tbuckley/cabot-search huggingface dataset:
ABVD vs. STANFORD V (SV) vs. MOPP-EBV-CAD (MEC) in advanced Hodgkin's lymphoma. Final results of the IIL HD9601 randomized trial
Authors: M. Federico, A. Levis, S. Luminari, T. Chisesi, L. Marcheselli, M. Goldaniga, U. Vitolo, S. Neri, M. Brugiatelli, P. G. Gobbi
Journal: Journal of Clinical Oncology (2004)

6507 Background: About 30% of patients with advanced Hodgkin's lymphoma (HL) do not respond to initial therapy with ABVD or relapse. Recently SV and MEC were reported with higher cure rates. To test the superiority of SV and MEC over ABVD the Intergruppo Italiano Linfomi (IIL) conducted a three arms multicentric randomized trial. Methods: Patients with advanced stage HL (IIB-IV) and no previous treatment were randomised to receive 6 courses of ABVD or 6 courses of MEC or 12 weeks of SV. At the end of chemotherapy radiotherapy was delivered to residual masses or to the sites of previous bulky disease. The principal end point of the study was failure free survival (FFS): complete response (CR) rate, Freedom From Progression (FFP) and Overall Survival (OS) were secondary end-points of the study. Results: From January 1996 to April 2000, 355 pts were randomized; 23 cases were excluded due to missing data (22) or to revised histology (1). Finally 332 (94%) patients were assessed for response and survival. Baseline characteristics were well balanced among the three groups. Radiotherapy was delivered to 64%, 45% and 66% of patients treated with ABVD, MEC or SV, respectively. At the end of the therapy a CR was achieved by 88% of pts treated with ABVD, 94% with MEC and 72% with SV (P < 0.01). After a median follow-up of 56 months (60 months for alive pts), the 5-year FFS was 83%, 85% and 67% for ABVD, MEC and SV respectively (p<0.01); 5-year OS was 90%, 90% and 83% (p=ns) for ABVD, MEC and SV respectively. In addition 5-yrs FFP was 86% for ABVD, 93% for MEC and 76% for SV (p<0.01). Hematological toxicity was higher for MEC than for the other two regimens; grade III-IV leukopenia: 13% vs. 51% vs. 30% (p<0.01). Grade III-IV infections: 1% vs. 14% vs. 0% (p<0.01). Other extra-hematological toxicities were comparable in the three arms. At the time of present analysis, 2 pts per each arm died due to second cancer. Conclusions: The results of the HD9601 trial show an advantage of ABVD and MEC over SV in terms of response, FFS and FFP. No significant financial relationships to disclose.
The AJCC staging system does not predict survival in patients receiving multimodality therapy for esophageal cancer
Authors: N. P. Rizk, M. S. Bains, D. H. Ilson, B. Minsky, V. W. Rusch
Journal: Journal of Clinical Oncology (2005)

4005 Background: AJCC stage is an accepted means of stratifying esophageal cancer patients prognostically after surgical resection but may not be accurate in patients receiving multimodality therapy. The purpose of this study was to establish prognostic pathologic variables following pre-operative chemotherapy and radiation. Methods: Retrospective review of all patients with esophageal adenocarcinoma and squamous cell carcinoma (SCC) who received radiation concurrently with chemotherapy (CRT), and subsequently underwent esophagectomy. Data collected included demographic information, pathologic findings, and overall survival. Statistical methods included recursive partitioning (RP) and Kaplan-Meier (KM) analyses. Results: From 1/96 to 9/03, 674 patients underwent an esophagectomy, of which 284 patients were appropriate for this analysis. KM analysis indicates that the current AJCC system poorly distinguishes between stages 0-IIb (n=212, p=0.90) and III-IVb (n=72, p=0.55). RP analyses using T, N, and M as prognostic variables and stratified by histology indicates that in adenocarcinoma, the presence of involved lymph nodes and metastatic disease but not depth of invasion predict survival. In SCC, patients with a pathologic complete response (pCR) had the best survival, followed by patients with T1–3N0 and T1–3N1 disease. Conclusions: The current AJCC staging system and the emphasis on pCR following CRT inaccurately stratifies patients after multimodality therapy. In adenocarcinoma, a 3-tiered staging system (N0, N1, M1) is most appropriate, whereas in SCC a 4-tiered staging system (pCR, N0, N1, M1) most accurately predicts survival. No significant financial relationships to disclose.
Abstract 287: Tcf7l2 Expression By Insulin And High Glucose
Authors: Ning Hou, Bo Ye, Lu Xiao, Haodong Xu, Faqian Li
Journal: Circulation Research (2013)

Backgrounds: Genetic variations of TCF7L2, a nuclear transcriptional factor in canonical Wnt signaling are associated with increased risks of Diabetes Mellitus. How TCF7L2 is regulated by diabetic conditions in the heart is poorly understood. Methods: TCF7L2 expression was investigated by Western blotting in HL-1 cells treated with 14 mM mannitol (M), 25 mM glucose (G), 10 nM insulin (I), and G plus I (G+I). In addition, TCF7L2 levels were examined by Western blotting in the heart of B6.Cg-m Leprdb/+ +/J (db) and C57Bl/6J (C57) mice 4 hours after intraperitoneal injections of 1.5 IU/kg insulin. Result: The expression of TCF7L2 was higher in db than C57 hearts. Insulin treatment decreased TCF7L2 in C57 hearts. Paradoxically, TCF7L2 was further increased by insulin in db hearts. In HL-l cells, TCF7L2 started to decrease at one hour and remained lower up to 24 hours after insulin treatment compared to untreated controls. In contrast, G increased TCF7L2 expression at 1, 6 and 24 hours after treatment relative to M. Insulin could decrease TCF7L2 at 1 and 6 hours, but failed to do so at 24 hours in G+I. At 48 hours, no difference in TCF7L2 expression was observed among different treatment groups. Conclusion: Insulin regulation of TCF7L2 is interfered by high glucose in vitro and misregulation of TCF7L2 in the heart of diabetic mice may contribute to the pathogenesis of diabetic cardiomyopathy.
Bone markers in prostate cancer (PC) patients: Biologic criteria to identify patients at risk of developing distant metastases
Authors: J. Ayllon, E. Banu, F. Leviel, P. Houillier, J. Medioni, E. Barrascout, S. Oudard, G. Maruani
Journal: Journal of Clinical Oncology (2009)

e16069 Background: Currently, there are no specific serum and/or urinary bone markers able to accurately identify PC patients with hormone-refractory disease and/or those with distant metastases. Methods: Four categories of PC patients were defined as follows: A. hormone-sensitive without distant metastases; B. hormone-sensitive with metastases; C. hormone-refractory without metastases; D. hormone-refractory with metastases. The serum bone markers investigated were osteogenesis-related [Osteocalcin (OC), procollagen type 1 amino-terminal propeptide (P1NP), bone alkaline phosphatase (BALP)], osteolysis-related [beta collagen 1 carboxyterminal peptide (βCTX), carboxyterminal telopeptide type 1 collagen (1CTP), tartrate resistant acid phosphatase (TRAP)] or osteoclastogenesis-related [osteoprotegerin (OPG)]. Receiver Operating Characteristic (ROC) curves and the Area Under these curves were used to estimate the overall accuracy of each marker in discriminating between the four categories (A vs. BCD; B vs. ACD; C vs. ABD and D vs. ABC) with no adjustment for multiplicity. Parametric (Student's t-test) and non-parametric (Kruskal- Wallis) tests were conducted too. All statistical analyses were performed by means of SPSS v 16 (SPSS Inc). Results: Data were from 40 consecutive PC patients treated at the Georges Pompidou European Hospital in Paris, France and who were equally distributed between categories. Hormone-refractory patients with distant metastases were accurately identified by P1NP, 1CTP and TRAP. The respective areas under the ROC values were 0.76, 0.84 and 0.79 (all Pvalues less than 0.01). None of the markers identified category B of patients. Conclusions: Some bone-related serum markers may be associated with the onset of hormone-refractory status and distant metastases. They should be prospectively validated in a larger cohort of patients. No significant financial relationships to disclose.
Controversies in Management: Eradication largely prevents relapse
Authors: C J Hawkey
Journal: BMJ (1994)

Nations Development Programme is planning to introduce regional offices and Unicef is strengthening its own regional structure.On a practical level, staff say that having regional offices reduces the time and money spent travelling to and from Geneva.Recently the independence of the offices has had the added benefit of insulating regional staff from the growing discontent in Geneva.WHO claims that the decentralisation allows fast, flexible, and relevant responses to the health needs ofmember states.But the regions give only the illusion of decentralisation, while duplicating activities in headquarters and delaying resources and information getting to the point of need.WHO will be fully effective only if the regions are made properly accountable, both politically and financially, and if more of their responsibility is devolved to country level.In the next article I will examine the role of the country offices and look at whether they are equipped to take on such additional responsibility.1 Danida.Effectiveness of multilateral agencies at country level: WHO in Kenya, Nepal, Sudan and Thailand.Copenhagen:
Abstract 291: Intestinal Microcirculatory Alterations in a Rat Model of Cardiac Arrest and Resuscitation
Authors: Jie Qian, Jiefeng Xu, Zhengfei Yang, Xianwen Hu, Jena Cahoon, Shijie Sun, Wanchun Tang
Journal: Circulation (2013)

Introduction: Abnormalities in intestinal microvascular blood flow are of increasing interest during the post-resuscitation phase following cardiac arrest because of the critical role attributed to the intestine in the pathogenesis of systemic inflammatory response, which potentially further aggravate post-resuscitation myocardial and cerebral dysfunction. The present study investigated post-resuscitation mesenteric microcirculatory dysfunctions in a rat model of cardiac arrest and resuscitation. Methods: Eight Sprague-Dawley rats were divided into two groups: 1) VF8+PC8 group: 8 mins of untreated VF followed by 8 mins of CPR and defibrillation (n=5); 2) sham control: animals only underwent surgical procedure (n=3). A laparotomy was performed to expose a segment of the jejunum. Twenty-second clips of the mesenteric microcirculation were captured with the sidestream dark field (SDF) video microscope at three locations at baseline and at 1, 2, 4, 6, 8 hours after the return of spontaneous circulation (ROSC). Mesenteric microcirculatory blood flow was quantified off-line by determining the microcirculatory flow index (MFI). Results: MFIs were significantly reduced 1 hour after ROSC and gradually recovered until it reached a peak at the 6th hour. This was followed by a remarkable decrease at the 8th hour. Compared with control group, MFIs reductions in the VF8+PC8 group were statistically significant (p&lt;0.01) at all time points except for 6 hours after ROSC. Conclusion: There was a significant reduction in mesenteric microcirculatory blood flow following successful resuscitation from cardiac arrest.
Response to Letter Regarding Article, “Trauma Exposure and Posttraumatic Stress Disorder Symptoms Predict Onset of Cardiovascular Events in Women”
Authors: Jennifer A. Sumner, Laura D. Kubzansky, Mitchell S.V. Elkind, Andrea L. Roberts, Jessica Agnew-Blais, Qixuan Chen, Magdalena Cerdá, Kathryn M. Rexrode, Janet W. Rich-Edwards, Donna Spiegelman, Shakira F. Suglia, Eric B. Rimm, Karestan C. Koenen
Journal: Circulation (2016)
Updated result on the 2.5-year follow-up of GC0301/TOP-002: Randomized phase III study of irinotecan plus S-1 (IRI-S) versus S-1 alone as first-line treatment for advanced gastric cancer (AGC)
Authors: A. Tsuburaya, H. Narahara, H. Imamura, K. Hatake, H. Imamoto, T. Esaki, M. Kato, H. Furukawa, C. Hamada, Y. Sakata
Journal: Journal of Clinical Oncology (2009)

4544 Background: IRI-S had longer in median survival time (MST) than S-1 alone, and was well tolerated in previously untreated AGC, but not statistically significant. Considering 68 patients (pts) were censored, further follow-up was needed to confirm the OS with more precision (Imamura et al. ASCO-GI 2008). We now present updated results of OS and exploratory analysis with the prolonged 2.5 year follow-up data. Methods: Treatments Arm A (oral S-1 80 mg/m 2 /day from Day 1 to 28, q6w), or Arm B (IRI-S; oral S-1 80 mg/m 2 /day from Day 1 to 21 and intravenous irinotecan 80 mg/m 2 on Days 1 and 15, q5w) were continued until disease progression or unacceptable toxicities were observed. The primary endpoint was to compare OS between groups. This updated result was regarded as exploratory position. Results: Although the MST of Arm A was 319 days (95%Cl: 286–395) and of Arm B was 389 days (95%Cl: 324–459), Arm B didn’t show statistically significant superiority to Arm A (log-rank test p=0.54; hazard ratio (HR) =0.93). The 1-year survival was 45.0% in Arm A and 52.0% in Arm B, and the 2-year survival was 22.5% and 18.0%, respectively. Response rate was significantly different (Arm A/B, 26.9%/41.5%; chi-square test p=0.04) in 187 patient evaluated by RECIST criteria. Time to treatment failure was also favored in Arm B (median=138 days) compared to Arm A (111 days; log-rank test p=0.16; HR=0.85). In subset analyses, two groups showed possibility of clinical benefit in Arm B. The HR of diffuse type group was 0.71 (95%Cl: 0.52–0.96), and of PS1, 2 group was 0.63 (95%Cl: 0.42–0.95). As post protocol treatment, 45.6% of Arm A patients received an irinotecan-based regimen, and the MST of them was 496 days (95%Cl: 395–573). Conclusions: IRI-S did not show statistically significant superiority to S-1 alone in OS with this follow-up data. Post protocol treatment, effective treatment after S-1 failure might have affected survival. According to exploratory analyses, IRI-S may have clinical benefit in early-term of treatment, group of the diffuse type and that of PS1, 2. We need more considering predictive factors, because the gastric cancer is heterogeneous adenocarcinoma. [Table: see text]
Abstract 266: The Impact of Chest Compression Release Velocity on Outcomes From Out-of-Hospital Cardiac Arrest
Authors: Sheldon Cheskes, Adam Byers, cathy zhan, Annemarie Silver, Laurie Morrison
Journal: Circulation (2013)

BACKGROUND: Previous studies have demonstrated significant relationships between CPR quality metrics and survival to hospital discharge from out-of hospital (OHCA) cardiac arrest. Recently a new metric, chest compression release velocity (CCRV) has been associated with improved survival from OHCA. OBJECTIVE: To determine the impact of CCRV on clinical outcomes from OHCA. METHODS: We performed a retrospective review of prospectively collected data on all treated adult OHCA occurring over a one year period (Jan 2012 - Jan 2013) in two Canadian EMS agencies. CPR metrics of chest compression fraction (CCF), compression rate, compression depth, shock pause duration and CCRV were abstracted from impedance channel measurements during each resuscitation. Cases of public access defibrillation, EMS witnessed arrest and those missing any Utstein variable or discharge status data were excluded. We performed a multivariable regression analysis to determine the impact of CCRV on survival to hospital discharge. Secondary outcome measures were the impact of CCRV on return of spontaneous circulation (ROSC) and neurologically intact survival (MRS ≤ 3). RESULTS: Among 908 treated OHCA, 611met inclusion criteria. The median (IQR) age was 71.7 (60.7, 81.6) with 395 (64.6%) being male. 140 (22.9%) presented in ventricular fibrillation, 122 (20%) pulseless electrical activity and 349 (57.1%) asystole. The median (IQR) CPR quality metrics were: CCF 0.81 (0.73, 0.85), compression rate 105/minute (101, 115), compression depth 49.9 mm (42.5, 56.7), pre-shock pause 13.5 secs (8, 19) and post-shock pause 3.5 secs (2.8, 5). The median (IQR) CCRV (mm/sec) amongst 49 survivors was 135.9 (115.4, 156.5) compared to 120 (102.9, 140) in 562 non survivors (p=0.009). When adjusted for CPR metrics and Utstein variables, the odds of survival to hospital discharge for each 5 mm/sec increase in CCRV was 1.02 (95% CI: 0.97, 1.08). Similarly the odds of ROSC and neurologically intact survival were 1.02 (95% CI: 0.99, 1.05) and 1.03 (95% CI: 0.98, 1.08), respectively. CONCLUSIONS: When adjusted for Utstein variables and CPR quality metrics, CCRV was not significantly associated with outcomes from OHCA. Our findings may have been impacted by the sample size of our study.
Correlation of 5-year survival and cure in NSCLC: An analysis of delayed cancer deaths in long-term survivors of NSCLC.
Authors: M. O. Hubbard, P. Fu, J. L. Worthington, A. Dowlati, P. A. Linden
Journal: Journal of Clinical Oncology (2010)

6134 Background: Five-year survival following the diagnosis of non small cell lung cancer (NSCLC) has been equated with a cure. Because so few (15%) NSCLC patients survive five years, data on long term survivors is lacking. The Surveillance, Epidemiology, and End Results (SEER) database was employed to investigate the death rate and cause of death in NSCLC patients alive at least 5 years after diagnosis. Methods: A total of 29,002 adult patients alive five years after diagnosis of NSCLC registered in the SEER database from 1988 to 2001 were examined. Variables recorded include age, sex, tumor histology, TNM stage, and surgery performed. Primary endpoints were overall survival (OS), and disease specific survival (DSS) defined as death with NSCLC as the documented cause of death. Survival analysis was performed with Kaplan-Meier estimates and multivariable Cox proportional hazards regression. Results: A total of 13,945 men and 15,057 women (mean ± SD age, 64.4 ± 10.6 years) with NSCLC were analyzed. OS at 10 years was 57.4%, at 15 years was 34.7%, and at 18 years was 25.7%. DSS at 10 years was 78.4%, at 15 years was 67.5%, and at 18 years was 61.7%. Squamous cell (HR 0.881) and large cell (HR 0.806) histologies have a DSS advantage (p < 0.0005) compared to adenocarcinoma. Pneumonectomy (HR 0.453), lobectomy (HR 0.495), and sublobar resection (HR 0.746) were all statistically superior in DSS than no surgery (p < 0.0001). Compared to stage IA, DSS of stage IB (HR 1.172), IIA (1.796), IIB (1.547), IIIA (1.972), IIIB (1.788), and IV (2.204) were all inferior (p < 0.0001). Conclusions: Five-year survivors from NSCLC have a persistent risk of death from lung cancer up to 18 years from diagnosis. Surgical resection and nonadenocarcinoma histology are associated with better disease specific survival. Although the rate of death from NSCLC decreases with time, significant numbers of patients die from lung cancer as long as 18 years after initial diagnosis. No significant financial relationships to disclose.
The sensitivity and specificity of pseudomonas aeruginosa detection using hydrogen cyanide concentration in exhaled breath – The SPACE study
Authors: Francis Gilchrist, Andrew Jones, Kevin Webb, David Smith, Warren Lenney
Journal: European Respiratory Journal (2014)

Introduction   Hydrogen cyanide (HCN) is an in-vitro marker of  Pseudomonas aeruginosa  (PA). This is the first in-vivo study to investigate if HCN is an early marker of PA infection in children with cystic fibrosis (CF).   Methods   Children who had not grown PA in the last year were recruited from 8 CF centres. At each CF appointment for the next 2 years they provided an exhaled breath sample and completed a questionnaire about symptoms and antibiotic use. The HCN concentration of the breath sample was analysed using selected ion flow tube mass spectrometry. At study completion the results of the routine microbiology samples were compared to the HCN concentrations.   Results   233 children were recruited, median (IQR) age: 8 (5.0-12.2) years. The median duration of follow-up was 2.0 (1.7-2.3) years with a total of 2086 clinic visits and 2072 breath samples. The median number of breath samples per child was 9 (6-12). There were 71 new PA isolates with an incidence of 0.19 cases per patient year. A study visit (with proforma and breath sample) had been completed within 7 days (+/-) of the culture result for 57 of the new PA isolates. 24/57 (42%) children were asymptomatic at the time of the PA isolate. An elevated HCN concentration (>5ppb) was present in 28/57 breath samples (sensitivity 49%). In 5 children the elevated HCN concentration preceded the PA culture by > 2 months. 8 children who did not isolate PA had an elevated HCN at some point (specificity 95%).   Conclusions   In children with CF, an elevated HCN concentration in exhaled breath is a specific marker of PA infection. Further studies are required to investigate if the sensitivity can be improved.
Does the sequence of stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) affect treatment related morbidity in melanoma patients with brain metastasis?
Authors: H. Kaur, J. Suh, M. Vogelbaum, G. H. Barnett, P. Elson, T. E. Olencki
Journal: Journal of Clinical Oncology (2004)

7564 Background: For melanoma patients who develop brain metastasis, the use of SRS has become a popular option given the ease of administration and efficacy. The potential side effects of SRS have not been well documented. The purpose of this study was to determine if the sequence of SRS to WBRT affected toxicity. Methods: From January 1996 to June 2003, 33 melanoma patients (17 males and 16 females) who underwent SRS for newly diagnosed brain metastasis were retrospectively reviewed. These patients were part of an Institutional Review Board approved brain metastasis database. New neurological deficits, seizures, or the need for steroids for more than 8 weeks post-therapy were considered adverse events. The patients were grouped into 3 categories: SRS alone (SRS), WBRT followed by SRS (WBRT-SRS), and SRS followed by WBRT (SRS-WBRT). Results: The table summarizes the post-therapy adverse events. Patients with multiple lesions were more likely to have received WBRT-SRS (p=.06). 7/33 (21%) patients had multiple events. At the time of analysis, 30/33 (91%) patients had died (median survival of 6.3 months). Using multivariate analysis of gender, age, number of brain metastasis, performance status, LDH, and type of therapy, only the number of brain metastasis had an impact on overall survival (p=. 002). Conclusions: The incidence of neurologic deficits, seizures, or prolonged steroid use was common in melanoma patients with brain metastasis treated by SRS with or without WBRT. Given the small size, it was difficult to determine if the timing of SRS or the use of WBRT affected toxicity. We recommend that prospective analysis of treatment-related toxicity be performed to determine the true extent of these toxicities. No significant financial relationships to disclose.
WITHDRAWN: Protective effect of 1,25-dihydroxyvitamin D3 on concanavalin A-induced mouse hepatitis
Authors: Jing Bi, Hitoshi Maeda, Rui Fujimura, Hiroshi Watanabe, Yu Ishima, Masaki Otagiri, Toru Maruyama
Journal: Asian Journal of Pharmaceutical Sciences (2015)

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