tbuckley/cabot-search huggingface dataset:
Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab
Authors: P.F. Ferrucci, P.A. Ascierto, J. Pigozzo, M. Del Vecchio, M. Maio, G.C. Antonini Cappellini, M. Guidoboni, P. Queirolo, P. Savoia, M. Mandalà, E. Simeone, S. Valpione, M. Altomonte, F. Spagnolo, E. Cocorocchio, S. Gandini, D. Giannarelli, C. Martinoli
Journal: Annals of Oncology (2016)

Clinical responses to ipilimumab are variable in terms of onset, magnitude and duration. Upfront identification of patients who are more likely or unlikely to benefit from treatment is a major need.Prospectively collected data from 720 advanced melanoma patients treated with ipilimumab 3 mg/kg within the Italian expanded access program were analyzed. The derived neutrophil-to-lymphocyte ratio (dNLR) was calculated from baseline peripheral blood cell counts, and receiver operating characteristic curve was used to evaluate the best cutoff for this marker. Patients were stratified according to dichotomized baseline absolute neutrophil counts (ANC), dNLR and their combination. The prognostic values of ANC and dNLR for survival were assessed using multivariate Cox proportional hazard models. A subgroup analysis including LDH in the models was also carried out.The median follow-up was 16.5 months. The optimal cutoff for dNLR was 3. Baseline ANC and dNLR were significantly associated with the outcome of ipilimumab-treated melanoma patients, in terms of disease progression and death (P < 0.0001 for all). Furthermore, for each elevated variable, prognosis worsened. Patients with both ANC ≥ 7500 and dNLR ≥ 3 had a significantly and independently increased risk of death [hazard ratio(HR) = 5.76; 95% confidence interval (CI) 4.29-7.75] and of progression (HR = 4.10; 95% CI 3.08-5.46) compared with patients with both lower ANC and dNLR. Patients with one of the two factors elevated displayed an intermediate risk of progression and death. The 1- and 2-year survival rates were 2% and 0%, respectively, for patients with ANC ≥ 7500 and dNLR ≥ 3, and 43% and 24%, respectively, for patients with both lower ANC and dNLR.Although these findings need to be confirmed and validated, we suggest that a neutrophil-based index may help risk-group stratification and assist disease-management strategies. Furthermore, the potential predictive value of this index for response to ipilimumab should be investigated in randomized clinical trials.
Abstract 16762: Predictors of Neurologic Outcomes after Ventricular Fibrillation with Out-Of-Hospital Cardiac Arrest Witnessed by Emergency Medical Service Personnel
Authors: Jun Matsumoto, Yoshio Tahara, Naoto Morimura, Kazuo Kimura, Yasufumi Oi, Taku Iwami, Hideharu Tanaka, Naohiro Yonemoto, Hiroshi Nonogi, Takeshi Kimura, Ken Nagao
Journal: Circulation (2012)

Background: In Japan, advanced interventions that can be performed by emergency medical service (EMS) personnel in patients with out-of-hospital cardiac arrest (OHCA) are defibrillation, advanced a...
Phenytoin for neuroprotection in patients with acute optic neuritis: a randomised, placebo-controlled, phase 2 trial
Authors: Rhian Raftopoulos, Simon J Hickman, Ahmed Toosy, Basil Sharrack, Shahrukh Mallik, David Paling, Daniel R Altmann, Marios C Yiannakas, Prasad Malladi, Rose Sheridan, Ptolemaios G Sarrigiannis, Nigel Hoggard, Martin Koltzenburg, Claudia A M Gandini Wheeler-Kingshott, Klaus Schmierer, Gavin Giovannoni, David H Miller, Raju Kapoor
Journal: The Lancet Neurology (2016)
Fractionated Cyclophosphamide and Etoposide for Children With Advanced or Refractory Solid Tumors: A Phase II Window Study
Authors: Elpis Mantadakis, Larry Herrera, Patrick J. Leavey, Robert O. Bash, Naomi J. Winick, Barton A. Kamen
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Cyclophosphamide (CPA) has a broad spectrum of activity against solid tumors. Hepatic self-induction of the active metabolite 4-hydroxycyclophosphamide occurs after repeated administration. We evaluated the clinical efficacy of a window regimen that administers fractionated CPA in conjunction with etoposide (VP16) in children with advanced or refractory solid tumors. PATIENTS AND METHODS: Seventeen children with advanced (n = 12) or refractory (n = 5) solid tumors were entered onto this phase II window study. The treatment regimen consisted of intravenous (IV) CPA 500 mg/m 2 /d and IV VP16 100 mg/m 2 /d. Both drugs were administered daily by short infusions for 5 consecutive days. RESULTS: A total of 34 courses were administered, with a median of two courses per patient. The median interval between chemotherapy courses was 21 days (range, 17 to 35 days). Thirty-three courses were assessable for toxicity, and all patients were assessable for response. No life-threatening toxicities were observed. The incidence of grade 3 or 4 neutropenia was 94% and of fever and neutropenia 38%. Fever and neutropenia occurred after 12 of 26 courses without recombinant human granulocyte colony-stimulating factor (rhG-CSF) and after one of eight courses with rhG-CSF (P = .09). Grade 3 or 4 thrombocytopenia occurred after 10 courses (29%). There were no positive blood cultures. One heavily pretreated patient developed a localized perirectal abscess that required drainage. There were 10 patients (59%) with partial responses, four (23.5%) with stable disease, and three with progressive disease. CONCLUSION: Fractionated IV CPA and VP16 over 5 days can be safely administered in children with advanced or refractory solid tumors and has notable antineoplastic activity.
Incidence and risk factors for development of skin breakdown in patients undergoing prolonged noninvasive ventilation: A case-control study
Authors: Wellington Yamaguti, Thelma Gomes, Eliana Moderno, Sandra Yamashita, Cláudia Kondo, Ana Maida, Christina Brito
Journal: European Respiratory Journal (2012)

Among the adverse effects related to the mask, skin breakdown is a frequent complication and its occurrence may increase patient discomfort and failure of noninvasive ventilation (NIV). This study aimed to quantify the incidence and identify potential risk factors for the development of skin breakdown in patients undergoing prolonged NIV. A retrospective, observational study was conducted in the adult intensive care unit of a general hospital. It included 375 patients (between January and December 2011) receiving at least one application of NIV for a period longer than two hours. Cases were subjects who developed skin breakdown and controls were those who did not developed it. The risk factors evaluated were: age, gender, interface, number of applications carried out for more than 2 hours (N>2h), average time of use per application, total time of NIV use, inspiratory and expiratory pressure titrated, and delta pressure. Of the included patients, 49 (13.1%) developed skin breakdown Stage I and 5 patients (1.33%) developed skin breakdown Stage II. Case group presented a higher face mask use (92.6%) than control group (21.5%) (p 2h in case group was 7.1 ± 13.3 and in control group was 4.4 ± 7.5 (p=0.03). Finally, the total time of NIV use was higher in case group (44.6 ± 118.5 h) compared to control group (21.8 ± 45.5 h) (p=0.01). We recommend the use of total face mask in patients expected to use NIV for a period longer than two hours in order to prevent the development of skin breakdown.
Improving the final year of life at the institutional level: Quality dying initiative (QDI).
Authors: Jeff Myers, Tracey DasGupta
Journal: Journal of Clinical Oncology (2014)

124 Background: For a tertiary academic health sciences and comprehensive cancer centre, care of the dying is a significant element of the institution’s overall patient and family care experience. The aim for this large-scale quality improvement project was to improve the quality of the experience for a patient in the final year of life and their family members. Methods: This is descriptive study involves one institution and the characterization of three distinct patient populations: A - Imminently dying patients for whom care goals have been clarified to be comfort, B - Patients for whom death “this admission” would not be a surprise and C - Among patients being discharged, death “within the next year” would not be a surprise, linking in the outpatient cancer care setting. Results: On average 19 deaths per week are in some way expected for the institution’s acute care setting. Phase 1 of the QDI included a review of evidence and best practices in care of the dying as well as comprehensive plans for both organizational engagement and communications. Phase 2 of the QDI (i.e. “Implementation Phase”) involved interventions for each patient population. A corporate-wide “Comfort Strategy” was developed to address Population A. Components include standardized order sets, standardized interprofessional “Comfort Assessment and Documentation”, the palliative care team’s “Coaching Consult”, a “Family Member Education” process and an evaluation plan that includes an experience survey routinely sent to family members following a patient’s death. The intervention was piloted on and subsequently rolled out to all inpatient oncology units. Interventions for Population B and C are the triggering of Goals of Care and Advance Care Plan discussions respectively. Key metrics have been identified for all three patient populations and are based on care elements considered important by dying patients and their family members. These now comprise a dashboard, which has been endorsed for roll out to all patient care units in the acute care setting. Conclusions: A quality framework can be effectively applied for the institutional context of developing an approach to improving the final year of life for a cancer patient.
Treatment of hepatosplenic candidiasis with liposomal-amphotericin B.
Authors: G Lopez-Berestein, G P Bodey, L S Frankel, K Mehta
Journal: Journal of Clinical Oncology (1987)

Nine patients with hematologic malignancies developed fungal infections, predominantly involving the liver and spleen. Eight patients had biopsy-documented progressive candidiasis and one had an unclassified fungus. The patients were treated with liposomal-amphotericin B (L-AmpB) after their fungal infection progressed during treatment with standard intravenous (IV) AmpB (Fungizone; E. R. Squibb &amp; Son, Princeton, NJ) and/or other antifungals. Eight patients (88.8%) were cured of their fungal infection, and one showed improvement after treatment. Minor acute toxicity and no chronic toxicity were associated with the administration of L-AmpB. L-AmpB is a safe and effective therapeutic method for treating fungal infections that have invaded the liver and spleen even when they are refractory to conventional anti-fungal therapy.
Cisplatin nephrotoxicity: diethyldithiocarbamate, WR2721, or just water?
Authors: E Cvitkovic, D M Hayes, R B Golbey, I H Krakoff
Journal: Journal of Clinical Oncology (1991)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1991.9.4.707 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 1648600 Cisplatin nephrotoxicity: diethyldithiocarbamate, WR2721, or just water? E CvitkovicxE CvitkovicSearch for articles by this author , D M HayesxD M HayesSearch for articles by this author , R B GolbeyxR B GolbeySearch for articles by this author , I H KrakoffxI H KrakoffSearch for articles by this author https://doi.org/10.1200/JCO.1991.9.4.707 First Page PDF © 1991 by American Society of Clinical Oncology
Physician-Assisted Dying
Authors: Lawrence O. Gostin, Anna E. Roberts
Journal: JAMA (2016)

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Abstract 14554: Effect of Periprocedural Glycemic Control on Platelet Activity in Patients with Type 2 Diabetes Mellitus Undergoing Coronary Angiography
Authors: Binita Shah, Jeffrey S Berger, Nicholas S Amoroso, Xingchen Mai, Jeffrey D Lorin, Ann Danoff, Frederick Feit, James Slater, Michael J Attubato, Steven P Sedlis
Journal: Circulation (2012)

Background: Peri-procedural hyperglycemia is independently associated with mortality in patients undergoing PCI, but the mechanism is unknown. We aim to explore the association between diabetes, pe...
Abstract P189: Women with Gestational Diabetes Informed, but not Convinced of Power to Prevent CVD
Authors: Karen E Remsberg
Journal: Circulation (2012)

Introduction: Women with a history of gestational diabetes (hGDM) are more prone to develop overt type 2 diabetes and possibly CVD at a younger age than their peers with no history of GDM (non-hGDM). It is less clear how often these women are being screened and taking preventive action against developing these conditions. Hypothesis: We examined the hypothesis that women with hGDM are more knowledgeable than their non-hGDM controls regarding the risks that GDM poses for long-term development of type 2 diabetes and CVD. Methods: The Maternal Health Survey was piloted in a population sample (146 singleton live births; 73 hGDM and 73 non-hGDM) drawn from the 2008 Ohio birth records file (Vital Statistics, Ohio Department of Health). Health histories, health providers’ advice, and mothers’ health knowledge regarding screening and risks for diabetes and CVD were ascertained. To compare hGDM and non-hGDM, descriptive statistics, adjusted odds ratios, and chi-squared statistics were performed. Results: hGDM cases were more likely than controls to report a family history of gestational diabetes [OR= 1.60 (95% CI: 1.12, 2.90)], type 2 diabetes [OR= 1.71 (95% CI: 1.18, 2.49)], hypertension [OR= 2.00 (95% CI: 1.04, 3.87)], and polycystic ovary syndrome [OR= 2.28 (95% CI: 1.57, 3.29)]. hGDM cases were more likely to be encouraged to attend a postpartum visit [OR= 2.50 (95% CI: 1.05, 5.98)], told they were at risk for diabetes [OR= 56.20 (95% CI: 7.40, 426.57)] though not significantly more for CVD [OR= 2.60 (95% CI: 0.96, 7.34)], and how to avoid diabetes and CVD [OR=2.34 (95% CI: 1.40, 3.89)]. In addition, hGDM believed that they were more likely to develop diabetes than their peers (p = 0.002), equally likely to develop CVD (p = 0.211), and less able to change this situation (p = 0.036). Discussion: In conclusion, hGDM reported family histories that were positive for cardiometabolic diseases. Women with hGDM were better informed than the controls regarding their increased risk for diabetes, CVD, and their personal abilities to intervene, but not as confident in the value of prevention measures.
Hypoxia effect on non-malignant prostatic urethra during prostatectomy
Authors: J. W. Josephson, M. Vira, J. W. Gillespie, P. A. Pinto, R. Srinivasan, R. F. Chuaqui, M. R. Emmert-Buck, H. S. Erickson, J. A. Coleman
Journal: Journal of Clinical Oncology (2006)

20048 Background: With changes in technology and surgical technique paving the way to improved prostectomies, attention must be paid to the effects of hypoxia during variable surgical times. Hypoxia has been reported to play various roles that are implicated in the development of spurious molecular mutagenesis and tumorogenesis. However, the specifics leading to alterations and downstream effects in non-malignant tissues are unknown. Further, the consequence of hypoxia on tissues for analysis of tumor markers may be confounded. The objective of our study is to evaluate the effects of iatrogenic ischemia on surrounding non-malignant tissue in patients undergoing prostatectomy. As potential tissue markers to assess putative hypoxia tissue damage, gene expression levels in microdissected cell populations were evaluated. Methods: Normal prostatic urethra tissue was procured from five patients with laparoscopic 5 mm biopsy forceps at three time points during surgery and was immediately imbedded in OCT and placed on dry ice. First biopsy was taken prior to loss of blood supply after anterior bladder neck dissection. Second biopsy was taken directly after prostate was isolated from the patient. Third biopsy was taken ex vivo after vesico-urethral anastomosis. Urethral epithelium samples were normalized using the gold standard cell counting (2,000 microdissected cells) and quantitation of total RNA was conducted using NanoDrop technique. Gene expression analysis was assessed using quantitative RT-PCR (qRT-PCR) of four historically high and low abundant housekeeping genes (18s, ACTB, CYPA, and TFRC). Results: Housekeeping genes were up-regulated with an average four fold increase in transcript RNA at each time point respectively. Conclusion: These data suggest that hypoxia plays a putative significant role in the expression of genes in non-malignant tissues. The additional gene sets for analysis include traditional hypoxia related genes (e.g. HIF-1a, VEGF, AKT, and VHL) and non-hypoxia related genes (e.g. LAMP2, MTR, and STAT5B) to further investigate the prospective global up-regulation of gene expression. The conclusions may elucidate the role of hypoxia in disease processes and potentially its role in confounding or influencing tumor marker gene expression between patient samples. [Table: see text]
Teniposide and cisplatin given by intraperitoneal administration: Preclinical and phase I/pharmacokinetic studies
Authors: E. Chatelut, M. de Forni, P. Canal, C. Chevreau, H. Roche, Y. Plusquellec, N.P. Johnson, G. Houin, R. Bugat
Journal: Annals of Oncology (1991)
Association between treatment effects on disease progression (DP) endpoints and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC)
Authors: T. E. Delea, A. Khuu, A. Kay, J. Zheng, J. F. Baladi
Journal: Journal of Clinical Oncology (2009)

5105 Background: Access to safe and effective novel therapies may be expedited if DP endpoints (progression-free survival [PFS], time to progression [TTP], or event-free survival) are established as valid surrogates for OS in pivotal studies in mRCC. While the association between DP endpoints and OS has been established in other cancers, it has not been rigorously examined in patients with mRCC. We assessed the association between treatment effects on DP endpoints and treatment effects on OS in controlled trials of patients with mRCC. Methods: A systematic literature search was conducted (Medline, conference abstracts, references of retrieved studies/ reviews) to identify studies meeting the following criteria: controlled trials in mRCC of IL-2, IFN-α, sunitinib, sorafenib, pazopanib, bevacizumab, temsirolimus, or everolimus; English language; publication date≥1997; median time to DP and OS reported for 2 or more treatment groups. For each treatment group comparison, we calculated the differences in median time to DP and median OS and analyzed the association between the differences in median time to DP and differences in median OS using weighted ordinary least-squares (OLS) regression. Results: A total of 21 studies representing 6182 patients, 52 treatment groups, and 35 comparisons were identified. The median difference between treatment groups in time to DP averaged 1.3 months; the median difference between treatment groups in OS averaged 2.8 months. The correlation between differences in median time to DP and differences in median OS was 0.69 (p &lt; 0.0001). In weighted OLS regression, a 1 month difference in DP was associated with a 1.4 month difference in OS (p &lt; 0.0001, adjusted R-sq = 0.46). Conclusions: In patients receiving treatment for mRCC, treatment effects on DP endpoints are predictive of treatment effects on OS. [Table: see text]
Nephrology core curriculum. The American Society of Nephrology and the American Society of Nephrology Training Program Directors Committee.
Authors: R Kumar, R Alpern, T Berl, R Blantz, R Chevalier, T Hostetter, N Madias, D Salant, R Wiggins, W Bennett, A Chapman, G Ekonyan, R Falk, F J Gennari, J H Helderman, K Hruska, A Levey, M Lindheimer, R Miller, A Nissenson, S Schwab, T Schwab, R Schwartz, C Wilcox
Journal: Journal of the American Society of Nephrology (1997)

Kumar, R; Alpern, R; Berl, T; Blantz, R; Chevalier, R; Hostetter, T; Madias, N; Salant, D; Wiggins, R; Bennett, W; Chapman, A; Ekonyan, G; Falk, R; Gennari, F J; Helderman, J H; Hruska, K; Levey, A; Lindheimer, M; Miller, R; Nissenson, A; Schwab, S; Schwab, T; Schwartz, R; Wilcox, C
SMP-105, cell-wall skeleton purified from Mycobacterium bovis BCG Tokyo 172, activates innate immunity through TLR2/MyD88 pathway and prevents tumor metastasis into draining lymph nodes
Authors: Masashi Murata, Toshiyuki Sato, Masanori Miyauchi, Erina Koga, Mikio Aoki, Toru Kimura, Yasuo Kashiwazaki
Journal: Cancer Research (2007)

3554  [Background] Mycobacterium cell walls have diverse adjuvant activity, and in particular, the cell wall skeleton (CWS) of Mycobacterium bovis BCG has been expected as a medicinal product for tumor immunotherapy. The anti-tumor activity of CWS has been investigated using animal models for many years, but in these studies CWS was administered directly into the tumor or admixed with the tumor. Therefore, we cannot estimate the potent activity of CWS correctly because of the influence of local inflammation during administration. Also, the activation mechanism of innate immunity by CWS was controversial because immune responses were affected by the species or strains of CWS and its purity.  [Purpose] We optimized a method for preparing CWS from BCG Tokyo 172 strain (SMP-105), analyzed the activity of SMP-105 for macrophages and determined which TLRs participated in its recognition. We established a proper tumor model not affected by local inflammation at injected sites, and investigated the anti-tumor activity of SMP-105. Also, we compared the activity of SMP-105 with live BCG, which is widely used in superficial bladder carcinoma, in order to estimate the potential of SMP-105.  [Methods] SMP-105 was prepared from M. bovis BCG Tokyo 172 strain. Activity for the production of cytokines from macrophages was measured using a mouse macrophage cell line RAW264.7. Toll-like receptors for SMP-105 were investigated with a reporter-gene assay, TLR-knocked-down RAW264.7 cells, and macrophages prepared from TLR-KO mice. The anti-tumor activity of SMP-105 and live BCG was evaluated with a lymph node metastasis model using strain 2 guinea pigs bearing line 10 hepatoma.  [Results] SMP-105 induced TNF-α in a dose-dependent manner, while live BCG induced TNF-α in lower concentrations than SMP-105. The activation of NF-κB was dependent on TLR2 but not TLR4. The dependency on TLR2 was confirmed using TLR-knocked-down macrophages and TLR-KO macrophages. Weekly administration of 60 μg of SMP-105 and live BCG at a separate site from the implanted tumor suppressed tumor metastasis in draining lymph nodes.  [Conclusion] SMP-105 activated macrophages through the TLR2/MyD88 pathway, and SMP-105 showed comparative anti-tumor activity to live BCG. SMP-105 is a promising immunotherapeutic drug.