fold more than DNA damage response–proficient cells (P < .01). Conditioned medium from DDRD cells statistically significantly attracted PBMCs when compared with medium from DNA damage response–proficient cells (P < .05), and this was dependent on CXCL10 and CCL5. DDRD cells demonstrated increased cytosolic DNA and constitutive activation of the viral response cGAS/STING/TBK1/IRF3 pathway. Importantly, this pathway was activated in a cell cycle–specific manner. Finally, we demonstrated that S-phase DNA damage activated expression of PD-L1 in a STING-dependent manner. Conclusions: We propose a novel mechanism of immune infiltration in DDRD tumors, independent of neoantigen production. Activation of this pathway and associated PD-L1 expression may explain the paradoxical lack of T-cell-mediated cytotoxicity observed in DDRD tumors. We provide a rationale for exploration of DDRD in the stratification of patients for immune checkpoint–based therapies.
Infectious disease associations in indolent lymphoma (follicular, FL and non-follicular, nFL): Developing a lymphoma prevention strategy
Authors: C. S. Portlock, A. Noy, P. Hamlin, J. Qin, L. Rosenzweig, S. Corcoran, W. Chey, G. Papanicolaou, A. Markowitz
Journal: Journal of Clinical Oncology (2004)

6701 Background: The antigen-drive association of gastric MALT lymphoma with H. pylori is well recognized. Successful antibiotic therapy can result in lymphoma remission, and with it, lymphoma prevention. We have sought to prospectively identify possible associated infections (candidates for antigen-drive) in patients with non-bulky, advanced stage indolent lymphoma as the first step to such a lymphoma treatment/ prevention strategy. These patients are often given a recommendation of monitoring (“watch and wait”) and it is during this period that a window of opportunity may exist to identify and treat antigen-drive related infections. Methods: Patients with a new diagnosis of indolent lymphoma (FL and nFL), stages II (intra-abdominal), III and IV fulfilling GELF criteria for observation were eligible. Studies performed: Stool H. pylori, Hepatitis C and Borrelia serologies, Borrelia and Chlamydia fixed tissue PCR, peripheral blood mononuclear cell PCR for Chlamydia, and a hydrogen breath test for small bowel bacterial overgrowth. Results: To date 13 patients have been enrolled with IRB informed consent: 9 females, 4 males; median age, 51 years (34–70); 7 FL, 6 nFL; stage II (1 pt), III (3), and IV (9). All met GELF criteria for observation. Infections tested thus far include: H. pylori (3 positive, nFL); Hepatitis C (2+; 1FL, 1nFL); and small bowel bacterial overgrowth (3+; 1FL, 2nFL). Borrelia serologies were negative in all 13 pts. PCR for Borrelia and Chlamydia are pending. Thus, 7 of 13 patients have at least one positive study. These infections have been/are being treated and clinical outcomes of lymphoma will be assessed. Conclusions: Infections are common in advanced stage indolent lymphoma (54% to date in our series). The identification of antigen-drive associated infections may be a first step toward developing a lymphoma prevention strategy. No significant financial relationships to disclose.
A Significant Early Detection Of Poor Outcome In Acute Myeloid Leukemia Patients Having a Minimal Residual Disease Using Multiparameter Flow Cytomerty Combined To Mixed Chimerism At Three Months After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Florence Beckerich, Mohamad Sobh, Stephane Morisset, Adriana Plesa, Valerie Dubois, Isabelle Mollet, Helene Labussiere, Lila Gilis, Sophie Ducastelle, Oriane Le Borgne, Jeremy Monfray, Fiorenza Barraco, Isabelle Tigaud, Xavier Thomas, Franck E. Nicolini, Mauricette Michallet
Journal: Blood (2013)
Kaurenoic acid antitumor activity in breast cancer cells.
Authors: F. M. Peria, D. G. Tiezzi, D. P. Tirapelli, F. S. Neto, C. R. Tirapelli, S. Ambrosio, H. F. Oliveira, L. Tirapelli
Journal: Journal of Clinical Oncology (2010)

e13641 Background: A new class of molecules, the kaurane-type dipertene, extracted from a native American plant, were described with antimicrobial and antiparasitic activities and demonstrated either a cytotoxic antiproliferative action in tumor cells cultures as colon cancer and leukemia, with dose-dependent effects in non cancer cells. One of this kaurane-type dipertene, ent-kaur-16-en-19-oic acid (kaurenoic acid, KA), has particular interest as a new cycle unspecific cytotoxic drug against hematological and non hematological cancer cells.This study evaluated the cellular responses to treatment with KA on human breast cancer cell lines MCF7, SKBR3 and normal human breast cell HB4A. Such responses were analyzed in terms of cell survival. Methods: Cell viability assay was assessed by trypan blue dye-exclusion method in MCF7, SKBR3 and HB4A cells untreated and treated with KA (30, 50 and 70 μM) for 24, 48 and 72h. Results: Treatments of MCF7 and SKBR3 cells with KA clearly reduced the cell viability. Interesting the HB4A cell line was resistant to treatment with KA, which demonstrated a selectivity activity of KA for the cancerous cells. The cell line MCF7 (proficient P53) showed approximately 40% of death, while the SKBR3 cell line (mutated p53) obtained 25% of death with 70 μM. Conclusions: Kaurenoic acid reduced cell viability with selectivity and antitumor activity in breast cancer cells. These results demonstrated that the P53 protein has an important role in the mechanism of action of KA. KA may serve as leading compound for the development of the new chemotherapeutic drugs for breast cancer. No significant financial relationships to disclose.
Serum Levels of CCL22 and CCL25 Might Predict Skin Rash Induction、the Common Adverse Event By Bendamustine Therapy in Malignant Lymphoma
Authors: Yasuhito Terui, Kyoko Ueda, Yoshiharu Kusano, Tadahiro Gunji, Noriko Nishimura, Kiyohiko Hatake
Journal: Blood (2014)
High expression level of insulin-like growth factor I receptor is associated with regional lymph node metastasis
Authors: Y. Jiang, L. Wang, W. Gong, J. A. Ajani, J. L. Abbruzzese, K. Xie
Journal: Journal of Clinical Oncology (2004)

4115 Background: Over-expression of the insulin-like growth factor I receptor (IGF-IR) has been found in many types of human cancers. In vivo, inhibition of the function of IGF-IR results in apoptosis and tumor growth attenuation, indicating that altered expression of IGF-IR may play an important role in human cancer. However, the role of IGF-IR in gastric cancer has not been explored. Methods: In this study, we determined the expression status of the IGF-IR in primary gastric cancer using immunohistochemistry. Results: In the 86 cases of resected gastric cancer examined, IGF-IR was over-expressed in 61.6% gastric tumor samples as compared to the adjacent cancer-free gastric mucosa (p=0.018). In patients with lymph node metastasis, high expression level of IGF-IR was detected in both the primary tumor site and metastatic tumor cells with lymph nodes (p=0.0102), implicating IGF-IR in the development of lymph node metastasis. It has been reported that the transcription factor Sp1 transactivates the IGF-IR promoter and regulates IGF-IR expression. We have previously showed that over-expression of Sp1 in gastric cancer associated with advanced stage and predicted poor survival. In the current study, the expression level of IGF-IR correlated with that of Sp1 (p=0.018). Further, the median survival for patients with low and high IGF-IR expression was 1242 days and 792 days, respectively. However, this survival difference was not statistically significant (p=0.16), indicating that a larger scale study is warranted to further determine the value of IGF-IR as a prognostic/survival marker. Conclusions: Taken together, our data suggest that alteration of IGF-IR expression is likely to play a significant role in the development and metastasis of gastric cancers. Although it is not an independent survival predictor, it is one of the essential down steam components of Sp1 that might affect patient outcome. No significant financial relationships to disclose.
Risk of poor development in young children in low-income and middle-income countries: an estimation and analysis at the global, regional, and country level
Authors: Chunling Lu, Maureen M Black, Linda M Richter
Journal: The Lancet Global Health (2016)

BackgroundA 2007 study published in The Lancet estimated that approximately 219 million children aged younger than 5 years were exposed to stunting or extreme poverty in 2004. We updated the 2004 estimates with the use of improved data and methods and generated estimates for 2010.MethodsWe used country-level prevalence of stunting in children younger than 5 years based on the 2006 Growth Standards proposed by WHO and poverty ratios from the World Bank to estimate children who were either stunted or lived in extreme poverty for 141 low-income and middle-income countries in 2004 and 2010. To avoid counting the same children twice, we excluded children jointly exposed to stunting and extreme poverty from children living in extreme poverty. To examine the robustness of estimates, we also used moderate poverty measures.FindingsThe 2007 study underestimated children at risk of poor development. The estimated number of children exposed to the two risk factors in low-income and middle-income countries decreased from 279·1 million (95% CI 250·4 million–307·4 million) in 2004 to 249·4 million (209·3 million–292·6 million) in 2010; prevalence of children at risk fell from 51% (95% CI 46–56) to 43% (36–51). The decline occurred in all income groups and regions with south Asia experiencing the largest drop. Sub-Saharan Africa had the highest prevalence in both years. These findings were robust to variations in poverty measures.InterpretationProgress has been made in reducing the number of children exposed to stunting or poverty between 2004 and 2010, but this is still not enough. Scaling up of effective interventions targeting the most vulnerable children is urgently needed.FundingNational Institutes of Health, Bill & Melinda Gates Foundation, Hilton Foundation, and WHO.
Survey of Clostridium difficile infection surveillance systems in Europe, 2011
Authors: Axel Kola, Camilla Wiuff, Thomas Akerlund, Birgit H van Benthem, Bruno Coignard, Outi Lyytikäinen, Doris Weitzel-Kage, Carl Suetens, Mark H Wilcox, Ed J Kuijper, Petra Gastmeier
Journal: Eurosurveillance (2016)

To develop a European surveillance protocol for Clostridium difficile infection (CDI), existing national CDI surveillance systems were assessed in 2011. A web-based electronic form was provided for all national coordinators of the European CDI Surveillance Network (ECDIS-Net). Of 35 national coordinators approached, 33 from 31 European countries replied. Surveillance of CDI was in place in 14 of the 31 countries, comprising 18 different nationwide systems. Three of 14 countries with CDI surveillance used public health notification of cases as the route of reporting, and in another three, reporting was limited to public health notification of cases of severe CDI. The CDI definitions published by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Centre for Disease Prevention and Control (ECDC) were widely used, but there were differing definitions to distinguish between community- and healthcare-associated cases. All CDI surveillance systems except one reported annual national CDI rates (calculated as number of cases per patient-days). Only four surveillance systems regularly integrated microbiological data (typing and susceptibility testing results). Surveillance methods varied considerably between countries, which emphasises the need for a harmonised European protocol to allow consistent monitoring of the CDI epidemiology at European level. The results of this survey were used to develop a harmonised EU-wide hospital-based CDI surveillance protocol.
A 7-Year-Old Girl With Periorbital Edema, Ecchymosis, and Conjunctival Hemorrhage
Authors: Elizabeth M. Keating, Debra L. Palazzi
Journal: JAMA Pediatrics (2016)

A previously healthy 7-year-old girl presented with fever, sore throat, bilateral conjunctival hemorrhage, periorbital edema, and eyelid ecchymoses. The illness began 1 week prior with low-grade fever and back pain. What is your diagnosis?
Phenotypic, Transcriptomic and Genomic Characterization Of Clonal Plasma Cells (PCs) From Newly Diagnosed Patients With Light Chain Amyloidosis (AL)
Authors: Bruno Paiva, Luis A Corchete, Norma Gutierrez, María-Belén Vidriales, Irene Aires-Mejia, Maria Luz Sanchez, Paloma Barcena, Ramon Garcia-Sanz, Enrique M. Ocio, Rebeca Cuello, Alfonso Garcia de Coca, Emilia Pardal, Fernando Escalante, Tomas J Gonzalez-Lopez, Jose M Alonso, Magdalena Sierra, Maria-Carmen Montes, Abelardo Bárez, Jose Hernandez, Josefina Galende, Alberto Orfao, Maria-Victoria Mateos, Jesus F San Miguel
Journal: Blood (2013)
European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): a real-life clinical assessment
Authors: M. A. Calderón, C. Vidal, P. Rodríguez del Río, J. Just, O. Pfaar, A. I. Tabar, I. Sánchez-Machín, P. Bubel, J. Borja, P. Eberle, R. Reiber, M. Bouvier, A. Lepelliez, L. Klimek, P. Demoly
Journal: Allergy (2016)

Outside clinical trials, data on systemic reactions (SRs) due to allergen immunotherapy (AIT) are scarce.A prospective, longitudinal, web-based survey of 'real-life' respiratory allergen immunotherapy (AIT) clinical practice was conducted in France, Germany and Spain. SRs were recorded and coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and risk factors associated with SRs were identified.A total of 4316 patients (corresponding to 4363 ongoing courses of AIT) were included. A total of 109 SRs were recorded, and 90 patients (2.1%) presented at least one SR. Most of the SRs occurred in subcutaneous allergen immunotherapy (SCIT) (89%, n = 97). The most frequently reported symptoms were urticaria, rhinitis, dyspnoea and cough. Respiratory symptoms appeared before skin symptoms. Most SRs occurred during the up-dosing phase (75.8%) and were mild in severity (71.6%). Intramuscular adrenaline was administered in 17 SRs, but only 65% of these were subsequently classified as anaphylaxis. Independent risk factors for SRs during SCIT were as follows: the use of natural extracts (odds ratio, OR) [95% confidence interval (CI)] = 2.74 [1.61-4.87], P = 0.001), the absence of symptomatic allergy medications (1.707 [1.008-2.892], P = 0.047), asthma diagnosis (1.74 [1.05-2.88], P = 0.03), sensitization to animal dander (1.93 [1.21-3.09], P = 0.006) or pollen (1.16 [1.03-1.30], P = 0.012) and cluster regimens (vs rush) (4.18 [1.21-14.37], P = 0.023). A previous episode of anaphylaxis increased the risk for anaphylaxis in SCIT (OR [95% CI] = 17.35 [1.91-157.28], P = 0.01).AIT for respiratory allergy is safe, with a low number of SRs observed in real-life clinical practice. A personalized analysis of risk factors could be used to minimize SRs.