tbuckley/cabot-search huggingface dataset:
Association of Increasing Use of Mechanical Ventilation Among Nursing Home Residents With Advanced Dementia and Intensive Care Unit Beds
Authors: Joan M. Teno, Pedro Gozalo, Nita Khandelwal, J. Randall Curtis, David Meltzer, Ruth Engelberg, Vincent Mor
Journal: JAMA Internal Medicine (2016)

Mechanical ventilation may be lifesaving, but in certain persons, such as those with advanced dementia, it may prolong patient suffering without a clear survival benefit. To describe the use and outcomes of mechanical ventilation and its association with the increasing numbers of intensive care unit (ICU) beds in the United States for patients with advanced dementia residing in a nursing home 120 days before that hospital admission. This retrospective cohort study evaluated Medicare beneficiaries with advanced dementia hospitalized from January 1, 2000, to December 31, 2013, using the Minimum Data Set assessments linked with Medicare part A claims. A hospital fixed-effect, multivariable logistic regression model examined the effect of changes in ICU beds within individual hospitals and the likelihood of receiving mechanical ventilation, controlling for patients' demographic characteristics, function, and comorbidities. Mechanical ventilation. From 2000 to 2013, a total of 635 008 hospitalizations of 380 060 eligible patients occurred (30.5% male and 69.5% female; mean [SD] age, 84.4 [7.4] years). Use of mechanical ventilation increased from 39 per 1000 hospitalizations in 2000 to 78 per 1000 hospitalizations in 2013 (P < .001, test of linear trend). As the number of ICU beds in a hospital increased over time, patients with advanced dementia were more likely to receive mechanical ventilation (ie, adjusted odds ratio per 10 ICU bed increase, 1.06; 95% CI, 1.05-1.07). In 2013, hospitals in the top decile in the number of ICU beds were reimbursed $9611.89 per hospitalization compared with $8050.24 per hospitalization in the lower decile (P < .001) without an improvement in 1-year mortality (65.2% vs 64.6%; P = 54). Among hospitalized nursing home residents with advanced dementia, we found an increase in the use of mechanical ventilation over time without substantial improvement in survival. This increase in the use of mechanical ventilation was associated with an increase in the number of ICU beds within a hospital.
TCT-214 Pharmacodynamic Effects of Ticagrelor and Eptifibatide Bolus-Only vs. Ticagrelor and Eptifibatide Bolus plus 2 h Infusion in Patients with Acute Coronary Syndrome
Authors: Moazez Marian, Mustafa Ahmed, Firas Al Soliman, Oluseun Alli, Mark Sasse, Brigitta C. Brott, Sumanth D. Prabhu, Massoud A. Leesar
Journal: Journal of the American College of Cardiology (2015)
Cetuximab in combination with irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFIRI) in second and third-line treatment of metastatic colorectal cancer (mCRC): Safety and efficacy analysis
Authors: D. M. Smith, J. Legoux, R. Brunet, X. Adhoute, J. Blanc, M. Fonck, V. Vendrely, Y. Becouarn
Journal: Journal of Clinical Oncology (2006)

3558 Background: The Folfiri regimen demonstrated high efficacy and favorable safety profile compared to irinotecan plus bolus 5-FU/FA (IFL regimen) or irinotecan alone. Folfiri is a standard option in first line treatment of mCRC. Cetuximab, an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR), which is commonly expressed in mCRC, is approved in France in combination with irinotecan after failure of an irinotecan-based therapy. We have prospectively evaluated the combination cetuximab-FOLFIRI in patients with mCRC refractory to FOLFIRI administered in first line treatment. Methods: Patients with EGFR-expressing mCRC, who progressed following first line treatment with FOLFIRI regimen were eligible for this study. Treatment consisted of cetuximab (initial dose 400 mg/m 2 followed by 250mg/m 2 /week) combined with FOLFIRI (given every 2 weeks: irinotecan 180 mg/m 2 , FA 400 mg/m 2 and 5-FU 400 mg/m 2 bolus plus 2400 mg/m 2 /46-h infusion) until either disease progression or unacceptable toxicity. Tumor reponse was assessed by CT scan every 2 months (OMS criteria), and adverses events were registered. Results: 41 patients where included from 09/2004 to 11/2005. 78% Male/ 22% Female, mean age 63 years, median KPS 80, 68% colon primary tumour. 5 patients were treated in second line, 24 patients in third line and 12 in fourth line or more. 40 patients are evaluable for response. They were 8 objective responses (20%) and 11 patients with stable disease (27.5%). The median progression free survival was 4,3 months and the median overall survival was 5 months. 61 % of the 41 patients experienced grade 3–4 adverses events, the most frequent of which were leucopenia (16%), asthenia (9%), vomiting and diarrhoea (5%), and acneiform skin rash in 11 patients (24%), severe xerosis (7%). 6/11 patients who experienced acneiform eruption grade 3 were alive at 12 months. Conclusions: The combination of cetuximab with FOLFIRI demonstrated promising efficacy and acceptable safety profile without increasing chemotherapy adverse reactions. A prospective randomised trial would confirm the advantage of FOLFIRI over irinotecan alone in combination with cetuximab. No significant financial relationships to disclose.
Hard Time or Hospital Treatment? Mental Illness and the Criminal Justice System
Authors: Christine Montross
Journal: New England Journal of Medicine (2016)

Interview with Dr. Christine Montross on treatment and confinement of people with serious mental illness. (15:34)Download When a mentally ill person comes into contact with the criminal justice system, the decision about whether that person belongs in jail or in the hospital is rarely a clinical one. But it may shape the course of the person's life for many years to come.
Primary Neuroblastoma Involving Spinal Canal
Authors: Peng Xie, Fuqiang Shao, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2016)

An MRI of the spine was performed in a 5-month-old girl to assess the cause of lower-extremity paralysis. The images showed a left paraspinal mass at the lumbar level invading the spinal canal, which suggested possible neuroblastoma. A subsequent MIBG scan showed abnormal activity in the spinal canal. Neuroblastoma was confirmed pathologically.
Superoxide dismutase activity in doxorubicin-induced cardiotoxicity in humans: A novel tool for risk stratification
Authors: R. P. Pereira, J. F. Fleck, L. E. Rohde, N. Clausell, C. S. Weber, G. Geib, N. G. Mazzotti, A. Bello-Klein
Journal: Journal of Clinical Oncology (2004)

8036 Background: oxidative stress has been implicated in doxorubicin-induced cardio toxicity in experimental studies. The role of oxidative pathways in clinical doxorubicin-induced cardiotoxicity, however, is poorly characterized. We investigated if systemic antioxidant markers predict cardiac dysfunction in patients eligible for doxorubicin use. Methods: we prospectively evaluated oncology patients eligible for doxorubicin chemotherapy, with no prior history of cardiovascular disease. Blood samples for enzymatic (super oxide dismutase activity [SOD-U/mg protein]) and non-enzymatic antioxidants (total radical trapping antioxidant potential [TRAP-μmol of Trolox/mg protein]) were collected at baseline (B), third (T) and final (F) cycles. Left ventricular ejection fraction (LVEF) was assessed by radionuclide ventriculography. Results: Fifty-one patients (49±12 years, 90% female) underwent 5.9 ± .9 chemotherapy cycles and received 301 ± 52 mg/m2 of doxorubicin, mostly for breast cancer (80%). Overall, LVEF decreased from 60.7 ± 6.1% at baseline to 56.4 ± 7.4 % after treatment (p<0.001), but only 6 (12%) patients developed significant LV systolic dysfunction (LVEF<50%). SOD activity increased significantly during treatment (4.5 ± 1.8 [B], 6.0 ± 2.1 [T], 5.6 ± 2.2 [F]; p<0.01), while TRAP values were unchanged (302 ± 120 [B], 312 ± 119 [T], 299 ± 99 [F], NS). Interestingly, baseline SOD values from patient who developed LV systolic dysfunction were significantly higher than those who maintained a normal LVEF (5.9 ± 1.8 versus 4.3 ± 1.7; p<0.05). We also observed a trend toward greater change in SOD values over time in patients who did not developed LV systolic dysfunction (1.7 ± 2 [LVEF≥50%] versus 0.2 ± 3.3 [LVEF<50%]; p=0.14). In multivariate analysis, adjusted for age and doxorubicin dose, baseline SOD activity remained an independent predictor of LV dysfunction. Conclusions: high baseline SOD activity predicts doxorubicin-induced cardio toxicity in humans, in part because recruitment of enzymatic anti-oxidant defense mechanisms may be limited. Non-enzymatic pathways (TRAP) were not predictive of cardiac dysfunction. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Laboratories Roche Laboratories
AB0170 Anti-cyclic citrullinated peptide and rheumatoid factor in patients with chronic hepatitis b and hepatitis b carriers
Authors: E. Dalkilic, M. Kiyici, A. Nizamoglu, A. Ozbek, A. N. Tufan, M. Yurtkuran
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid factor (RF) positivity that may occur in a number of patients with HBV infection poses challenges in terms of differential diagnosis with rheumatoid arthritis (RA). On the other hand, antibodies to cyclic citrullinated peptide (anti-CCP) may prove to be an important marker for differential diagnosis of the two conditions. <h3>Objectives</h3> This study aimed to assess anti-CCP and RF positivity among patients with hepatitis B and rheumatoid arthritis. <h3>Methods</h3> Anti-CCP and RF seropositivity was assessed in 61 patients with HBV infection (32 patients with chronic hepatitis, 29 patients with inactive HBV carrier status), and 40 patients with RA as the control group. <h3>Results</h3> RF positivity was found in 18.7% and 34.4% of the patients with chronic hepatitis B and inactive HBV carrier status, respectively. On the other hand, only one patient with chronic hepatitis B had low positive anti-CCP. RF was positive in 24 (60%) and anti-CCP was positive in 26 (65%) patients among the 40 patients with RA. <h3>Conclusions</h3> Anti-CCP may be helpful in the differential diagnosis between RA and chronic hepatitis B infection or inactive HBV carrier status. <h3>References</h3> Inanc N, Dalkilic E, Kamali S, et al. (2007) Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis. Clin Rheumatol 26, 17-23. Lee SI, Yoo WH, Yun HJ, et al. (2007) Absence of antibody to cyclic citrullinated peptide in sera of non-arthritic patients with chronic hepatitis B virus infection. Clin Rheumatol 26, 1079-82. Lienesch D, Morris R, Metzger A, Debuys P, Sherman K (2005) Absence of cyclic citrullinated peptide antibody in nonarthritic patients with chronic hepatitis C infection. J Rheumatol 32, 489-93. <h3>Disclosure of Interest</h3> None Declared
GW27-e0404 The protective effects of Peroxiredoxin II on cardiac ischemia-reperfusion injury in prxII transgenic mice
Authors: Huimin Wang, Xiao-Jing Shi, Wen-Juan Zhou, Xue-Peng Geng, Ke Yang, Yue Xiao, Kai Tang, Hong-Min Liu, Wen Zhao
Journal: Journal of the American College of Cardiology (2016)
TCT-460 Multi-Center, Randomized Evaluation of the Elixir DESyne® Novolimus Eluting Coronary Stent System with Biodegradable Polymer Compared to a Zotarolimus-Eluting Coronary Stent System: Final 5-Year Results from the EXCELLA BD Study
Authors: Stefan Verheye, Alexandre Abizaid, Roberto Botelho, Ricardo Costa, Luiz Fernando Tanajura, Katsuhisa Waseda, Lynn Morrison, Sara Toyloy, Peter J. Fitzgerald, Joachim Schofer
Journal: Journal of the American College of Cardiology (2016)
Activity-Dependent Changes in Gene Expression in Schizophrenia Human-Induced Pluripotent Stem Cell Neurons
Authors: Panos Roussos, Boris Guennewig, Dominik C. Kaczorowski, Guy Barry, Kristen J. Brennand
Journal: JAMA Psychiatry (2016)

<h3>Importance</h3> Schizophrenia candidate genes participate in common molecular pathways that are regulated by activity–dependent changes in neurons. One important next step is to further our understanding on the role of activity-dependent changes of gene expression in the etiopathogenesis of schizophrenia. <h3>Objective</h3> To examine whether neuronal activity-dependent changes of gene expression are dysregulated in schizophrenia. <h3>Design, Setting, and Participants</h3> Neurons differentiated from human-induced pluripotent stem cells derived from 4 individuals with schizophrenia and 4 unaffected control individuals were depolarized using potassium chloride. RNA was extracted followed by genome-wide profiling of the transcriptome. Neurons were planted on June 21, 2013, and harvested on August 2, 2013. <h3>Main Outcomes and Measures</h3> We performed differential expression analysis and gene coexpression analysis to identify activity-dependent or disease-specific changes of the transcriptome. Gene expression differences were assessed with linear models. Furthermore, we used gene set analyses to identify coexpressed modules that are enriched for schizophrenia risk genes. <h3>Results</h3> We identified 1669 genes that were significantly different in schizophrenia-associated vs control human-induced pluripotent stem cell–derived neurons and 1199 genes that are altered in these cells in response to depolarization (linear models at false discovery rate ≤0.05). The effect of activity-dependent changes of gene expression in schizophrenia-associated neurons (59 significant genes at false discovery rate ≤0.05) was attenuated compared with control samples (594 significant genes at false discovery rate ≤0.05). Using gene coexpression analysis, we identified 2 modules (turquoise and brown) that were associated with diagnosis status and 2 modules (yellow and green) that were associated with depolarization at a false discovery rate of ≤0.05. For 3 of the 4 modules, we found enrichment with schizophrenia-associated variants: brown (χ<sup>2</sup> = 20.68;<i>P</i> = .002), turquoise (χ<sup>2</sup> = 12.95;<i>P</i> = .04), and yellow (χ<sup>2</sup> = 15.34;<i>P</i> = .02). <h3>Conclusions and Relevance</h3> In this analysis, candidate genes clustered within gene networks that were associated with a blunted effect of activity-dependent changes of gene expression in schizophrenia-associated neurons. Overall, these findings link schizophrenia candidate genes with specific molecular functions in neurons, which could be used to examine underlying mechanisms and therapeutic interventions related to schizophrenia.
Close Contact Casting vs Surgery for Unstable Ankle Fractures
Authors: David W. Sanders
Journal: JAMA (2016)

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Intramuscular PEG-Asparaginase At 1000 U/m2 Achieves Adequate Trough Activity Levels in the Majority of Patients Treated on the UKALL 2003 Childhood Acute Lymphoblastic Leukemia (ALL) Protocol
Authors: Caroline YK Fong, Catriona Anne Parker, Adiba Hussain, Jizhong Liu, Monika Essink, Hans Juergen Kuehnel, Donna L Lancaster, Genevieve Pridham, Debbie Payne, Charlotte O'Horo, Shekhar Krishnan, Jeremy Hancock, Nicholas Goulden, Anthony V. Moorman, Sue Richards, Ajay J Vora, Vaskar Saha, Ashish Narayan Masurekar
Journal: Blood (2011)
Tolerance and Response to Initial Systemic Therapy In Older Patients with Multiple Myeloma (MM): Observations From 276 Unselected Recent Cases In the Practices of US-Based Medical Oncologists (MOs)
Authors: Neil Love, Sagar Lonial, Kenneth C. Anderson, Rafael Fonseca, Melanie Elder, Douglas Paley, Kathryn Ziel
Journal: Blood (2010)
GW27-e0070 Is exclusive breastfeeding and its duration related to cardio respiratory fitness in childhood?
Authors: Mohammadreza Vafa, Javad Heshmati, Homa Sadeghi, Farzad Shidfar, Nazli Namazi, Hamidreza Baradaran, Behzad Heydarpour
Journal: Journal of the American College of Cardiology (2016)
The anticancer effects of supinoxin (RX-5902) in renal cell cancer.
Authors: Young Lee, Reza Mazhari, Deog Joong Kim
Journal: Journal of Clinical Oncology (2016)

524 Background: DEAD box RNA helicase DDX5/p68 may play several important roles in cancer. In particular, phosphorylated p68 has been shown to be associated with cell transformation, epithelial mesenchymal transition (EMT), and cell migration, deeming it a promising target for novel anti-cancer therapeutics. We have previously shown that Supinoxin (RX-5902) interacts with phosphorylated p68 on Tyr593, interfering with the phosphorylated p68-β-catenin signaling pathway. Methods: In this study, we first demonstrated anti-proliferative effects in ten renal cancer cell lines with a high level of sensitivity to Supinoxin (IC50 of 39 nM); TK-10 was the only resistant cell line in this study. We also sought to examine the tumor growth inhibition (TGI), tumor growth delay (TGD), and survival benefits of Supinoxin in the human renal cell carcinoma tumor (Caki-1) xenograft mouse model, using two different dosing schemas: weekly dosing at 20-160 mg/kg for 4 weeks, or 50-70 mg/kg daily (5 days on/2 days off) for 3 weeks. Results: Weekly dosing of Supinoxin at 160 mg/kg resulted in a 75% TGD (P &lt; 0.001). Daily administration of Supinoxin resulted in dose-dependent TGI (80 and 96%; Day 21) and TGD (68 and 104%, P &lt; 0.001), and extended the overall survival of the animals at both doses (P &lt; 0.0001). At the dose of 70 mg/kg daily, 6/10 animals demonstrated partial tumor regressions and 1/10 a complete tumor regressions. Supinoxin did not result in a reduction in body weight gain, treatment related deaths, or clinical observations in either of the dosing schemas. Sunitinib (60 mg/kg; daily for 21 days) resulted in TGD for both in vivo studies validating the Caki-1 model herein. Conclusions: These data support the potential therapeutic activity of Supinoxin in renal cell cancers. A Phase I study of Supinoxin on relapse/refractory solid tumors is ongoing (NCT02003092).
Interim Positron Emission Tomography Scan Predicts Early Outcomes Of Patients With Peripheral T-Cell Lymphoma
Authors: Ho-Young Yhim, Na-Ri Lee, Eun-Kee Song, So Yeon Jeon, Chang-Yeol Yim, Yeon-Hee Han, Myung-Hee Sohn, Bohee Lee, Jeong-A Kim, Young Ha Park, Woo Hee Choi, Hee Sun Kim, Jae-Yong Kwak
Journal: Blood (2013)
PX-866 and docetaxel in patients with advanced solid tumors.
Authors: Antonio Jimeno, Neil N. Senzer, Charles M. Rudin, Wen Wee Ma, Balazs Halmos, Ian D. Schnadig, Benjamin Levy, Diana Felice Hausman, Scott Peterson, Luke N. Walker
Journal: Journal of Clinical Oncology (2012)

3024 Background: PX-866, an irreversible pan-isoform inhibitor of Class 1 PI-3K has additive to synergistic effects when combined with docetaxel in xenograft models of NSCLC and SCCHN. A phase I/II study of PX-866 and docetaxel was initiated to further evaluate this combination. Enrollment in phase I is complete, and the randomized, controlled phase II portion is now enrolling patients with either NSCLC or SCCHN. Phase I safety and pharmacokinetics were previously described; the recommended phase II dose of PX-866 was 8 mg daily, the same as the single agent MTD (Jimeno A, et al. AACR-NCI-EORTC, 2011). Updated phase I antitumor and biomarker results are presented here. Methods: Phase 1 consisted of dose escalation of PX-866 at 4, 6, or 8 mg po qd in combination with docetaxel 75 mg/m 2 IV once every 21 days (d). Patients had advanced solid tumors for which docetaxel was compendia listed. Tumor restaging was performed every 2 cycles. Archived tumor biopsies were collected for assessment of potential biomarkers of response, including PIK3CA and KRAS mutations and PTEN expression. Results: 43 pts were enrolled: NSCLC (n=6), prostate (n=5), ovarian (n=5), SCCHN (n=3), and pancreatic (n=3) were the most common tumor types. Median time on study (TOS) was 81 d (5-361), with 9 pts still on study. 16 pts received ≥ 6 cycles (6-17), including 3 pts with NSCLC, and 4 pts with ovarian cancer. Biomarker data are available for 20 evaluable pts. Median days on study by mutational status was: PIK3CA/KRAS WT (n=13): 91 d (28-286); PIK3CA-MUT (n=5): 183 d (64-342); KRAS-MUT (n=3): 141 d (125-361); and PIK3CA/KRAS-MUT (n=2): 96 d (86-105). A trend toward longer TOS was observed in pts with PIK3CA-MUT vs PIK3CA/KRAS-WT (p=0.14). Assessment of PTEN is ongoing. Best response in 32 evaluable pts was 2 PR (6%), 22 SD (69%), and 8 PD (25%). The PRs were in NSCLC and ovarian cancer (both PIK3CA/KRAS WT). 8 other pts had ≥15% tumor shrinkage, including NSCLC (n=2). Conclusions: PX-866 with docetaxel was associated with a disease control rate of 75%, with 50% of evaluable pts demonstrating SD or better for ≥ 6 cycles. Based on available data, a trend for a longer TOS was seen with PIK3CA-MUT pts. This relationship will be further evaluated in phase II.
Successful use of a modified Goeckerman regimen in the treatment of chronic severe atopic dermatitis: A prospective pilot study
Authors: Benjamin Farahnik, Kourosh Beroukhim, Melissa Danesh, Mio Nakamura, Michael Abrouk, Tian Hao Zhu, Rasnik Singh, Kristina Lee, Tina Bhutani, John Koo
Journal: Journal of the American Academy of Dermatology (2016)