tbuckley/cabot-search huggingface dataset:
Relationship between lymphopenia and objective response rate with programmed death-1 (PD-1) inhibitor therapy: A single-center retrospective analysis.
Authors: Mark Yarchoan, Adam Diehl, Burles Avner Johnson, Blake Scott, Alexander Hopkins, Nilofer Saba Azad, Elizabeth M. Jaffee, Stuart A. Grossman
Journal: Journal of Clinical Oncology (2017)

e14512 Background: Lymphopenia is frequent in advanced cancers, but the impact of absolute lymphocyte count (ALC) on clinical responses with PD-1 immune checkpoint inhibitors is unknown. Methods: We performed a retrospective chart review of adult solid tumor patients treated with a PD-1 inhibitor (nivolumab or pembrolizumab) at Johns Hopkins from 2015-2016. Patients receiving PD-1 inhibitors concurrently with investigational immunotherapies, on unreported clinical trials or for cancers in which the activity of immune checkpoint inhibitors is unclear, or for whom response information is not available, were excluded. Data were collected on patient treatment history, objective response to PD-1 therapy by RECIST 1.1, and ALC at treatment initiation and one and three months after treatment initiation. Results: 172 patients met the inclusion criteria (lung n = 54; melanoma n = 61; kidney n = 25; other tumors n = 32). Lymphopenia (ALC &lt; 1000) was present in 30.2%, 26.7%, and 34.3%, at 0, 1, and 3 months after treatment initiation. In a multiple regression analysis that adjusted for age, sex, ethnicity, tumor type, number of prior therapies, and concurrent ipilimumab usage, lymphopenia at baseline was not predictive of response to an immune checkpoint inhibitor. However, in this same model, lymphopenia at 1 and 3 months after treatment initiation was inversely related to response rate (p &lt; 0.01). Of patients with lymphopenia at baseline, 37 patients (71.2%) had persistent lymphopenia (ALC &lt; 1000 at baseline persisting to month 3) whereas 15 patients (28.8%) had normalized lymphocyte counts by month 3. In a univariate analysis, patients with persistent lymphopenia had decreased response rates as compared to patients who were not lymphopenic at baseline (21.6% vs. 47.5%, p &lt; 0.01). However, patients with lymphopenia at baseline who had normalized lymphocyte counts at month 3 responded similarly as patients who were not lymphopenic at baseline (46.7% vs. 47.5%). Conclusions: Patients on anti–PD-1 therapy with persistent lymphopenia may have a reduced likelihood of responding to these agents. This association requires further validation in additional patient cohorts.
ACC/AHA/AACVPR/AAFP/ANA Concepts for Clinician–Patient Shared Accountability in Performance Measures
Authors: Eric D. Peterson, P. Michael Ho, Mary Barton, Craig Beam, L. Hayley Burgess, Donald E. Casey, Joseph P. Drozda, Gregg C. Fonarow, David Goff, Kathleen L. Grady, Dana E. King, Marjorie L. King, Frederick A. Masoudi, David R. Nielsen, Stephen Stanko
Journal: Circulation (2014)
Residual disease detection using targeted parallel sequencing predicts relapse in cytogenetically normal acute myeloid leukemia
Authors: Lukas Gaksch, Karl Kashofer, Ellen Heitzer, Franz Quehenberger, Shruti Daga, Sybille Hofer, Iris Halbwedl, Ricarda Graf, Nina Krisper, Gerald Hoefler, Armin Zebisch, Heinz Sill, Albert Wölfler
Journal: American Journal of Hematology (2017)

Despite achieving complete remission after intensive therapy, most patients with cytogenetically normal (CN) AML relapse due to the persistence of submicroscopic residual disease. In this pilot study, we hypothesized that detection of leukemia-specific mutations following consolidation treatment using a targeted parallel sequencing approach predicts relapse. We included 34 AML patients of whom diagnostic material and remission bone marrow slides after at least one cycle of consolidation were available. Isolated DNA was screened for mutations in 19 genes using an Ion Torrent sequencing platform. Furthermore, the variant allelic frequency of distinct mutations was validated by digital PCR and sequencing using a barcoding approach. Twenty-seven out of 34 patients could be analyzed for mutation clearance. We identified 68 somatic mutations at diagnosis (median, 3 mutations per patient; range 1-5) and 22 of these were still detected in 16 patients after consolidation therapy with a reliable sensitivity of 0.5% (median, 1 mutation; range 0-3). The most frequent noncleared mutations were found in DNMT3A. However, as persistence of these mutations has recently been shown to be without any impact on relapse risk, we performed survival and relapse risk analysis excluding DNMT3A mutations. Importantly, persistence of non-DNMT3A mutations was associated with a higher risk of AML relapse (7/8 pts versus 6/19 pts; P = .013) and with a shorter relapse-free survival (333 days vs. not reached; log-rank P = .0219). Detection of residual disease by routine targeted parallel sequencing proved feasible and effective as persistence of somatic mutations other than DNMT3A were prognostic for relapse in CN AML.
Differential modulation of oxidative stress in normal and cancer cells by mangafodipir improves the therapeutic index of anticancer drugs
Authors: Jérôme Alexandre, Carole Nicco, Christiane Chéreau, Alexis Laurent, François Goldwasser, Bernard Weill, Frédéric Batteux
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4930 

Intracellular H2O2 accumulation is a determining event for the cytotoxicity of anticancer agents independently of their molecular targets. Compounds that increase H2O2 levels enhance both the efficacy and toxicity of anticancer agents. Mangafodipir, a contrast agent for magnetic resonance imaging, increases both H2O2 synthesis through superoxide dismutase activity and H2O2 catabolism through catalase and glutathione-reductase activities. Therefore, we explored the ability of mangafodipir to modulate paclitaxel (PCX), 5FU and oxaliplatin (OXA) cytotoxicity in cancer and normal cells. Human leucocytes were exposed to either PCX, OXA or 5FU for 24h at IC50. Concomitant exposure to 400 μM mangafopidir decreased PCX, OXA and 5FU cytotoxicity by 50, 30 and 15%, respectively, as evaluated by MTT assay. The protective effect of mangafodipir on the hematologic toxicity of PCX was studied in BALB/c mice. Severe neutropenia and bone marrow hypoplasia observed in all animals at day 10 of PCX treatment (20 mg/kg ip x3/w) were abrogated by concomitant treatment with mangafodipir (10 mg/kg ip x3/w). Sublethal intraperitoneal administration of pathogen Staphyloccus aureus induced the early death of 14/17 mice with PCX-induced neutropenia and of 3/17 mangafodipir + PCX-treated mice. In contrast, mangafodipir enhanced the efficacy of anticancer agents in cancer cells, both in vitro and in vivo . Indeed, in CT26 mouse colon cancer cells, mangafodipir increased the cytotoxicity of PCX, OXA and 5FU by 5, 40 and 6%, respectively. Similar results were observed using Hepa1.6 mouse hepatoma and A549 human lung cancer cells. In mice with implanted syngenics CT26 cells, mangafodipir, PCX or their combination induced 40, 40 and 55% tumor reduction, respectively. To determine whether the differential effect of mangafodpir in normal and cancer cells was related to oxidative stress modulation, intracellular H2O2 levels were monitored in vitro by oxidation of the fluorescent probe H2DCFDA. Co-exposure of mangafodipir resulted in a 10 to 30% reduction of H2O2 accumulation induced by anticancer agents in leucocytes, but in a 4-fold increase in CT26 cells. Hence, mangafodipir protects against the toxicity of anticancer agents in normal cells, and increases their efficacy in cancer cells, both in vitro and in vivo . The resulting increased therapeutic index seems related to a differential modulation of H2O2 levels in normal and cancer cells and will be explored in an ongoing clinical trial.
2017 AHA/ACC Clinical Performance and Quality Measures for Adults With ST-Elevation and Non–ST-Elevation Myocardial Infarction
Authors: Hani Jneid, Daniel Addison, Deepak L. Bhatt, Gregg C. Fonarow, Sana Gokak, Kathleen L. Grady, Lee A. Green, Paul A. Heidenreich, P. Michael Ho, Corrine Y. Jurgens, Marjorie L. King, Dharam J. Kumbhani, Samir Pancholy
Journal: Journal of the American College of Cardiology (2017)
Effect of Intensity on Tumor Induction by Ultraviolet Radiation
Authors: Harold F. Blum
Journal: JNCI Journal of the National Cancer Institute (1943)

Journal Article Effect of Intensity on Tumor Induction by Ultraviolet Radiation Get access Harold F. Blum Harold F. Blum senior pharmacologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 5, June 1943, Pages 539–543, https://doi.org/10.1093/jnci/3.5.539 Published: 01 June 1943
Mental health among Iranian combat veterans with ankle-foot neuromusculoskeletal injuries
Authors: Arsia Taghva, Mostafa Allami, Kamyab Alizadeh, Anahita Zandi, Elahe Faraji, Zohreh Ganjparvar
Journal: Military Medical Research (2017)

Veterans with purely physical disorders, such as ankle-foot neuromusculoskeletal disorders, are often neglected in psychological assessments because mental health evaluations are usually focused on those with a psychological disturbance or with a high percentage of injury. The purpose of this study was to evaluate the psychological condition of veterans with ankle-foot neuromusculoskeletal disorders.A cross-sectional study was performed between 2014 and 2016 on veterans with war-related ankle-foot injuries living in two provinces of Iran. An information form for demographic data and injury-related factors was used. Additionally, the previously validated Persian version of the Symptom Checklist-90-Revision (SCL-90-R) questionnaire was used for data collection.The respondents were 215 male veterans with a mean age of 51.7 ± 7.5 years. The most common mental health problems were observed for the somatization (24.7%), obsessions-compulsions (14.4%), and anxiety (12.6%). Based on the Global Severity Index (GSI), 48.6% of individuals had a possible psychiatric/psychological illness. According to the multivariate regression analysis, GSI scores were significantly higher among veterans who were older than 27 years at the time of injury (P = 0.005), had an associated injury (P = 0.002), and had a history of hospitalization within the past 12 months for reasons other than their injury (P = 0.035).Approximately half of the combat veterans with ankle-foot neuromusculoskeletal disorders likely had psychological problems. The evaluation of the patterns and predicting factors of psychological conditions may inform strategic planning efforts and decision-making, which, in turn, may provide a better quality of life for veterans. Further studies that utilize longitudinal designs are needed to evaluate and compare the psychological status of different groups of veterans and other groups in the general population.
Abstract #183: SirT1 contributes to tumorigenicity and radioresistance in glioblastoma CD133+cells
Authors: Chiou Shih-Hwa, Yi-Wei Chen
Journal: Cancer Research (2009)

CD133-positive cells (CD133+) in glioma present the crucial role in the tumor grading, tumorigenicity, and radioresistance. However, the gene regulation mechanisms in maintaining the self-renewal and drug-resistant properties in cancer stem cells (CSC) of glioma are still unclear. SIRT1, is a NAD+ dependent histone deacetylase, regulates the lifespan and aging effect. Some studies revealed the relationship between the tumor control, anti-apoptosis, and anti-angiogenesis by inhibition of SIRT1. In this study, we detected the high expression levels of SirT1 in glioblastoma-derived CD133-positive cells (GBM-CD133+) as compared to GBM-CD133-. We further found knockdown the expression levels of SirT1 can inhibit the drug-resistant genes, and further partially block the self-renewal and tumor restoration abilities in GBM-CD133+. The apoptotic activities of annexin V, caspase 3, and PARP were effectively induced in GBM-CD133+ treated by SirT1 siRNA and further increase radioresenitivity and temozolomide-treated effects. In addition, knock-down of SirT1 could inhibit the expression of CD133 antigen, and further decrease tumorigenic capability in orthotopic-xenotransplanted SCID mice measured by living MRI and GFP imaging. The survival studies in mice confirm that the treatment effect of chemoradiotherapy for CD133+ can be improved by the treatment of SirT1 siRNA. In sum, this result supported that SirT1 participated antiproliferation, apoptotic ability, and radiosensitizing effects in GBM-CD133+. The overexpression of Sirt1 protein in GBM-CD133+ might be a new target for GBM therapy in the future.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 183.
CHAPTER XII: Interrelationships of Pulmonary Angiograms, Lung Scans, Hemodynamic Measurements, and Fibrinolytic Findings
Journal: Circulation (1973)

Data from pulmonary angiograms, lung scans, hemodynamic measurements, and tests of fibrinolysis were compared and correlated. In general, there was good correlation of the preinfusion scan perfusion defect with the overall angiographic severity, judged both subjectively and objectively. The highest correlation was obtained when only perfusion defects estimated by the two methods were compared. The correlation was lower when 24-hour changes estimated by scanning and angiography were compared. There was a tendency for the angiogram to reflect greater change. Hemodynamic abnormalities did not correlate well with the extent of preinfusion involvement judged by scanning or angiography, although in the urokinase patients there was a correlation of the fall in pulmonary arterial mean pressure with scanning or angiographic improvement. This correlation was not present in the patients treated only with heparin. There was no correlation of degree of fibrinolysis with resolution of emboli as estimated by lung scanning or angiography. This was true in all patients who received urokinase, regardless of initial clot size or degree of change after urokinase infusion.
SAMHSA Releases New State-By-State Reports on US Behavioral Health
Authors: Jeff Lyon
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Illusions regarding<i>Helicobacter pylori</i>clinical trials and treatment guidelines
Authors: David Y Graham
Journal: Gut (2017)

Identification of reliable Helicobacter pylori eradication therapy has proved difficult, in part because brief exposure of H. pylori to commonly used antimicrobials such as macrolides, nitroimidazoles or quinolones often results in resistance (bystander effect). Most treatment studies and meta-analyses contains major flaws preventing generalisability that making reliable treatment recommendations and guidelines an illusion (box 1).Box 1 
### Helicobacter pylori treatment illusions

Development of H. pylori therapy differs from other infectious diseases. Since the advent of antibiotics, infectious diseases therapy has been susceptibility based, whereas most H. pylori treatment guidelines recommend susceptibility testing only after two empiric therapy failures. Increased penicillin resistance in the 1970s prompted rapid changes in recommendations and the development of antimicrobial surveillance programme to regularly update recommendations thus allowing empirical therapies to remain effective.1 Despite increasing resistance, H. pylori treatment guidelines have continued to recommend increasingly ineffective therapies and most new empiric therapies consist of variations using those same drugs (eg, sequential therapy). Treatment success has focused on comparisons between regimens irrespective of cure rates and without consideration of the antibiotic susceptibility profile of the infection, thus producing illusions of success. For example, sequential therapy consists of 5 days of dual proton pump inhibitor (PPI)–amoxicillin therapy followed by 5 days of PPI–clarithromycin and metronidazole triple therapy (Bazzoli’s triple therapy).2 Interestingly, sequential therapy …
Development of the combined positive score (CPS) for the evaluation of PD-L1 in solid tumors with the immunohistochemistry assay PD-L1 IHC 22C3 pharmDx.
Authors: Karina Kulangara, Debra Ann Hanks, Stephanie Waldroup, Lindsay Peltz, Supriya Shah, Charlotte Roach, Jonathan Wes Juco, Kenneth Emancipator, Dave Stanforth
Journal: Journal of Clinical Oncology (2017)

e14589 Background: Developing clinically relevant and highly reproducible scoring methods for PD-L1 to identify patients who will respond effectively to anti-PD-1 therapy is key in the development of companion or complementary diagnostic assays. Methods: Scoring method for PD-L1 IHC 22C3 pharmDx in NSCLC have only captured the percentage on stained tumor cells using the tumor proportion score (TPS) (Roach et al. 2016, Appl Immunohistochem Mol Morphol.) (Garon et al. 2015, N Engl J Med.). In the KN012 study 2 out of 11 responders to pembrolizumab were detected with the TPS for the gastric indication. More and more additional data indicate that in some tumor indications PD-L1 staining on both tumor and tumor-associated immune cells is associated with clinical outcome. Therefore a method evaluating both tumor and immune cells in one sitting using the combined positive score was evaluated. Results: Scoring the same patient specimens with the new combined positive score method resulted in the detection of 9 out of 11 responders. Our internal inter- and intra- observer data shows that the CPS can be scored reproducibly with an overall agreement point estimates of 93% for intra-observer and an overall agreement of 87.6% for inter-observer reproducibility in gastric carcinoma. Additionally, CPS builds on the scoring method for NSCLC as it shares the same denominator, namely total number of tumor cells. CPS is evaluated based on the number of PD-L1 positive cells (tumor, lymphocytes and macrophages) in relation to total tumor cells, and hence allows the capture of tumor and immune cells in a single read. Conclusions: Our data demonstrates that the CPS scoring method is reproducible when scored by pathologists and clinically relevant for a number of indications.
Ovarian cancer with peritoneal carcinomatosis: Comparing of photodynamic treatment and HIPEC.
Authors: Alexey Privalov, Andrey Vazenin, Ludmila Chernova, Alexey Taratonov, Tatiana Gubaydulina
Journal: Journal of Clinical Oncology (2017)

e17040 Background: Peritoneal carcinomatosis is a very common by ovarian cancer (OC). Usual treatment`s approaches such as systemic drugs are not very effective. 5-year survival by OC depends of stage and are 15-20% in III stage and only 5% in IV stage. Most part of this patients die with progression of peritoneal disease. Standart treatment`s approach by OC is radical surgery with adjuvant chemotherapy. But in many cases this tactic can`t control peritoneal lesions and, therefore, outcomes. Methods: In our oncology center we are performing retrospective non-randomized prospective study comparing two different treatment options by ovarian`s peritoneal carcinomatosis - photodynamic therapy (PDT) and hyperthermic intraperitoneal chemotherapy (HIPEC). There were 25 patients in PDT-group and 21 patients in HIPEC-group. Treatment in PDT-group included 2-4 cycles of neo-adjuvant chemotherapy (cyclophosphamid+cisplatinum /CP/, n=7 or paclitaxel+cisplatinum /TC/, n=18 ), after which we performed surgery+PDT and then 4-6 cycles same chemotherapy. We used iv. photolon (Russia) as photosensitizer and 630-680 nm diod laser. Time of procedure was 20 minutes. Peritoneal Carcinomatosis Index (PCI) was 4,2 an averege (1-12). Treatment in HIPEC-group included 2-4 cycles of neo-adjuvant chemotherapy (cyclophosphamid+cisplatinum /CP/, n=21), after which we performed surgery+HIPEC and then 4-6 cycles the same chemotherapy. Medium PCI was 5,6 (2-11). We used “closed” HIPEC technique, with 3 inflow and 3 outflow catheters, Performer HT device by RanD and 7 liters of saline solution with 200 mg cisplatunum or 100 mg/m 2 taxans were used. Results: There were 11 recurrence in PDT-group (44%) and 10 recurrence in HIPEC-group (38%), t=1,06. Median of time to progression was 11.6 months in PDT-group and 13,5 months in HIPEC-group. Median of overall surviving was 18,4 and 24,1 months respectively. Conclusions: Using of PDT by ovarian cancer with peritoneal carcinomatosis didn`t show increasing of overall survival. We can also notice the non-statistical tendency of increasing time to progression in HIPEC-group. We run our study further and hope to collect more data for analysis.
Quality of Care and Satisfaction Among Patients Isolated for Infection Control
Authors: Jean-Jacques Parienti
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal