tbuckley/cabot-search huggingface dataset:
Early results from a novel treatment strategy for chemotherapy-related anemia: Epoetin alfa 60,000 U SC QW induction followed by 60,000 U SC Q2W
Authors: S. Tarantolo, D. W. Bouda
Journal: Journal of Clinical Oncology (2004)

8204 Background: Epoetin alfa (EPO) 40,000 U subcutaneously (SC) once weekly (QW) significantly reduces transfusions, increases hemoglobin (Hb), and improves overall quality of life in anemic cancer patients (pts) receiving chemotherapy (CT). Higher QW initiation doses may improve hematologic response (HR) rates by stimulating erythropoiesis, allowing less frequent dosing. Methods: This ongoing, open-label, pilot study (N = 50) is investigating the efficacy and safety of a 4-week (wk) induction treatment (Phase A, EPO 60,000 U SC QW) followed by 12-wk maintenance (Phase B, EPO 60,000 U SC every 2 wks [Q2W]) in pts with anemia (Hb ≤11 g/dL) undergoing CT for nonmyeloid malignancies. Primary end point is proportion of pts achieving HR (≥1 g/dL Hb increase from baseline [BL]) in Phase A. Pts are withdrawn for Hb increase <1 g/dL (Phase A) or Hb decrease ≥2 g/dL (Phase B). If Hb >13 g/dL or if increase is >1.3 g/dL in 2 wks, EPO is held until Hb ≤12 g/dL, then resumed at 40,000 U SC in Phase A or B. Preliminary efficacy results are reported for Phase A. Results: Twenty-four pts receiving ≥1 dose of study drug are included in this analysis (mean age 66 y [range 39–80]; 33% men; 83% ECOG PS 0–1, BL Hb 10.1 ± 0.8 g/dL). EPO dose was reduced to 40,000 U QW in 2 pts. Available Hb results are shown in table. At the time of this analysis, 12/24 (50%) pts achieved HR independent of transfusion; mean time to HR was 11 ± 5 days (median 8 days). No pts were transfused. Three pts withdrew in Phase A (1 adverse event [AEs], 1 pt withdrew consent, 1 pt missed dose). There were 2 deaths unrelated to EPO (sepsis and disease progression). Conclusions: Preliminary Phase A results suggest that EPO 60,000 U QW is well tolerated. NCCN guidelines (Cancer- and Treatment-related anemia) define Hb response as a 1-g/dL increase after 4 wks; these preliminary data show an earlier 1-g/dL increase in Hb. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech Products, L.P. Johnson & Johnson Johnson & Johnson Ortho Biotech
Identifying genetic susceptibility to isoniazid- induced hepatitis
Authors: Maria Alcobia, Maria Carvalho, Miguel Villar, Luis Mesquita, Carlos Cordeiro, Fontes Ribeiro, Henriqueta Coimbra
Journal: European Respiratory Journal (2013)

Isoniazid (INH)- induced hepatitis can be fatal. The identification of risk genotypes offers the possibility of therapy individualization and may decrease the frequency of this complication. This study aimed to evaluate the association of polymorphisms of genes involved in INH metabolism or related with hepatocyte response to chemical-induced stress, with the susceptibility to INH-induced hepatitis.

Materials and methods: A total of 109 treated tuberculosis patients, were studied. Ten polymorphisms of NAT2 were genotyped by sequencing; polymorphisms of CYP2E1 (rs6413432 and rs2031920) and ABCB11 (rs2287622) were analyzed by PCR - RFLP assay and homozygous for GSTM1 and GSTT1 deletions were identified by PCR multiplex.

Results: Clinical variables such as age, alcoholic habits or previous hepatitis, were not associated with the occurrence of INH-induced hepatitis. Slow acetylators (52.3%) identified by NAT2 genotyping were significantly more prone to develop hepatotoxicity ( p = 0.01; OR = 3; 95% CI = 1.23-7.35). Polymorphisms of CYP2E1 , GSTM1 and GSTT1 were not associated with the phenotype. For ABCB11 polymorphism, homozygous for variant Ala had increased risk of developing hepatotoxicity (OR = 2.1; 95% CI = 0.9-5), though not reaching statistical significance. This effect was more evident for females than for males (OR = 2.19; CI = 0.45-10.58).

Conclusion: NAT2 genotyping contributes to identify susceptible patients to INH-induced hepatitis. Prospective studies will define genotyping contribution to the reduction of this infrequent but fearsome complication. Polymorphism in ABCB11 gene deserves further investigation, especially among women.
Ebola outbreak exposed major weakness in UK handling of health emergencies
Authors: Adrian O’Dowd
Journal: BMJ (2016)

The United Kingdom has “serious weaknesses” in its ability to handle and respond to infectious disease emergencies, MPs have warned.

Slowness to respond, poor coordination among various expert bodies, delays in organising research, and a lack of speed in manufacturing vaccines were all exposed by the recent outbreak of Ebola virus disease in west Africa, says a report by the House of Commons Science and Technology Committee.1

The committee praised the government for its “leading contribution” to the fight against the disease in west Africa and for the practical support it provided in building and staffing treatment centres and deploying troops, helicopters, and an aviation support ship.

The west African outbreak, which began in late 2013 but …
춘계학술대회 : 포스터전시 ; 마크로아밀레이스혈증 1예
Authors: 유금혜, 김태헌, 유권, 강은숙, 오희정, 송지현, 송현주, 염혜정, 김성은, 심기남, 정성애, 신수연, 정혜경, 문일환
Journal: Clinical and Molecular Hepatology (2005)

배경: 췌장이나 타액선의 질환이 없으면서 혈중 아밀라제치의 상승이 나타나는 드문 원인으로 마크로아밀라제혈증이 알려져있다. 마크로아밀라제혈증에서는 아밀라아제가 혈청 단백질과 결합하여 만들어진 복합체로 존재하여 혈액에서 신장으로의 여과가 아주 느린 특징을 나타낸다. 1967년 Berk 등이 처음 보고한 이후 세계적으로 다수의 증례가 보고 되고 있으나 적극적인 관심의 부족으로 인하여 국내 보고는 드물었다. 저자들은 우연히 발견된 지속적인 고아밀라제혈증으로 내
Prospective evaluation of pulmonary function in patients with breast cancer on dose-dense chemotherapy
Authors: R. Yerushalmi, M. Kramer, S. Rizel, A. Sulkes, K. A. Gelmon, T. Granot, S. M. Stemmer
Journal: Journal of Clinical Oncology (2008)

558 Background: Dose-dense chemotherapy (DDC) is widely used in the adjuvant setting for high-risk breast cancer patients. After several patients complained of symptomatic dyspnea, we embarked on a prospective study to evaluate the incidence, objective findings, and possible association with DDC. Methods: Thirty-four consecutive patients with normal chest CT or X-ray were recruited from Sept 2006 to Apr 2007 at RMC. DDC consisted of I.V. doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 (AC) q 14 daysX4 with growth-factor support followed by weekly I.V. Paclitaxel 80mg/m2 x12. The following parameters were prospectively evaluated at 3 time points. (P1- before AC, P2-end of AC and P3-end of treatment): symptomatic dyspnea, blood pressure, pulse/min, hemoglobin (Hb), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), cardiac ejection fraction (EF), pulmonary function tests including spirometry, lung volume, and diffusion capacity (DLCO, adjusted to Hb levels). The differences between the three time points (P1, P2, P3) were examined for each of the parameters using repeated measurement analysis for the overall difference and paired t tests for differences between consecutive time points. Data was expressed as mean±SD. Results: Although only 5 patients (15%) complained of dyspnea, in 90.6% of the patients there was a 29% reduction in mean DLCO between P1 and P2 and in 100 % of the patients a 34% decline between time P1 and P3 (p<10-3 ). Neither age nor smoking correlated with these changes. No change in EF was observed (p=0.54). There were significant changes in Hb (13.4, 11.6, 11.6, p<10-3), CRP (0.25, 0.91, 1.55 p=0.024), ESR (19.4, 42.2, 33.6 p<10 -3 ) and FVCins levels (p=0.034). Conclusions: DDC significantly reduces DLCO. Confirmation in larger studies with longer follow-up as well as an understanding of the etiology is needed. However, awareness of this newly described toxicity could be important in women with preexisting lung disease. Sig (2-tailed) Paired differences 95% confidence interval of the difference DCLO Mean ml/min/mmHg Std. Deviation Std. error mean Lower Upper Point 1–2 6.32 4.84 0.85 4.58 8.06 0.000 Point 1–3 7.16 3.34 0.62 5.89 8.44 0.000 Point 2–3 0.97 3.84 0.73 -0.52 2.46 0.193 No significant financial relationships to disclose.
The Combination of DNA Ploidy Status and PTEN/6q15 Deletions Provides Strong and Independent Prognostic Information in Prostate Cancer
Authors: Maximilian Lennartz, Sarah Minner, Sophie Brasch, Hilko Wittmann, Leonard Paterna, Katja Angermeier, Eray Öztürk, Rami Shihada, Mingu Ruge, Martina Kluth, Christina Koop, Waldemar Wilczak, Till Krech, Patrick Lebok, Corinna Wittmer, Hans Heinzer, Thomas Steuber, Meike Adam, Hartwig Huland, Markus Graefen, Alexander Haese, Ronald Simon, Guido Sauter, Thorsten Schlomm
Journal: Clinical Cancer Research (2016)

Aberrant DNA content has been discussed as a potential prognostic feature in prostate cancer.We analyzed the clinical significance of DNA ploidy in combination with prognostic relevant deletions of PTEN and 6q15 in 3,845 prostate cancers.The DNA status was diploid in 67.8%, tetraploid in 25.6%, and aneuploid in 6.8% of tumors, and deletions of PTEN and 6q15 occurred in 17.8% and 20.3% of tumors. Abnormal DNA content and deletions were linked to high Gleason score, advanced tumor stage, and positive nodal stage (P < 0.0001 each). The risk of PSA recurrence increased from diploid to tetraploid and from tetraploid to aneuploid DNA status (P < 0.0001 each). However, 40% of patients with Gleason score ≥4+4 and 55% of patients with PSA recurrence had diploid cancers. This fraction decreased to 21% (Gleason ≥4+4) and 29% (PSA recurrence) if PTEN and/or 6q deletion data were added to ploidy data to identify cancers with an aberrant DNA status. The significance of combining both deletions and ploidy was further demonstrated in a combined recurrence analysis. Presence of deletions increased the risk of PSA recurrence in diploid (P < 0.0001), tetraploid (P < 0.0001), and aneuploid cancers (P = 0.0049), and the combination of ploidy data and deletions provided clinically relevant information beyond the CAPRA-S nomogram. Multivariate modeling including preoperatively and postoperatively available parameters identified the "combined DNA status" as a strong independent predictor of poor patient outcome.The combinatorial DNA content analysis involving general (ploidy) and specific events (deletions) has the potential for clinical utility in prostate cancer. Clin Cancer Res; 22(11); 2802-11. ©2016 AACR.
The kidney triggers graft-versus-host disease in experimental combined transplantation of kidney and stem cell-enriched peripheral leukocytes.
Authors: N Perico, S Amuchastegui, M Bontempelli, G Remuzzi
Journal: Journal of the American Society of Nephrology (1996)

As a preclinical step to human studies with combined stem cell-enriched peripheral leukocytes and organ transplantation from the same donor, a series of studies in rats was undertaken. These studies indicated that Lewis rats infused intravenously with major histocompatibility complex-incompatible (from Brown-Norway rats), stem cell-enriched peripheral leukocyte preparation alone never developed graft-versus-host disease (GHVD). However, GVHD invariably manifested in all animals a few days after the kidney was transplanted in rats that had been previously primed with stem cell-enriched peripheral leukocytes from the same kidney donor strain. GVHD was prevented by substituting the crude preparation of stem cell-enriched peripheral leukocytes with a purified preparation that was almost completely free of T lymphocytes. However, in these latter experiments all rats rejected their kidney graft within 10 days from the surgery. In rats previously given the crude stem cell-enriched peripheral leukocyte preparation, perioperative administration of the fusion protein CTLA4lg also prevented GVHD and prolonged kidney graft survival up to 106 to 175 days. By contrast, animals with kidney transplants, which were given CTLA4lg without stem cells, rejected their grafts within 35 days. All together, these findings may possibly contribute to the creation of rationally designed strategies of combining organ and bone marrow from the same donor to enhance mixed chimerism and prolong survival after organ transplantation.
Elevated Serum Levels Of Von Willebrand Factor (vWF) Predict For Early Death and Shorter Survival In Patients With Primary Systemic Light Chain (AL) Amyloidosis Independently Of Cardiac Biomarkers
Authors: Efstathios Kastritis, Ioannis Papassotiriou, Evangelos Terpos, Alexandra Gougoutsi, Nikolaos Simos, Nikolaos Kanellias, Evangelos Eleutherakis-Papaiakovou, Dimitrios Chiotis, Georgios Amentas, Maria Kavasi, Constantinos Pamboucas, Erasmia Psimenou, Savvas Th. Toumanidis, Maria Roussou, Meletios A. Dimopoulos
Journal: Blood (2013)
Breast cancer in young women age &lt; 36 years: A retrospective analysis of prognostic factors in 926 patients in 8 french instituitions. GETNA group
Authors: J. Gligorov, M. N. Guilhaume, M. Spielmann, E. Luporsi, B. Asselain, S. Rivera, F. Penault-Llorca, L. Aimard, P. Pouillart, M. Namer
Journal: Journal of Clinical Oncology (2005)

9685 Background: Age ≤35 years is considered as a bad prognostic factor in women with breast cancer (BC). Methods: Clinical and pathological data of 926 women ≤35 years with invasive non metastatic BC, consecutively treated between 1990–99 in 8 french institutions were analysed. Clinical and pathological size, node involvement, histological type, SBR histological grading, hormone receptors (HR), and treatment characteristics were analysed for all patients. Distant Recurrence Free Survival (DRFS) and overall survival (OS) were analysed using Kaplan Meier estimates and comparisons were made using the logrank test. Multivariate analyses were carried out using Cox hazards model. Results: With a median FU of 87 months,239 deaths, 177 loco-regional and 323 distant recurrences were observed. Five and 10 years survival rates were 82.2% and 66.5%. Five and 10 years DRFS rates were 67.2% and 50.8%. No difference was observed according to age (≤30 years old, 31–33 and 34–35, p = 0.74) neither in DRFS nor in OS (p=0.99 and p = 0.74). Compared to T1, T2 was associated with a RR of 1.65 [1.23–2.22], and T3/T4 with a RR of 2.73 [1.92–3.88] for the OS (p<10-4) and T2 was associated with a RR of 1.57 [1.23–2.02], and T3/T4 with a RR of 2.25 [1.65–3.07] for the DRFS (p<10-4). Compared to negative node involvement, pN1 status was associated with a RR of 2.22 [1.60–3.09], and pN2 with a RR of 4.35 [3.14–6.03] in OS (p<10-4) and pN1 nodes involved was associated with a RR of 2.64 [2.01–3.47], and 4 and more with a RR of 4.22 [3.17–5.62] for the DRFS (p<10-4). Compared to positive HR, negative HR were respectively associated with a RR of 1.37 [1.05–1.82] (p=0.019), and 1.49 [1.14–1.96] (p<10-2) in OS. But no difference was observed according to HR in DRFS. Compared to grade I in SBR, grade II and III were respectively associated with a RR of 2.40 [1.35–4.27], and 2.61 [1.46–4.65] for the OS (p<10-3) and a RR of 1.86 [1.20–2.89], and 1.75 [1.12–2.72] in DRFS (p<10-3). Multivariate analysis results will be presented during the meeting. Conclusions: In these retrospective analyses, the most important prognostic factor for YA with breast cancer is tumour size followed by pathological grade (SBR), pN and HR status. No significant financial relationships to disclose.
Influenza-Related Hospitalizations and Poverty Levels — United States, 2010–2012
Authors: James L. Hadler, Kimberly Yousey-Hindes, Alejandro Pérez, Evan J. Anderson, Marisa Bargsten, Susan R. Bohm, Mary Hill, Brenna Hogan, Matt Laidler, Mary Lou Lindegren, Krista L. Lung, Elizabeth Mermel, Lisa Miller, Craig Morin, Erin Parker, Shelley M. Zansky, Sandra S. Chaves
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Annual influenza vaccine is recommended for all persons aged ≥6 months in the United States, with recognition that some persons are at risk for more severe disease (1). However, there might be previously unrecognized demographic groups that also experience higher rates of serious influenza-related disease that could benefit from enhanced vaccination efforts. Socioeconomic status (SES) measures that are area-based can be used to define demographic groups when individual SES data are not available (2). Previous surveillance data analyses in limited geographic areas indicated that influenza-related hospitalization incidence was higher for persons residing in census tracts that included a higher percentage of persons living below the federal poverty level (3-5). To determine whether this association occurs elsewhere, influenza hospitalization data collected in 14 FluSurv-NET sites covering 27 million persons during the 2010-11 and 2011-12 influenza seasons were analyzed. The age-adjusted incidence of influenza-related hospitalizations per 100,000 person-years in high poverty (≥20% of persons living below the federal poverty level) census tracts was 21.5 (95% confidence interval [CI]: 20.7-22.4), nearly twice the incidence in low poverty (<5% of persons living below the federal poverty level) census tracts (10.9, 95% CI: 10.3-11.4). This relationship was observed in each surveillance site, among children and adults, and across racial/ethnic groups. These findings suggest that persons living in poorer census tracts should be targeted for enhanced influenza vaccination outreach and clinicians serving these persons should be made aware of current recommendations for use of antiviral agents to treat influenza (6).
Abstract 9852: T Lymphocyte Depletion Following Primary Percutaneous Coronary Intervention Predicts Infarct Size and Ischemia Reperfusion Injury
Authors: Stephen Boag, Evgeniya Shmeleva, Rajiv Das, Mohaned Egred, Azfar Zaman, Alan Bagnall, Andrew Owens, Bernard Keavney, Ioakim Spyridopoulos
Journal: Circulation (2013)

Background: We have previously demonstrated acute changes in lymphocyte numbers in peripheral blood following reperfusion with primary percutaneous coronary intervention (PPCI) for STEMI. The goal of this study was to investigate a potential role for T cells in ischemia reperfusion (I/R) injury. Methods: We analyzed blood from 22 STEMI patients undergoing PPCI. Blood was taken at the start of the procedure, and at 15, 30, 90 minutes, and 24 hours post reperfusion. In 5 patients with infarcts due to LAD occlusion, coronary sinus (CS) blood was also obtained 30-60min after reperfusion along with simultaneous aortic blood. 8-colour flow cytometric analysis was performed on the fresh blood to quantify lymphocyte populations. Cardiac MRI was performed at 1-7 days, and left ventricular ejection fraction, infarct size (measured by late gadolinium enhancement), microvascular obstruction (MVO), area at risk and salvage index quantified. Results: T-lymphocytes dropped between 0 and 90 minutes by a mean of 42% (0min mean 1767/μl, 90min 931/μl), CD4 T-helper cells by 31%, and CD8 cytotoxic T-cells by 55%. The change in total T-cells correlated with infarct size (r=-0.78, p&lt;0.001), as did that of CD4 (r=-0.66, p&lt;0.01) and CD8 T cells (r=-0.76, p&lt;0.001). The T cell drop between 0 and 90 minutes also correlated strongly with MVO (r=-0.72, p&lt;0.01), as did the CD4 (r=-0.66, p&lt;0.01) and CD8 T cell drop (r=-0.77, p&lt;0.001). Myocardial salvage index correlated strongly with the change in T cells (r=0.85, p&lt;0.001), CD4 T cells (r=0.76, p&lt;0.01) and CD8 T cells (r=0.76, p&lt;0.01) between 30 and 90 minutes. Prior to reperfusion 6.4% of CD8 T cells were activated (CD69+), with progressive loss of CD69+ cells after 90 minutes (4.3%) and 24 hours (2.6%, 0min vs 24hr p&lt;0.01). However, CS sampling showed an increase in CD69 expression between aortic and CS blood, suggesting activation of T cells as they pass through the myocardial vascular bed. Conclusion: Acute changes in T lymphocyte numbers following reperfusion after PPCI predict infarct size, MVO, and salvage index. The drop in these cells following reperfusion, and the dynamics of CD69 expression, suggest a potential role for CD69+ activated T cells in I/R injury. This requires further investigation and may represent a novel therapeutic target.
Activity of patupilone for the treatment of recurrent or progressive brain metastases in patients (pts) with non-small cell lung cancer (NSCLC): An open-label, multicenter, phase II study
Authors: L. Abrey, P. Y. Wen, R. Govindan, H. J. Reimers, J. R. Rigas, H. I. Robins, S. de Bedout, C. O’Connell, X. Li, A. Johri
Journal: Journal of Clinical Oncology (2007)

18058 Background: Advances in systemic chemotherapy have improved overall survival for patients with advanced NSCLC; unfortunately, CNS metastasis is common and limits survival benefits with current therapies. Unlike taxanes, preclinical findings suggest that the novel epothilone, patupilone, crosses the blood-brain barrier in 3 animal species and also has antitumor effects in brain tumor models. Results of an ongoing phase I/II study of patupilone as second-line therapy in pts with NSCLC are encouraging. The present study is evaluating the efficacy of patupilone in pts with brain metastases from NSCLC who have failed or recurred after previous chemotherapy, surgery, and/or radiation to the brain. Methods: This open-label, single-arm, multicenter, phase II study has a 2-stage design (25 pts per stage). Eligible pts have histologically confirmed NSCLC and = 1 recurrent, bidimensionally measurable intracranial lesion = 2 cm. Patupilone was administered IV at 10 mg/m 2 as a single 20-min IV infusion every 3 weeks until disease progression, satisfactory response, or unacceptable toxicity. The primary multinomial endpoint was a combination of early progression (disease progression or death before cycle 1, day 21) and response rate (alive without progression at cycle 4, day 1). Results: An interim analysis of 13 pts with a median age of 62 years (range, 40–67 years) is reported. The most common adverse events (AEs) related to study drug were NCI CTC grade 1/2 diarrhea in 7 (54%) pts, nausea in 3 (23%), and fatigue in 2 (15%). Only 2 serious AEs (grade 4 colitis and grade 3 diarrhea) and 2 additional grade 3 AEs (diarrhea, neutropenia) were reported in 1 pt each. Three (23%) pts experienced early disease progression. Five (38%) pts responded, receiving a median 10 cycles (range, 5 to 12 cycles) and were alive without progression on cycle 4, day 1. Conclusions: Patupilone has activity in patients with CNS metastases from advanced NSCLC and is well tolerated. Additional investigation of patupilone as a treatment for brain metastases from NSCLC is warranted. [Table: see text]