tbuckley/cabot-search huggingface dataset:
Incidence of skeletal-related events (SREs) among prostate cancer patients.
Authors: Marianne Ulcickas Yood, Teresa Maria Zyczynski, Karen Wells, Deborah Casso, Benjamin Gutierrez, Kimberley J. Woodcroft, Shinta Cheng
Journal: Journal of Clinical Oncology (2013)

e16035 Background: Skeletal related events (SREs) occur in men with prostate cancer and may result from both bone metastases and exposure to androgen deprivation therapy (ADT). The objective of this study was to quantify the incidence of SREs in patients with prostate cancer treated with ADT or orchiectomy in clinical practice. Methods: Prostate cancer patients served by Henry Ford Health System (HFHS) were identified via the HFHS tumor registry. Eligible patients were newly diagnosed with prostate cancer between 2004 and 2010 and treated with ADT or orchiectomy. Comprehensive population-based data were compiled using tumor registry with linkages to pharmacy, laboratory results, and healthcare encounter databases. SREs included spinal cord compression, surgery to bone, pathologic fracture and radiation to bone. Disease progression and metastases were identified by medical record review. Results: We identified 702 patients with prostate cancer and receipt of ADT or orchiectomy; 57.6% were &gt;70 years of age and 43.7% were African American. 56.3% of patients were initially diagnosed at AJCC stage II, 9.8% at stage III, 22.1% at stage IV, and 11.8% had missing or unknown stage. A total of 93 patients (13.2%) had one or more SREs: radiation to bone (8.5%) and spinal cord compression (3.1%) were the most common SREs. We then limited the cohort to patients initially diagnosed with or progressing to AJCC stage IV prostate cancer (N=207). Among this group, 47.8% were &gt;70 years of age. The mean time from stage IV diagnosis to end of follow-up was 35.6 months. In this subgroup, 16.4% of patients were initially diagnosed at AJCC stage II, 8.2% at stage III, 69.6% at stage IV, and 5.8% had missing or unknown stage. 57 patients (27.5%) had one or more SREs. Conclusions: Some clinical trials have found 36-41% of high-risk metastatic prostate cancer patients developed SREs during 3 years of follow-up. In this population-based cohort of patients with prostate cancer receiving ADT or orchiectomy and treated in real-world clinical practice, we found the incidence of SREs to be lower than what has been reported in clinical trials. Additional analyses exploring the incidence of SREs in patients diagnosed with metastatic castrate resistant prostate cancer will be presented.
Recommended Guidelines for Monitoring, Reporting, and Conducting Research on Medical Emergency Team, Outreach, and Rapid Response Systems: An Utstein-Style Scientific Statement
Authors: Mary Ann Peberdy, Michelle Cretikos, Benjamin S. Abella, Michael DeVita, David Goldhill, Walter Kloeck, Steven L. Kronick, Laurie J. Morrison, Vinay M. Nadkarni, Graham Nichol, Jerry P. Nolan, Michael Parr, James Tibballs, Elise W. van der Jagt, Lis Young
Journal: Circulation (2007)

][19][20] Measurements of abnormal physiology, including temperature, pulse rate, blood pressure, respiratory rate, hemoglobin, oxygen saturation by pulse oximetry, and deterioration of mental status, are therefore important to any system designed for early detection of physiological instability.At a minimum, these measurements must be obtained accurately and recorded with appropriate frequency.A system that both recognizes significantly abnormal values and triggers an immediate and appropriate treatment response is required.The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel.Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.
Utility and tolerability of the long-pulsed 1064-nm neodymium:yttrium-aluminum-garnet (LP Nd:YAG) laser for treatment of symptomatic or disfiguring vascular malformations in children and adolescents
Authors: Aditi S. Murthy, Annelise Dawson, Deepti Gupta, Shanna Spring, Kelly M. Cordoro
Journal: Journal of the American Academy of Dermatology (2017)
Next-generation Sequencing of Nonmuscle Invasive Bladder Cancer Reveals Potential Biomarkers and Rational Therapeutic Targets
Authors: Eugene J. Pietzak, Aditya Bagrodia, Eugene K. Cha, Esther N. Drill, Gopa Iyer, Sumit Isharwal, Irina Ostrovnaya, Priscilla Baez, Qiang Li, Michael F. Berger, Ahmet Zehir, Nikolaus Schultz, Jonathan E. Rosenberg, Dean F. Bajorin, Guido Dalbagni, Hikmat Al-Ahmadie, David B. Solit, Bernard H. Bochner
Journal: European Urology (2017)
Do the American Society of Clinical Oncology Value Framework and the European Society of Medical Oncology Magnitude of Clinical Benefit Scale Measure the Same Construct of Clinical Benefit?
Authors: Sierra Cheng, Erica J. McDonald, Matthew C. Cheung, Vanessa S. Arciero, Mahin Qureshi, Di Jiang, Doreen Ezeife, Mona Sabharwal, Alexandra Chambers, Dolly Han, Natasha Leighl, Kelley-Anne Sabarre, Kelvin K.W. Chan
Journal: Journal of Clinical Oncology (2017)

Purpose Whether the ASCO Value Framework and the European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (MCBS) measure similar constructs of clinical benefit is unclear. It is also unclear how they relate to quality-adjusted life-years (QALYs) and funding recommendations in the United Kingdom and Canada. Methods Randomized clinical trials of oncology drug approvals by the US Food and Drug Administration, European Medicines Agency, and Health Canada between 2006 and August 2015 were identified and scored using the ASCO version 1 (v1) framework, ASCO version 2 (v2) framework, and ESMO-MCBS by at least two independent reviewers. Spearman correlation coefficients were calculated to assess construct (between frameworks) and criterion validity (against QALYs from the National Institute for Health and Care Excellence [NICE] and the pan-Canadian Oncology Drug Review [pCODR]). Associations between scores and NICE/pCODR recommendations were examined. Inter-rater reliability was assessed using intraclass correlation coefficients. Results From 109 included randomized clinical trials, 108 ASCOv1, 111 ASCOv2, and 83 ESMO scores were determined. Correlation coefficients for ASCOv1 versus ESMO, ASCOv2 versus ESMO, and ASCOv1 versus ASCOv2 were 0.36 (95% CI, 0.15 to 0.54), 0.17 (95% CI, −0.06 to 0.37), and 0.50 (95% CI, 0.35 to 0.63), respectively. Compared with NICE QALYs, correlation coefficients were 0.45 (ASCOv1), 0.53 (ASCOv2), and 0.46 (ESMO); with pCODR QALYs, coefficients were 0.19 (ASCOv1), 0.20 (ASCOv2), and 0.36 (ESMO). None of the frameworks were significantly associated with NICE/pCODR recommendations. Inter-rater reliability was good for all frameworks. Conclusion The weak-to-moderate correlations of the ASCO frameworks with the ESMO-MCBS, as well as their correlations with QALYs and with NICE/pCODR funding recommendations, suggest different constructs of clinical benefit measured. Construct convergent validity with the ESMO-MCBS did not increase with the updated ASCO framework.
Glutamine supplementation suppresses herpes simplex virus reactivation
Authors: Kening Wang, Yo Hoshino, Kennichi Dowdell, Marta Bosch-Marce, Timothy G. Myers, Mayra Sarmiento, Lesley Pesnicak, Philip R. Krause, Jeffrey I. Cohen
Journal: Journal of Clinical Investigation (2017)

Chronic viral infections are difficult to treat, and new approaches are needed, particularly those aimed at reducing reactivation by enhancing immune responses. Herpes simplex virus (HSV) establishes latency and reactivates frequently, and breakthrough reactivation can occur despite suppressive antiviral therapy. Virus-specific T cells are important to control HSV, and proliferation of activated T cells requires increased metabolism of glutamine. Here, we found that supplementation with oral glutamine reduced virus reactivation in latently HSV-1–infected mice and HSV-2–infected guinea pigs. Transcriptome analysis of trigeminal ganglia from latently HSV-1–infected, glutamine-treated WT mice showed upregulation of several IFN-γ–inducible genes. In contrast to WT mice, supplemental glutamine was ineffective in reducing the rate of HSV-1 reactivation in latently HSV-1–infected IFN-γ–KO mice. Mice treated with glutamine also had higher numbers of HSV-specific IFN-γ–producing CD8 T cells in latently infected ganglia. Thus, glutamine may enhance the IFN-γ–associated immune response and reduce the rate of reactivation of latent virus infection.
In vivo real-time imaging of tumor microcirculatory alterations in colorectal liver metastatic xenografts by chemotherapy using multiphoton microscopy.
Authors: Koji Tanaka, Masato Okigami, Yuji Toiyama, Yuhki Morimoto, Kohei Matsushita, Mikio Kawamura, Kiyoshi Hashimoto, Susumu Saigusa, Yoshinaga Okugawa, Junichiro Hiro, Yasuhiro Inoue, Keiichi Uchida, Toshimitsu Araki, Yasuhiko Mohri, Akira Mizoguchi, Masato Kusunoki
Journal: Journal of Clinical Oncology (2012)

e21053 Background: Tumor endothelium is a distinct target for anticancer treatments of metastatic colorectal cancer. Various chemotherapeutics themselves have anti-angiogenic effects on tumor microenvironment by targeting proliferative endothelial cells during tumor angiogenesis. In this study, we imaged the dynamics of tumor microcirculation of colorectal liver metastasis in living mice in vivo real-time using two-photon laser scanning microscopy (TPLSM), and evaluated the microcirculatory alterations in tumor microenvironment by chemotherapy. Methods: Red fluorescent protein expressing human colorectal cancer cell line (HT29) was inoculated to the spleen of green fluorescent protein expressing nude mice. 5-fluorouracil or irinotecan was administered three times a week for more than three weeks for metronomic scheduling. Intravital TPLSM was performed at multiple time points for time-series imaging of liver metastatic xenografts in the same mice. The alterations in tumor microcirculation during chemotherapy was evaluated by measuring blood flows at tumor vessels of colorectal liver metastasis and hepatic sinusoids of adjacent normal liver. Results: At the first TPLSM imaging, the blood flow, as determined from the movement of platelets, was heterogeneous and non-directional in the tumor vessels of liver metastatic xenografts. The blood flow was relatively slower in tumor vessels than normal hepatic sinusoids. At the second TPLSM imaging after chemotherapy, platelet aggregation was observed in tumor vessels of the same mice. Aggregated platelets were frequently adhered to the tumor endothelium, suggesting tumor vessel damage or intratumoral coagulation abnormality by chemotherapy. There was no difference in chemotherapeutics with regard to these findings. Conclusions: Intravital TPLSM imaging of tumor microcirculation at metastatic tumor xenografts is a useful tool to evaluate anti-angiogenic drugs in preclinical models.
Base Pairs to Populations
Authors: Susan E. Bates
Journal: Clinical Cancer Research (2017)

“There is much work to be done and many challenges exist in our mission to end the suffering that breast cancer brings.” So conclude Guest Editors Ann Partridge and Lisa Carey in their overview for this CCR Focus on breast cancer. Oncologists treating rare or treatment-refractory cancers, such as gastric, pancreatic, or hepatocellular cancer, may look with envy at the treatment options available for breast cancer and the progress made in understanding the disease. Yet this CCR Focus shows how sometimes in medicine, answers to questions may only deepen our understanding and lead to more difficult questions. We have found mutations that may be oncogenic drivers but lack insight as to the cause of these mutations, given that our best-understood carcinogens, tobacco and UV radiation, are not culprits. Are the mutations random, or is there an underlying causative mechanism? We have developed treatments for breast cancer that have added years to life but have yet to understand why some tumors respond and others do not. We need an understanding so that we may apply our current therapies to various tumor subtypes. And we have witnessed the emergence of immunotherapy options for lung and kidney cancer, but to date, these novel alternatives have not delivered their promise in breast cancer. Most importantly, we face the daunting task of getting these therapies to everyone who needs treatment. The World Health Organization Model Lists of Essential Medicines is designed to help underresourced countries decide which medications should be prioritized. Trastuzumab, with its proven track record and ability to prolong life in a meaningful quantity, was only added to the list in 2015 but is still not available in many low- and middle-income countries (1, 2). Solving global health care disparities will likely prove the most difficult of all these challenges.In “Breast Cancer Research: From Base Pairs to Populations,” Ann Partridge and Lisa Carey lay out the diverse challenges created by biomedical progress. They have recruited experts in the field, basic scientists, immunologists, oncologists, and epidemiologists, to discuss these challenges, all with the shared goal to improve breast cancer outcomes. As with every CCR Focus, we hope to inform those who are interested but not expert and inspire those already working in the field.Susan E. BatesDeputy Editor, CCR FocusColumbia University Medical CenterSee all articles in this CCR Focus section, “Breast Cancer Research: From Base Pairs to Populations.”
Abstract P204: Sex Differences and the Role of Estrogen Receptor β in Exercise-Induced Myocardial Hypertrophy
Authors: Elke Dworatzek, Shokoufeh Mahmoodzadeh, Eva Brozová, Karina Nawrath, Carola Schubert, Jan-Ake Gustafsson, Vera Regitz-Zagrosek
Journal: Circulation Research (2011)

We and others found sex differences in physiological myocardial hypertrophy (MH) in mice subjected to voluntary cage-wheel running (VCR) and forced exercise training. Female mice showed significantly more MH, suggesting the involvement of estrogen (E2) and estrogen receptors (ER). We therefore investigated the underlying mechanisms leading to sex differences in physiological MH and the role of E2 and ER beta (ERß). Male and female C57/Bl6 wild-type (WT) and ERß-deficient mice (ERß-/-) at the age of 12 weeks performed 8 weeks of VCR or were kept sedentary (sed). Exercise performance was monitored daily and left ventricular mass (LVM) was examined by echocardiography. RNA and protein were analyzed by Real-Time PCR and western blot. Luciferase-reporter Assays were performed with PGC-1a-, MEF2A- and MEF2C-promoter deletion constructs in a human cardiac myocyte cell line (AC16 cells) with/without E2 treatment. Female WT-mice run more than their male counterparts (6.7km/day vs. 4.2km/day; p&lt;0.001). Females showed significant greater increase in LVM and cardiomyocyte diameter in response to exercise compared to males. VCR led to a significant activation of AKT and p38-MAPK signalling in female running-mice, but not in males. Mitochondrial biogenesis associated genes MEF2A and ATP5K mRNA expression were significantly higher in female VCR mice. Female and male ERß-/- mice showed similar running performance compared with WT-mice (6.3km/day vs. 2.7km/day; respectively; p&lt;0.001); however they showed no changes in LVM compared to sed-controls. In contrast to WT animals, female ERß-/- mice showed no increase in AKT and p38-MAPK phosphorylation or up-regulation of mitochondrial key enzymes. E2-treatment of AC16 cells up-regulated mitochondrial target genes (PGC-1a, MEF2A NRF1/2 and TFAM) and led to nuclear translocation of PGC-1a. E2 increased transcriptional activity of PGC-1a and MEF2A/C in an ER dependent manner in cardiomyocytes. Female hearts develop more physiological MH due to exercise, characterized by a stronger activation of pathways and genes involved in the regulation of mitochondrial function. ERß is necessary for the development of physiological hypertrophy and for the activation of p38- MAPK and AKT pathways in female mice.
Rogue surgeon Paterson is sentenced to 15 years after performing unnecessary operations
Authors: Clare Dyer
Journal: BMJ (2017)

The rogue breast surgeon Ian Paterson has been sentenced to 15 years in prison for carrying out “extensive, life changing operations for no medically justifiable reason.”

Paterson, a former consultant surgeon at Heart of England NHS Trust, was convicted last month at Nottingham Crown Court of 17 counts of wounding with intent and three counts of wounding in his treatment of nine women and one man.1 He received 15 years for each wounding with intent charge and four years for each wounding charge, all to run concurrently.

The 10 patients underwent needless operations for breast surgery at private hospitals run by Spire Healthcare after Paterson misrepresented biopsy results and exaggerated risks posed by family history to convince the patients that mastectomy was essential to prevent breast cancer. …
Combination Therapy with Bortezomib or Carfilzomib and Selinexor Induces Nuclear Localization of Ikbα and Overcomes Acquired Proteasome Inhibitor Resistance in Human Multiple Myeloma
Authors: Joel G Turner, Trinayan Kashyap, Jana L Dawson, Juan A Gomez, Alexis Bauer, Steven Grant, Yun Dai, Kenneth H. Shain, Mark B Meads, Yosef Landesman, Daniel M Sullivan
Journal: Blood (2016)
<i>Notes from the Field: Veillonella</i>Misidentified as<i>Francisella tularensis</i>— Idaho, 2016
Authors: Kris K. Carter, Erin M. Peterson, Robert L. Voermans, Kenneth S. Anderson, Tamara Cox, Ahmed M. Kassem, Christopher L. Ball, Christine G. Hahn
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Tier 1 select agents are biologic agents and toxins that present the greatest risk for deliberate misuse with significant potential for mass casualties or devastating effects to the economy, critical infrastructure, or public confidence, and pose a severe threat to public health and safety.
Shortened multidrug-resistant tuberculosis regimens overcome low-level fluoroquinolone resistance
Authors: Armand Van Deun, Chen-Yuan Chiang
Journal: European Respiratory Journal (2017)

We read the research letter by Javaid et al . [1] with great interest. The recommendations from the World Health Organization (WHO) on the use of shortened multidrug-resistant tuberculosis (MDR-TB) regimens controversially indicated that "shortened MDR-TB regimens should not be used in patients who have documented or likely resistance to medicines in the regimen" [2], leading to the concept that MDR-TB patients with additional resistance to not only fluoroquinolones (FQs) or second-line injectables (SLIs), but also ethambutol (EMB), prothionamide (Pto) and pyrazinamide (PZA) would not be eligible for the regimens [3]. This is a highly conservative approach that will greatly limit the applicability of shortened MDR-TB regimens and deprive many MDR-TB patients in high-burden countries of short and highly effective regimens. The 9-month MDR-TB regimen piloted in Bangladesh comprised high-dose gatifloxacin (hGfx), clofazimine (Cfz), EMB and PZA throughout, supplemented by kanamycin (Km), Pto and high-dose isoniazid (hINH) during an intensive phase [4]. The regimen was initially designed to be used in settings with limited resources, where drug susceptibility testing was not available in a timely manner. It was designed as a standardised regimen, using clofazimine and first-line drugs to replace toxic and less effective second-line drugs such as cycloserine and para-aminosalicylic acid. The drugs that are crucial in achieving sputum conversion are hGfx and Km, and those crucial in shortening the duration of treatment are hGfx, Cfz and PZA [5]. Other drugs, in combination, play a supportive role and full susceptibility to these drugs was not expected in the original design. Most patients treated with shortened MDR-TB regimens in Bangladesh [4] and other countries [6] have been exposed to EMB for a prolonged period. Those with resistance to EMB were not excluded and replacement of EMB by another drug was not performed. hINH and Pto were combined complimentarily to address cross-resistance to Pto in inhA -mutant strains of Mycobacterium tuberculosis , since the serum level of hINH will exceed the minimum inhibitory concentration (MIC) of strains with inhA mutation by a wide margin, ensuring that at least one of hINH and Pto will be effective in most cases. Resistance to Pto was not associated with an unfavourable outcome [4] and hINH may also be able to suppress a substantial proportion of bacilli with katG mutation. Shortened unmodified MDR-TB regimens using high-dose gatifloxacin overcome low-level fluoroquinolone resistance <http://ow.ly/VCHF30bt4kA>
Risk of Bleeding in 9,429 Patients with Philadelphia-Negative Myeloproliferative Neoplasms: a Population-Based Study from Sweden
Authors: Maria Creignou, Hannah Bower, Therese M-L Andersson, Anna Ravn Landtblom, Paul W Dickman, Magnus Björkholm, Sigurdur Y Kristinsson, Malin Hultcrantz
Journal: Blood (2016)
Impact of gender on survival of patients (pts) with hepatocellular carcinoma (HCC): A SEER analysis.
Authors: Dongyun Yang, Josh Usher, Jordan LoCoco, Chaudhari Pritesh, Heinz-Josef Lenz, Anthony B. El-Khoueiry
Journal: Journal of Clinical Oncology (2013)

4128 Background: The incidence of HCC is significantly higher in males (M) than females (F). Preclinical models suggest a role for estrogen in attenuating progression of HCC by various mechanisms such Il-6 suppression or estrogen receptor α-mediated inhibition of NF-κB activity. We investigated the impact of age and gender on survival in patients with HCC using the SEER data. Methods: We identified all patients diagnosed with HCC (ICD-O-3 Site code C22.0 and Histology Code 8170-8175) from 1988 to 2009 from the SEER registry. Pts with information on gender, age, ethnic background, and staging were included in the analysis. Exclusion criteria included fibrolamellar histology, diagnosis at autopsy or by death certificate, and absence of survival data. Hazard ratios (HR) for survival were derived using Cox regression model adjusted for race, year of diagnosis, marital status, treatment, birthplace, differentiation and tumor size. Results: A total of 38,250 pts were identified; 76% males; 50% White, 12% African American, 21% Asian, 16% Hispanic, and 1% Native American. 45% had liver limited disease (44%M, 50%F), 37% had macrovascular invasion (37%M, 35%F), 18% had metastatic disease (19%M, 15%F). Treatment information was available for pts diagnosed after 1998 (n=32,938): 11% received liver directed therapy, 11% had surgical resection, and 7% underwent liver transplantation. Median age at diagnosis was 61 years for M versus 68 years for F. HR for OS of F versus M was 0.83 (95%CI:0.78-0.89) for pts &lt; 55 years old. In contrast, the OS HR of F versus M was 0.95 (95%CI:0.92-0.98) for pts ≥ 55 years old and 0.98 (95%CI: 0.94-1.01) for pts ≥ 65 years old. The F vs. M (&lt;55 yrs old) HR for OS by stage of disease was: liver limited disease: HR 0.90, CI: 0.81-1.01; macrovascular invasion: HR 0.81, CI: 0.73-0.89; metastatic disease, HR 0.80, CI: 0.70-0.92. Conclusions: Females under the age of 55 appear to have superior survival compared to males with HCC based on a SEER data analysis. This finding is in line with preclinical reports of estrogen attenuation of HCC development and progression.