tbuckley/cabot-search huggingface dataset:
Trajectories of Stress, Depressive Symptoms, and Immunity in Cancer Survivors: Diagnosis to 5 Years
Authors: Barbara L. Andersen, Neha Godiwala Goyal, Travis D. Westbrook, Brenden Bishop, William E. Carson
Journal: Clinical Cancer Research (2016)

Five-year disease endpoint trajectories are available for every cancer site. In contrast, there are few longitudinal, biobehavioral studies of survivors extending beyond the first or second year following diagnosis. This gap is addressed with stress, depressive symptom, and immunity data from breast cancer patients followed continuously for 5 years.Women (N = 113) diagnosed and surgically treated for breast cancer and awaiting adjuvant therapy completed self-report measures of stress and depressive symptoms and provided blood for immune assays [natural killer cell cytotoxicity (NKCC) and T-cell blastogenesis]. Assessments (N = 12) were repeated every 4 to 6 months for 5 years.Multiphase linear mixed models show phases of change and identified specific time points of change. Cancer stress shows two distinct phases of decline, with the change point being 12 months. In contrast, a steep decline in depressive symptoms occurs by 7 months, with stable, low levels thereafter. NKCC shows a steady upward trajectory through 18 months and upper limit stability thereafter, whereas there was no reliable trajectory for T-cell blastogenesis.For the first time, trajectories and specific time points of change in biobehavioral data for breast cancer survivors are provided, traced through 5 years. Following diagnosis, the breast survivor experience is one of a co-occurrence of change (recovery) in psychologic and innate immunity markers from diagnosis to18 months, and a pattern of stability (depression, NKCC) or continued improvement (stress) through year 5. These data provide new directions for survivorship care and detail of the biobehavioral trajectory. Clin Cancer Res; 23(1); 52-61. ©2016 AACR.
Association of <i>isocitrate dehydorgenase-1</i> (<i>IDH-1</i>) mutations with elevated oncometabolite 2-hydroxyglutarate (2HG) in advanced colorectal cancer.
Authors: Nazanin Fallah-Rad, Philippe L. Bedard, Lillian L. Siu, Suzanne Kamel-Reid, Helen Chow, Zhang Weijiang, Raymond Jang, Monika K. Krzyzanowska, Albiruni R. A. Razak, Eric Xueyu Chen
Journal: Journal of Clinical Oncology (2016)

627 Background: IDH-1 mutations are common in AML, gliomas, and intrahepatic cholangiocarcinoma. The enzyme product of the IDH-1 R132 variant preferentially catalyzes the NADPH-dependent reduction of alpha-ketoglutarate to the oncometabolite R-2-Hydroxyglutarate (R-2HG), resulting in accumulation of R-2HG, relative to its enantiomer, S-2HG. Elevated plasma levels of 2HG and/or higher ratios of R/S have been observed in AML and intrahepatic cholangiocarinoma, but not in gliomas. Only a few cases of IDH-1/2 mutations have been reported in advanced colorectal cancers (CRC). We investigated plasma levels of 2HG and relative ratios of R/S in CRC patients harboring IDH-1/2mutations. Methods: Between 2012 and 2015, 428 patients with advanced CRC were molecularly profiled through the COMPACT and IMPACT programs at the Princess Margaret Cancer Centre. Tumor DNAs were isolated from FFPE archived samples and genotyped using a customized Sequenom panel or Illumina MiSeq TruSeq Amplicon Cancer Panel in a CLIA-certified laboratory. Plasma samples from patients harboring IDH-1/2mutations and 4 gender/age matched control patients were analyzed for 2HG, R-2HG and S-2HG using HPLC tandem mass spectrometry coupled with a CHIROBIOTIC R column. Results: Of 428 patients with advanced CRC, 4 (0.9%) patients were identified to harbor IDH-1 mutation. No IDH-2 mutations were detected. The variants identified were R132C (2 patients), R132S, and R132H. 3 of 4 patients also harbored KRAS mutations. Patients with IDH-1 mutations had higher levels of 2HG (319 ± 102 ng/ml vs 195 ± 43 ng/ml, p = 0.043). The ratio of R/S were 0.44, 0.75, 1.59, and 2.60 in 4 patients with IDH-1 mutations and 1.3, 0.90, 0.41 and 0.67 in 3 patients without IDH-1mutations. Conclusions: IDH-1 mutations are rare in advanced CRC. 3 of 4 patients in our study had concurrent KRAS mutations. Patients with IDH-1 mutations had higher levels of oncometabolite 2HG compared with controls with no difference in R/S ratio.
Neoplasms in Mice Inoculated with Cell-Free Extracts or Filtrates of Leukemic Mouse Tissues. II. Leukemia in Hybrid Mice Produced by Cell-Free Filtrates
Authors: Sarah E. Stewart
Journal: JNCI Journal of the National Cancer Institute (1955)

Journal Article Neoplasms in Mice Inoculated with Cell-Free Extracts or Filtrates of Leukemic Mouse Tissues. II. Leukemia in Hybrid Mice Produced by Cell-Free Filtrates Get access Sarah E. Stewart Sarah E. Stewart National Cancer Institute,2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 16, Issue 1, August 1955, Pages 41–53, https://doi.org/10.1093/jnci/16.1.41 Published: 01 August 1955 Article history Received: 10 December 1954 Published: 01 August 1955
Social adjustment of chronic dialysis patients
Authors: A K De-Nour
Journal: American Journal of Psychiatry (1982)

The author gathered information by questionnaire about the leisure activities of 102 patients receiving chronic hemodialysis. The patients reported a severe decrease in interest, especially in family and social leisure activities, and an even greater decrease in actual participation in leisure activities. The results indicate that hemodialysis patients do not suppress or deny the many problems they experience. The author hypothesizes that the paucity of information in this area is probably linked to the denial of the staff who treat these patients. The sharp decline in the leisure activities to the group studied suggests the need to devise methods of intervention to improve the quality of life of chronic dialysis patients.
CAR T Cell Therapy for Solid Tumors
Authors: Kheng Newick, Shaun O'Brien, Edmund Moon, Steven M. Albelda
Journal: Annual Review of Medicine (2016)

The field of cancer immunotherapy has been re-energized by the application of chimeric antigen receptor (CAR) T cell therapy in cancers. These CAR T cells are engineered to express synthetic receptors that redirect polyclonal T cells to surface antigens for subsequent tumor elimination. Many CARs are designed with elements that augment T cell persistence and activity. To date, CAR T cells have demonstrated tremendous success in eradicating hematologic malignancies (e.g., CD19 CARs in leukemias). However, this success has yet to be extrapolated to solid tumors, and the reasons for this are being actively investigated. We characterize some of the challenges that CAR T cells have to surmount in the solid tumor microenvironment and new approaches that are being considered to overcome these hurdles.
KEYNOTE-055: A phase II trial of single agent pembrolizumab in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who have failed platinum and cetuximab.
Authors: Steven Francis Powell, Stephen V. Liu, Ammar Sukari, Christine H. Chung, Joshua Bauml, Robert I. Haddad, Christine K. Gause, Michelle Niewood, Linda L. Gammage, Holly Brown, Amy Meister, Jonathan D. Cheng, Mark M. Gitau
Journal: Journal of Clinical Oncology (2015)

TPS3094 Background: Treatment options are limited for pts with recurrent and/or metastatic HNSCC whose disease has progressed after platinum and cetuximab therapy. Pembrolizumab (MK-3475) is a humanized IgG4 monoclonal antibody designed to block interaction between activated T-cell-specific programmed death receptor 1 (PD-1) and its ligands PD-L1 and PD-L2. Preclinical studies have shown that blocking PD-1/PD-L1 interaction promotes infiltration of activated tumor-specific effector T cells, leading to tumor cell death. In KEYNOTE-012, a phase 1b clinical study, pembrolizumab exhibited antitumor activity in patients with recurrent or metastatic, PD-L1–positive HNSCC. Treatment with intravenous pembrolizumab 10 mg/kg every 2 weeks resulted in an objective response rate (ORR) of 19.6% (confirmed and unconfirmed responses) by investigator review, and the magnitude of response was positively correlated with PD-L1 expression in the tumor tissue (P= 0.018). Methods: KEYNOTE-055 (NCT02255097) is a multicenter, open-label, nonrandomized phase 2 trial with the primary objective to evaluate the efficacy and safety of pembrolizumab in 150 pts with recurrent and/or metastatic HNSCC resistant to platinum and cetuximab. Pembrolizumab will be administered intravenously for up to 24 months at a dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity. Eligible pts must undergo a core or excisional biopsy prior to treatment for evaluation of PD-L1. The primary efficacy parameter is ORR, with response to treatment assessed every 6-9 weeks by central radiology review using RECIST v1.1. Secondary efficacy end points include: duration of response, ORR per modified RECIST v1.1 (to account for the unique tumor response profile of pembrolizumab), ORR for HPV+ pts, progression-free survival (PFS), and overall survival (OS). For the ORR analyses, a 97.5% confidence interval and 1-sided P value will be provided using exact binomial distribution. Kaplan-Meier statistics will assess PFS and OS. Adverse events (AEs) will be monitored and graded using CTCAE v4.0. Clinical trial information: NCT02255097.
Don't confuse with anticholinergic intoxication
Authors: R Howells
Journal: BMJ (1994)

there are few published data to support these claims.In a prospective randomised trial in 140 patients that compared laparoscopic and open appendicectomy Tate et al found no significant differences between the groups in pain score, analgesic requirement, hospital stay, or time to return to work.2The only significant finding was that the operating time was nearly twice as long in the laparoscopic group.In addition, conversion to an open operation was necessary in a fifth of the patients undergoing laparoscopy.Further prospective randomised trials are needed to establish the place of laparoscopic surgery.Without such data the current enthusiasm for laparoscopic surgery may be unfounded.
Spontaneous Adrenal Medullary Tumors in Hybrid Mice&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: E. Elizabeth Jones, L. Jeanne Woodward
Journal: JNCI Journal of the National Cancer Institute (1954)

Spontaneous Adrenal Medullary Tumors in Hybrid Mice Get access E. Elizabeth Jones, E. Elizabeth Jones Department of Zoology and Physiology, Wellesley College, Wellesley, Mass. Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Jeanne Woodward L. Jeanne Woodward Department of Zoology and Physiology, Wellesley College, Wellesley, Mass. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 449–461, https://doi.org/10.1093/jnci/15.3.449 Published: 01 December 1954 Article history Received: 16 August 1954 Published: 01 December 1954
Arbitrary thresholds of natural variability and severity should not be used to diagnose chronic obstructive pulmonary disease
Authors: Vito Brusasco, Riccardo Pellegrino, Martin R Miller
Journal: BMJ (2016)

We appreciate Conway and colleagues’ efforts to simplify the clinical approach to chronic obstructive pulmonary disease (COPD),1 but we think that this approach is not appropriate for the diagnosis of COPD in primary care. The authors suggest using the FEV1/FVC (forced expiratory volume in one second/forced vital capacity) ratio <0.70 to confirm the diagnosis of COPD,2 even though this has been hotly debated since it was first proposed by the GOLD (Global Initiative for Chronic …
Differentiation of Mature Eosinophils From Human Embryonic and Induced Pluripotent Stem Cells.
Authors: Wenyu Yang, Feng Ma, Kenji Matsumoto, Natsumi Nishihama, Hiroshi Sagara, Yasuhiro Ebihara, Yanzheng Gu, Hirohisa Saito, Xiaofan Zhu, Hiromitsu Nakauchi, Kohichiro Tsuji
Journal: Blood (2010)
CD69 controls the uptake of L-tryptophan through LAT1-CD98 and AhR-dependent secretion of IL-22 in psoriasis
Authors: Danay Cibrian, María Laura Saiz, Hortensia de la Fuente, Raquel Sánchez-Díaz, Olga Moreno-Gonzalo, Inmaculada Jorge, Alessia Ferrarini, Jesús Vázquez, Carmen Punzón, Manuel Fresno, Miguel Vicente-Manzanares, Esteban Daudén, Pedro M Fernández-Salguero, Pilar Martín, Francisco Sánchez-Madrid
Journal: Nature Immunology (2016)
P-066 New methods of detecting oxaliplatin-induced peripheral sensory neuropathy in patients undergoing adjuvant treatment with 5-fluorouracil and oxaliplatin for colon cancer
Authors: J. Szpejewska, C.D. Mørch, M. Yilmaz, L. Arendt-Nielsen, U. Falkmer
Journal: Annals of Oncology (2016)
Morpholino-mediated Knockdown of DUX4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics
Authors: Jennifer CJ Chen, Oliver D King, Yuanfan Zhang, Nicholas P Clayton, Carrie Spencer, Bruce M Wentworth, Charles P Emerson, Kathryn R Wagner
Journal: Molecular Therapy (2016)

Derepression of DUX4 in skeletal muscle has emerged as a likely cause of pathology in facioscapulohumeral muscular dystrophy (FSHD). Here we report on the use of antisense phosphorodiamidate morpholino oligonucleotides to suppress DUX4 expression and function in FSHD myotubes and xenografts. The most effective was phosphorodiamidate morpholino oligonucleotide FM10, which targets the polyadenylation signal of DUX4. FM10 had no significant cell toxicity, and RNA-seq analyses of FSHD and control myotubes revealed that FM10 down-regulated many transcriptional targets of DUX4, without overt off-target effects. Electroporation of FM10 into FSHD patient muscle xenografts in mice also down-regulated DUX4 and DUX4 targets. These findings demonstrate the potential of antisense phosphorodiamidate morpholino oligonucleotides as an FSHD therapeutic option.
Cytogenic Study of Embryonic Chick Pancreas. I. Exocrine Tissue
Authors: R F ZEIGEL
Journal: JNCI Journal of the National Cancer Institute (1962)

Chick-embryo exocrine pancreas was examined at various days of incubation with both the light and electron microscopes. Tissue prepared for electron microscopy was fixed in either Palade's or Dalton's fluids. Some ultrathin sections were stained with lead salts before examination. The development of the acinar cells as observed by electron microscopy is described with relation to temporal and spatial changes and compared with light microscopic observations. The young acinar cells are similar in many respects to the cuboidal duct cells with which they are closely associated. One of the earliest characteristics distinguishing the young acinar cells is the acquisition of a large nucleolus. The mitochondria, endoplasmic reticulum, zymogen granules, Golgi components, and lipide content exhibit a progressive and distinctive change during ontogenic development. Evidence from this and previous developmental studies indicates that production of increasing amounts of secretory material (zymogen) is concomitant with the observation of increased amounts of organized and closely spaced ergastoplasm in the acinar cells. A few small zymogen granules are present at 6 days of incubation, though the increase in secretion and hyperplasia of the cells and cell system at about 11 to 15 days of incubation follows the general pattern described for the chick embryo in other studies. Mature cyto-logical configurations are observed at approximately the time of hatching. Exocrine cell components, which do not change dramatically throughout development, are characterized. Among these are the microvilli, plasma membranes, and terminal bars.
Treatment with patiromer decreases aldosterone in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors
Authors: Matthew R. Weir, George L. Bakris, Coleman Gross, Martha R. Mayo, Dahlia Garza, Yuri Stasiv, Jinwei Yuan, Lance Berman, Gordon H. Williams
Journal: Kidney International (2016)

Elevated serum aldosterone can be vasculotoxic and facilitate cardiorenal damage. Renin-angiotensin system inhibitors reduce serum aldosterone levels and/or block its effects but can cause hyperkalemia. Patiromer, a nonabsorbed potassium binder, decreases serum potassium in patients with chronic kidney disease on renin-angiotensin system inhibitors. Here we examined the effect of patiromer treatment on serum aldosterone, blood pressure, and albuminuria in patients with chronic kidney disease on renin-angiotensin system inhibitors with hyperkalemia (serum potassium 5.1-6.5 mEq/l). We analyzed data from the phase 3 OPAL-HK study (4-week initial treatment phase of 243 patients; 8-week randomized withdrawal phase of 107 patients). In the treatment phase, the (mean ± standard error) serum potassium was decreased concordantly with the serum aldosterone (-1.99 ± 0.51 ng/dl), systolic/diastolic blood pressure (-5.64 ± 1.04 mm Hg/-3.84 ± 0.69 mm Hg), and albumin-to-creatinine ratio (-203.7 ± 54.7 mg/g), all in a statistically significant manner. The change in the plasma renin activity (-0.44 ± 0.63 μg/l/hr) was not significant. In the withdrawal phase, mean aldosterone levels were sustained with patiromer (+0.23 ± 1.07 ng/dl) and significantly increased with placebo (+2.78 ± 1.25 ng/dl). Patients on patiromer had significant reductions in mean systolic/diastolic blood pressure (-6.70 ± 1.59/-2.15 ± 1.06 mm Hg), whereas those on placebo did not (-1.21 ± 1.89 mm Hg/+1.72 ± 1.26 mm Hg). Significant changes in plasma renin activity were found only in the placebo group (-3.90 ± 1.41 μg/l/hr). Thus, patiromer reduced serum potassium and aldosterone levels independent of plasma renin activity in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.
Abstract MP62: Age and Gender Differences in Cardiovascular Health in a Rural Cohort of Children and Adults
Authors: Stephanie J Frisbee, Sheldon Steiner, Courtney Pilkerton, Sarah Singh, Adam Christian, Thomas K Bias
Journal: Circulation (2015)

BACKGROUND:  Cardiovascular disease is the leading cause of death in the U.S. and, despite advances in treatment modalities, the increasing prevalence of risk factors, particularly lifestyle-based risk factors, has led to a concern for future increased societal burden of cardiovascular disease. This has also highlighted the need for an emphasis on population approaches to the promotion and support of cardiovascular health. To this end, the American Heart Association recently developed a comprehensive cardiovascular health index (CVHI) incorporating behavioral and biological factors. OBJECTIVE: The objective of the current study was to assess CVHI in a large cohort of children and adults and assess how CVHI changes with increasing age and between genders. METHODS: We used data from the C8 Health Project to perform a secondary data analysis consisting of a final sample of 51,652 adults (≥20 years old) and 9624 children (
P-060 Endoscopic colorectal stenting for malignant large bowel obstruction comparing to surgery
Authors: D.H. Kang, H.W. Kim, C.W. Choi, S.B. Park, S.J. Kim, H.S. Nam, H.H. Jang, S.B. Lee, S.H. Lee, J.M. Park
Journal: Annals of Oncology (2016)
Why Physicians Hate “Patient Satisfaction”: The Real Reasons
Authors: P. Dileep Kumar
Journal: Annals of Internal Medicine (2016)

Letters5 July 2016Why Physicians Hate “Patient Satisfaction”: The Real ReasonsP. Dileep Kumar, MDP. Dileep Kumar, MDFrom East Michigan Hospitalists, Port Huron, Michigan.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0008 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Nash (1) is right about 1 thing: Patient and family experiences are important in the business of caring. This point is usually ignored in the intense science of providing medical care. Relying on patient satisfaction scores from surveys is not the answer to this malady. As it stands now, the cure is worse than the disease.Physicians' main objections to using patient satisfaction scores are not the themes mentioned in this article. Patient satisfaction does not correlate with quality of care in any randomized, controlled trials. If we insist on randomized trials and evidence-based data for every ...References1. Nash IS. Why physicians hate “patient satisfaction” but shouldn't. Ann Intern Med. 2015;163:792-3. [PMID: 26344665]. doi:10.7326/M15-1087 LinkGoogle Scholar2. Reponen E, Tuominen H, Hernesniemi J, Korja M. Patient satisfaction and short-term outcome in elective cranial neurosurgery. Neurosurgery. 2015;77:769-75. [PMID: 26244270] doi:10.1227/NEU.0000000000000931 CrossrefMedlineGoogle Scholar3. Healthgrades. Dr. Ira S. Nash, MD. Accessed at www.healthgrades.com/physician/dr-ira-nash-2nhjs on 11 December 2015. Google Scholar4. Briggs N. Edgemont resident Ira Nash honored by Press Ganey. Scarsdale Daily Voice. 18 November 2015. Accessed at http://scarsdale.dailyvoice.com/neighbors/edgemont-resident-ira-nash-honored-by-press-ganey/604793 on 27 November 2015. Google Scholar Author, Article, and Disclosure InformationAffiliations: From East Michigan Hospitalists, Port Huron, Michigan.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=L16-0008. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoWhy Physicians Hate “Patient Satisfaction” but Shouldn't Ira S. Nash Why Physicians Hate “Patient Satisfaction”: The Real Reasons Ira S. Nash Metrics 5 July 2016Volume 165, Issue 1Page: 71-72KeywordsConflicts of interestDisclosureEvidence based medicineHealth care qualityNeurosurgeryPatient advocacyPatientsRandomized trials ePublished: 5 July 2016 Issue Published: 5 July 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From the Children’s Oncology Group
Authors: Robert B. Gerbing, Todd A. Alonzo, Lillian Sung, Alan S. Gamis, Soheil Meshinchi, Sharon E. Plon, Alison A. Bertuch, Maria M. Gramatges
Journal: Journal of Clinical Oncology (2016)

Purpose Suboptimal outcomes for children with acute myeloid leukemia (AML) necessitate maximally intensive therapy. Consequently, serious adverse events, such as prolonged periods of profound myelosuppression, contribute to AML treatment-related mortality. Telomeres, the repetitive DNA-protein structures at chromosome ends, influence cellular replicative capacity in that critically short telomeres can induce cell senescence or apoptosis. Our objective was to evaluate the impact of telomere length on duration of post-therapy neutropenia in a pediatric AML cohort. Patients and Methods Patients were diagnosed with de novo AML, enrolled in Children's Oncology Group study AAML0531, and included those with (n = 53) and without (n = 62) significantly delayed neutrophil recovery after chemotherapy. We used quantitative polymerase chain reaction to measure telomere content (TC), a validated proxy for telomere length, from remission bone marrow samples obtained after the second induction chemotherapy course. Results Less TC was significantly associated with prolonged neutropenia after the fourth ( P < .001) and fifth chemotherapy courses ( P = .002). Cox regression adjusting for age at diagnosis confirmed that TC remained independently predictive of time to recovery of absolute neutrophil count for both the fourth and fifth courses ( P = .002 and .009, respectively). DNA from patients was analyzed for germline mutations in four telomere maintenance genes associated with telomere biology disorders. Sequence analysis revealed no enrichment of rare or novel variants in the delayed recovery group. Conclusion Our results suggest that TC at end of AML induction is associated with hematopoietic reconstitution capacity independently of age and may identify those at highest risk for markedly delayed bone marrow recovery after AML therapy.