tbuckley/cabot-search huggingface dataset:
Diabetes as a predictor of colon cancer prognosis: A single institution based retrospective data analysis.
Authors: Nischala Ammannagari, Anush V. Patel, Eric N. Bravin, Melissa Scribani, Jennifer Victory
Journal: Journal of Clinical Oncology (2013)

e14709 Background: Prevalence of Diabetes mellitus (DM) has increased in dramatic proportions globally over last few decades. Several observational epidemiological studies have shown increased risk of colorectal malignancies in patients with DM. However, it is not yet clearly understood if DM can impact the prognosis of colon cancer. Methods: The hospital’s cancer registry was used to identify advanced (stage III or IV) colon cancer cases diagnosed from January 2007 to December 2009. To be included in the study, the patient must have been treated with a 5-Fluoro Uracil based chemotherapy regimen. Retrospective chart review of electronic medical records was used to collect patient characteristics, including diabetes mellitus (DM) status. Kaplan-Meier curves were constructed for disease free survival and overall survival time. These survival curves were compared between diabetics and non-diabetics using the log rank test. Results: A total of 40 subjects met inclusion criteria, with a mean age of 64.6 years. Compared to non-diabetic patients, patients with diabetes had significantly poorer disease free survival (p=0.03). There was no difference in overall survival when comparing diabetic patients to non-diabetics (p=0.47). Conclusions: While taking into consideration that the study was under powered due to the small sample size, this study does raise the possibility that diabetes mellitus might be an important prognostic indicator of colon cancer. Management of diabetes must be emphasized as an integral part of care of colon cancer.
Prevalence of anemia and compliance to the National Comprehensive Cancer Network guidelines for workup and treatment of anemia among patients with gynecologic malignancies.
Authors: Demetra Hufnagel, Sumit Mehta, Chinyere Ezekwe, Alaina J. Brown, Lauren S. Prescott
Journal: Journal of Clinical Oncology (2019)

32 Background: The National Comprehensive Cancer Network (NCCN) recommends prompt evaluation of anemic patients with hemoglobin (Hb) ≤ 11g/dL. There are a paucity of studies evaluating compliance with the NCCN guidelines. Our objective was to investigate the prevalence of anemia among patients diagnosed with gynecologic cancers and assess compliance with NCCN guidelines. Methods: We performed a retrospective cohort study of patients diagnosed and treated with gynecologic cancer at our institution from 2008-2018. Tumor-registry-confirmed cancer cases were identified using ICD codes from the Synthetic Derivative (SD) database which is a de-identified copy of our institution’s electronic medical record. Patients were included if they were between the ages of 18 and 89, had their initial care at our institution, and had a Hb within the first 6 months of diagnosis. Dual primaries were excluded. Anemia was defined as Hb ≤ 11g/dL. Anemia was graded using the CTCAE v.4.0. Absolute and possible iron deficiency were defined by NCCN Guidelines. Results: We identified 1031 patients who met our inclusion criteria. The median age was 61 years (range 20 - 86). The most common malignancy was uterine cancer 509 (49%) followed by ovarian 262 (25%), cervical 133 (13%), vulvar 107 (10%) and vaginal 20 (2%). Of the 1031 patients in our study, 662 (64%) were noted to be anemic within six months of diagnosis. Of these patients 128 (19%) were noted to have grade 1, 309 (47%) grade 2, and 225 (34%) grade 3 anemia. Of those who were anemic, 90 (14%) underwent any workup for anemia, of which 63 (10%) had iron studies performed. Of those with iron studies performed, 7 (1%) patients had absolute iron deficiency and 24 (4%) had possible iron deficiency. Despite the small percentage of individuals with anemia evaluation, 266 (34%) patients received treatment of anemia. Treatments included: oral iron 47 (7%), IV iron 6 (1%), and blood transfusion 213 (32%). Conclusions: Anemia is pervasive among gynecologic cancer patients, but compliance with NCCN guidelines is low. Our data suggest there are opportunities for improvement in evaluation and management of anemia among gynecologic cancers.
Chemogenomic Profiling of Complex Karyotype AML Reveals a Novel Susceptibility to G2/M Checkpoint Inhibition Mediated By HMGA2 Overexpression
Authors: Céline Moison, Vincent-Philippe Lavallee, Clarisse Thiollier, Jean-Francois Spinella, Isabel Boivin, Sébastien Lemieux, Anne Marinier, Josée Hébert, Guy Sauvageau
Journal: Blood (2018)
Dynamic Mitochondrial Responses to Oxidative Stress in Primary AML Cells Involve Structural Damage and Repair Activity.
Authors: Myung-Geun Shin, Hye-Ran Kim, Hyeoung-Joon Kim, Mi-Ji Kim, Kook Hoon, Tai-Ju Hwang, Jong-Hee Shin, Soon-Pal Suh, Dong-Wook Ryang
Journal: Blood (2007)
Abstract 576: Phosphodiesterase 2 in Cardiac Arrhythmias and Heart Failure
Authors: Mirna S Fahmi, Mario Günscht, Johannna Siegert, Fabian Dutt, Stephan Künzel, Kristina Lorenz, Michael Wagner, Susanne Kämmerer, Ali El-Armouche
Journal: Circulation Research (2019)

Heart failure (HF) patients often suffer from lethal ventricular arrhythmias leading to sudden cardiac arrests. Phosphodiesterase 2 (PDE2), a cGMP activated enzyme hydrolyzing cAMP, is upregulated in HF. Cardiac-specific PDE2 overexpression revealed strong anti-arrhythmic and heart rate lowering effects of PDE2. Here, we validated the cardioprotective role of PDE2 upon modulating cardiac PDE2 activity, first, via assessing cardiac function of cardiac-specific PDE2-KO mice and second, via potentiating PDE2 mediated cGMP/cAMP crosstalk using natriuretic peptide type C (CNP), which are upstream of the cGMP/PDE2 axis. Cardiac function and arrhythmia susceptibility of PDE2-KO were assessed via echocardiography and ECG telemetry under basal conditions and after myocardial infarction (MI). Patch clamp technique was used to investigate CNP effects on action potentials and ion currents in WT isolated cardiomyocytes and in-vivo via ECG-telemetry. Already under basal conditions, PDE2-KO displayed severe irregularities in RR-intervals. 14 days post MI, PDE2-KO showed lower cardiac function and delayed increase in heart rate after arrhythmia provocation (double isoprenaline (ISO) injection (2 mg/kg i.p.) compared to WT controls, indicating diminished cardiac responsiveness. On the other hand, CNP treatment in WT displayed a PDE2-dependent antiarrhythmogenic effect. CNP (1 μM) significantly reduced the total number of delayed afterdepolarizations and spontaneous action potentials upon acute ISO (10 nM) stimulation. Furthermore, CNP significantly reduced the ISO-mediated increase of the L-type Ca 2+ and late Na + currents as well as SR Ca 2+ waves. These effects were reversed upon specific PDE2 inhibition with BAY 60-7550. Finally, in vivo, CNP (33 μg/g i.p.) significantly reduced the number of ventricular extrasystoles after arrhythmia provocation. This effect was significantly attenuated after PDE2 inhibition with BAY 60-7550. Here we provide evidence for acute antiarrhythmic effects of CNP upon downstream stimulation of cGMP-stimulated PDE2 and a critical role of PDE2 on heart rate regulation. Therefore, pharmacologically enhancing myocardial PDE2 activity may represent a novel cardioprotective strategy in cardiac arrhythmia and HF.
Abstract 287: Altered Mitochondrial Flash Activity and mPTP Opening in the Aged Heart Are Reversed by Elamipretide Treatment
Authors: Huiliang Zhang, Hazel Szeto, Nathan Alder, Peter S Rabinovitch
Journal: Circulation Research (2019)

Rationale: The mitochondrial theory of aging pinpoints mitochondria as the major reactive oxygen species (ROS) production site and target of oxidative stress during aging. Mitochondrial flash (mitoflash) is recently discovered excitable event that is a manifestation of ROS production combined with pH change and coupled with mitochondrial permeability transition pore (mPTP) opening. Our preliminary data shown that 8-week SS-31 peptide (elamipretide) protects the functional performance of the aged mouse heart. This study aims to investigate mitoflash activity and mPTP opening in the aged heart, especially whether and how SS-31 protects the heart function involving modulation of these activities. Methods and Results: By using confocal microscopy imaging on the isolated rat cardiomyocytes with overexpression of mitochondrial targeted cpYFP, we found mitoflash activity in the cells from old (26 mo) was higher than that in young (5 mo) rat cells (2.2 ± 0.2 in old vs 1.3 ± 0.2 in young, /1000μm 2 /100s, n=27-64, p&lt;0.05). SS-31 10 μM treatment normalized the mitoflash activity to the young level. Similarly, by photon-excitation induced mPTP opening, we found that aging increased the mPTP opening and 1 μM SS-31 stabilized the mPTP. Furthermore, by using Seahorse Assay on intact primary isolated cardiomyocytes, we found mitochondrial basal respiration in cells from old mice was higher than that in young mouse cells, however, the maximal respiration rate was without significant difference. The increased basal respiration was attributed to a higher proton leak in old cardiomyocytes (131 ± 14 in 24 month vs 94 ± 11 in young, pmol/min/800cells, n=17-35, p&lt;0.05). Interestingly, acute (2 hrs) in vitro treatment of the old cardiomyocytes with SS-31 100 nm decreased proton leak. Moreover, SS-31 (100 nM) decreased the superoxide production as measured by ratio of MitoSOX Red to MitoTrackerGreen. Conclusion: These results indicate that SS-31 directly protects cardiac aging through rapid rejuvenation of mitochondrial respiration in cardiomyocytes, and in particular, by reducing proton leak, mitochondrial flash activity, and decreasing the mPTP opening. This study helps to uncover the mechanism of the cardiac aging and the protective effect from SS-31 treatment.
Radiation Oncology Incident Learning System (RO-ILS): Increasing stakeholder participation for safety and quality improvement.
Authors: Carl Nelson, Lori Ann Roy, H. James Wallace
Journal: Journal of Clinical Oncology (2019)

232 Background: RO-ILS was launched in 2014 and is free, web-based and in more than 500 U.S. radiation facilities. After RO-ILS was implemented at University of Vermont Medical Center (UVMMC), reporting of radiation incidents decreased and participation by radiation staff was limited. To improve incident reporting and participation, RO-ILS was relaunched for all radiation staff members at UVMMC with emphasis on improved system access and education on RO-ILS programmatic goals. Methods: Prior to RO-ILS, safety/quality incidents at UVMMC were submitted by radiation therapists, dosimetrists and physics staff on paper forms and reviewed monthly by the Radiation Quality Committee. After implementation of RO-ILS in 2016, RO-ILS incidents were reviewed by the UVMMC RO-ILS administrators with no formalized staff feedback. Due to decreasing staff submissions, RO-ILS relaunched September 2018 with increased training, scheduled submission review to radiation staff and identification of department champions. Results: Between April 2014 and May 2019, 270 radiation incidents were reported. Prior to RO-ILS, a median 8 incidents were reported per quarter but decreased to 6 per quarter after RO-ILS. After RO-ILS relaunch, median reported incidents increased to 42 per quarter. Radiation “Near Miss” events pre RO-ILS, post RO-ILS and with RO-ILS relaunch were reduced from 78% to 34% to 9%, while “Operational/Process Improvement” submissions increased from 17% pre RO-ILS to 49% post RO-ILS to 81% after relaunch. After RO-ILS relaunch, staff participation expanded to physicians, nursing and administrative staff for the first time, and physician participation increased from 0 to 50%. Conclusions: Following implementation of RO-ILS at UVMMC, radiation incident reporting initially decreased and the proportion of “Near Miss” reports decreased. After relaunch of RO-ILS, there was substantial increase in incident reporting involving all staff. As RO-ILS evolves at UVMMC, there is continued decrease in near misses and greater emphasis on “Process Improvement”. Continued education, reporting and feedback from RO-ILS submissions is recommended to maintain this high staff participation level.
The Value Proposition for Pediatric Care
Authors: Patricia Flanagan, Patrick M. Tigue, James Perrin
Journal: JAMA Pediatrics (2019)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
A20 in Myeloid Cells Protects Against Hypertension by Inhibiting Dendritic Cell-Mediated T-Cell Activation
Authors: Xiaohan Lu, Nathan P. Rudemiller, Yi Wen, Jiafa Ren, Gianna E. Hammer, Robert Griffiths, Jamie R. Privratsky, Bo Yang, Matthew A. Sparks, Steven D. Crowley
Journal: Circulation Research (2019)

The ubiquitin-editing protein A20 in dendritic cells (DCs) suppresses NF-κB (nuclear factor-κB) signaling and constrains DC-mediated T-cell stimulation, but the role of A20 in modulating the hypertensive response requires elucidation.Here, we tested the hypothesis that A20 in CD11c-expressing myeloid cells mitigates Ang II (angiotensin II)-induced hypertension by limiting renal T-cell activation.Mice with heterozygous deletion of A20 in CD11c-expressing myeloid cells (DC ACT[Cd11c-Cre+A20flox/wt]) have spontaneous DC activation but have normal baseline blood pressures. In response to low-dose chronic Ang II infusion, DC ACT mice compared with WT (wild type) controls had an exaggerated hypertensive response and augmented proportions of CD62LloCD44hi effector memory T lymphocytes in the kidney lymph node. After 10 days of Ang II, DC ACT kidneys had increased numbers of memory effector CD8+, but not CD4+ T cells, compared with WTs. Moreover, the expressions of TNF-α (tumor necrosis factor-α) and IFN-γ (interferon-γ) were upregulated in the DC ACT renal CD8+ T cells but not CD4+ T cells. Saline challenge testing revealed enhanced renal fluid retention in the DC ACT mice. DC ACT kidneys showed augmented protein expression of γ-epithelial sodium channel and NHE3 (sodium-hydrogen antiporter 3). DC ACT mice also had greater reductions in renal blood flow following acute injections with Ang II and enhanced oxidant stress in the vasculature as evidenced by higher circulating levels of malondialdehyde compared with WT controls. To directly test whether enhanced T-cell activation in the DC ACT cohort was responsible for their exaggerated hypertensive response, we chronically infused Ang II into lymphocyte-deficient DC ACT Rag1 (recombination activating protein 1)-deficient (Rag1-/-) mice and WT (Cd11c-Cre-A20flox/wt) Rag1-/- controls. The difference in blood pressure elevation accruing from DC activation was abrogated on the Rag1-/- strain.Following stimulation of the renin-angiotensin system, A20 suppresses DC activation and thereby mitigates T-cell-dependent blood pressure elevation.
Phase I Study of Continuous-Infusion Nelarabine in Patients with Advanced Lymphoid Malignancies
Authors: Tapan Kadia, Varsha Gandhi, Deborah A. Thomas, Farhad Ravandi, William Plunkett, Mary L Ayres, Yuling Chen, Gracy Zacharian, Gautam Borthakur, Hagop M. Kantarjian, Michael J Keating
Journal: Blood (2011)
Gastric Cancer Clinical Practice Guidelines
Authors: _ _
Journal: Journal of the National Comprehensive Cancer Network (2006)

Gastric carcinoma is rampant in many countries around the world. An estimated 36,380 new cases of upper GI carcinomas and 25,120 deaths from these tumors will occur in the United States in 2005. These guidelines provide a systematic approach to gastric cancer and discuss advances in staging procedures such as laparoscopy and endoscopic ultrasonography and in possible functional imaging techniques. The guidelines also discuss the new standard in the United States: combination chemotherapy and radiotherapy in the adjuvant setting for a select group of patients. For the most recent version of the guidelines, please visit NCCN.org
Daily step counts to predict hospitalizations during concurrent chemoradiotherapy for solid tumors.
Authors: Elena Izmailova, Chengrui Huang, Matthew Cantor, Robert Ellis, Nitin Ohri
Journal: Journal of Clinical Oncology (2019)

293 Background: Wearable activity trackers could be useful tools in cancer care. Potential gains include better selection of patients fit for aggressive treatment, improved evaluation of patients during treatment, and provision of enhanced supportive care for patients. In a pilot study, low daily step counts were associated with increased risk for hospital admission during concurrent chemoradiotherapy for solid tumors of the head/neck, lung, or gastrointestinal tract. Here we seek to refine those findings using a larger patient cohort. Methods: Study subjects wore a commercial fitness tracker during a course of concurrent chemoradiotherapy. Patient characteristics, daily step counts, and hospital admissions between the initiation and completion of radiotherapy were tabulated. EORTC QLQ-C30 questionnaires were completed weekly, and summary QoL (range: 0-100) for each subject and week were calculated. Cox regression models with time-dependent and time-fixed covariates were used to identify predictors of first hospital admission during the radiotherapy course. Results: 188 subjects from three trials met inclusion criteria. The most common cancer diagnoses were head and neck (31%), lung (28%), and a gastrointestinal (30%, most commonly rectal [10%] or esophageal [6%]). Median age was 61 (range: 27-90). Baseline ECOG performance status was 0 for 46% of subjects, 1 for 47%, and 2 for 7%. The median patient compliance of wearing activity trackers and contributing data was 98%; 38subjects (20%) were hospitalized during the radiotherapy course. Cox regression demonstrated a 36% reduction in the risk of hospitalization for every 1000 daily steps (averaged over the past 3 days; hazard ratio 0.62, 95% confidence interval 0.48-0.81, p=0.0005). Diagnosis, age, baseline performance status, and QoL score were not statistically significant predictors of hospitalization risk. Conclusions: Continuous activity monitoring with wearable devices during concurrent chemoradiotherapy is feasible. We have validated daily step counts as dynamic predictors of hospitalization risk during treatment. Interventional trials should leverage activity data to optimize supportive care during cancer therapy.
Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study
Authors: Marie-Christine Vantyghem, Mikael Chetboun, Valéry Gmyr, Arnaud Jannin, Stéphanie Espiard, Kristell Le Mapihan, Violeta Raverdy, Nathalie Delalleau, François Machuron, Thomas Hubert, Marie Frimat, Eric Van Belle, Marc Hazzan, Pascal Pigny, Christian Noel, Robert Caiazzo, Julie Kerr-Conte, François Pattou
Journal: Diabetes Care (2019)

OBJECTIVE The long-term outcome of allogenic islet transplantation is unknown. The aim of this study was to evaluate the 10-year outcome of islet transplantation in patients with type 1 diabetes and hypoglycemia unawareness and/or a functioning kidney graft. RESEARCH DESIGN AND METHODS We enrolled in this prospective parallel-arm cohort study 28 subjects with type 1 diabetes who received islet transplantation either alone (ITA) or after a kidney graft (IAK). Islet transplantation consisted of two or three intraportal infusions of allogenic islets administered within (median [interquartile range]) 68 days (43–92). Immunosuppression was induced with interleukin-2 receptor antibodies and maintained with sirolimus and tacrolimus. The primary outcome was insulin independence with A1C ≤6.5% (48 mmol/mol). Secondary outcomes were patient and graft survival, severe hypoglycemic events (SHEs), metabolic control, and renal function. RESULTS The primary outcome was met by (Kaplan-Meier estimates [95% CI]) 39% (22–57) and 28% (13–45) of patients 5 and 10 years after islet transplantation, respectively. Graft function persisted in 82% (62–92) and 78% (57–89) of case subjects after 5 and 10 years, respectively, and was associated with improved glucose control, reduced need for exogenous insulin, and a marked decrease of SHEs. ITA and IAK had similar outcomes. Primary graft function, evaluated 1 month after the last islet infusion, was significantly associated with the duration of graft function and insulin independence. CONCLUSIONS Islet transplantation with the Edmonton protocol can provide 10-year markedly improved metabolic control without SHEs in three-quarters of patients with type 1 diabetes, kidney transplanted or not.
Pre-Emptive Donor Lymphocyte Infusions (DLI) Lead to High Cure Rates in T-Cell Depleted Allogeneic Haemopoietic Stem Cell Transplants for MDS/AML
Authors: Pramila Krishnamurthy, Victoria T Potter, ZiYi Lim, Austin G Kulasekararaj, Aloysius Y Ho, Judith C. W. Marsh, Robin M. Ireland, Stephen Devereux, Antonio Pagliuca, Ghulam J. Mufti
Journal: Blood (2011)
A trainee-led quality improvement project to improve rates of palliative care utilization in patients with advanced cancer.
Authors: Ramy Sedhom, Arjun Gupta, Mirat Shah, Kristen Marrone, Ilene S. Browner, Thomas J. Smith
Journal: Journal of Clinical Oncology (2019)

51 Background: ASCO guidelines recommend palliative care (PC) referral for patients with advanced or metastatic cancer. Despite this, implementation has considerable hurdles. 1st year oncology fellows at our institution identified low rates of palliative care in their longitudinal clinic as an avenue for improvement. Methods: A Fellow-led multidisciplinary team aimed to increase palliative care utilization for patients with advanced cancer followed in first-year fellows’ clinic from baseline 11.5% (5/43 patients, Jul-Dec, '18) to 30% over a 4-mo period. Utilization was defined as evaluation in the outpatient palliative care clinic hosted in the cancer center. The team identified several barriers to referral: orders difficult to find in EMR, multiple consulting mechanisms (EMR, by phone, in person), EMR request not activating formal consult, no centralized scheduler to contact/confirm appointment, and poor awareness of team structure. PDSA cycles were implemented based on identified opportunities. Data were obtained from the EMR. Results: The PDSA cycle included focus groups with stakeholders, standardizing referral process via single order set, identifying a single scheduler with bidirectional communication, and dissemination of process changes. The PDSA was implemented Jan-Apr '19. Rates of palliative care use increased from 11.5% pre-intervention to 43% (27/62 patients) post-intervention. In addition, median time to evaluation in palliative care clinic after placing a consult improved from 23 days (range, 10-60 days) to 12 days (range, 6-19 days). Conclusions: A multidisciplinary approach and classic QI methodology improved palliative care use for patients with advanced cancer. The pilot succeeded given the small number of fellows, buy-in from stakeholders, and institutional support of efforts. Straightforward EMR interventions and ancillary staff use are effective in addressing under referrals.