tbuckley/cabot-search huggingface dataset:
A model to predict the feasibility of concurrent chemoradiotherapy with temozolomide in glioblastoma multiforme patients over age 65.
Authors: Florian Putz, Sergej Potapov, Godehard Lahmer, Rolf Buslei, Oliver Ganslandt, Marga Lang-Welzenbach, Rainer Fietkau, Sabine Semrau
Journal: Journal of Clinical Oncology (2014)

2040 Background: It is controversial whether concurrent chemoradiotherapy (CRT) with temozolomide is feasible and beneficial in elderly patients with glioblastoma (GBM). Methods: Retrospective analysis of 76 elderly GBM patients (≥ 65 years) treated with concurrent CRT with temozolomide. Factors influencing prognosis and feasibility of CRT were investigated. Results: Median overall survival (mOS) was 11.3 months. Univariate analysis showed a significant difference in mOS for cumulative dose of concurrent temozolomide (optimal cutoff, 2655 mg/m²; 13.9 months for > 2655 mg/m² v 4.9 months for ≤ 2655 mg/m²; P = .0103). Significant independent prognostic parameters in multivariate analysis were: a cumulative dose of concurrent temozolomide > 2655 mg/m² (hazard ratio [HR], 0.41; P = .008), thrombocytopenia grade III/IV (HR, 3.05; P = .034), and biopsy only (HR, 2.10; P = .022). Hematotoxicity was the most common cause of treatment interruption or discontinuation in patients with an insufficient cumulative temozolomide dose. Prognostic factors for successful performance of CRT with a cumulative dose of concurrent temozolomide > 2655 mg/m² were: female gender (odds ratio [OR], 0.208; P = .0103), age (OR, 0.849 per year; P = .0178), and pretreatment platelet count (OR, 1.010 per 1000 platelets/µl; P = .0057). Conclusions: The probability of successful performance of concurrent chemoradiotherapy with temozolomide can be estimated based on the patient's age, sex and pretreatment platelet count using the model developed in this study. Thus, a subgroup of elderly patients with GBM can be identified in whom concurrent chemoradiotherapy with temozolomide is feasible and who have a favorable prognosis.
Abstract 13530: New Insights Into CPR Optimization Through a Flow per Compression Analysis of Chest Compression Generated Blood Flow
Authors: Joshua W Lampe, Tai Yin, George Bratinov, Wes Shoap, Yuxi Lin, Christopher L Kaufman, Lance B Becker
Journal: Circulation (2016)

Introduction: During cardiac arrest and CPR, the two primary pumps of the cardiovascular circuit (the right and left ventricles) are supplanted by a single pump, the chest compression. In pre-clinical experiments, blood flows are reported as the amount of flow per minute (L/min). Characterizing flow on a per minute basis is highly dependent on chest compression (CC) rate. Analysis of flow generated by each compression (“cardiac output” in L/comp) could reveal important information relevant to lung perfusion and how the circuit as a whole is responding to CPR. Hypothesis: It was hypothesized that increasing CC rate would improve per minute blood flow but reduce flow on a per compression basis. Methods: CPR was performed on nine domestic swine (~30 kg) using standard monitoring. Flow was measured in the right common carotid and abdominal aorta. Ventricular fibrillation was electrically induced. Mechanical CC were started after ten minutes of untreated VF. CC were delivered at rates of 50, 75, 100, 125, or 150 compressions per minute (cpm) and a depth of 2” for a total of 54 min. CC rates were changed every 2 min and were randomized. Results: Mean blood flows are shown in L/min (solid line) and L/comp (dashed line) in Figure 1 for minutes 0-10 and 10-20. Across all rates, per minute flows were strongly rate dependent in minutes 0-10, favoring fast rates, and were weakly rate dependent in minutes 10-20, favoring rates near 100 CPM. Across all rates, per compression flow had a weaker rate dependence in minutes 0-10, favoring rates less than 100 CPM, but during minutes 10-20 had a strong rate dependence, also favoring rates less than 100 CPM. Conclusions: While CC rates greater than 100 cpm may provide more total blood flow early during CPR, analysis of blood flow per compression indicates that they can become detrimental after 10 minutes of ongoing CPR. During a prolonged resuscitation, a longer time after a given compression might be needed for venous refill thereby favoring rates of 100 cpm or less.
Improving Decisions About Transport to the Emergency Department for Assisted Living Residents Who Fall
Authors: Jefferson G. Williams, Michael W. Bachman, Michael D. Lyons, Benjamin B. Currie, Lawrence H. Brown, A. Wooten Jones, Jose G. Cabanas, Alan K. Kronhaus, J. Brent Myers
Journal: Annals of Internal Medicine (2017)

Residents of assisted living facilities who fall may not be seriously ill or injured, but policies often require immediate transport to an emergency department regardless of the patient's condition.To determine whether unnecessary transport can be avoided.Prospective cohort study.One large county with a single system of emergency medical services.Convenience sample of residents in 22 assisted living facilities served by 1 group of primary care physicians.Paramedics providing emergency medical services followed a protocol that included consulting with a physician by telephone.The number of transports after a fall and the number of time-sensitive conditions in nontransported patients.Of the 1473 eligible residents, 953 consented to participate in the study (mean age, 86 years; 76% female) and 359 had 840 falls in 43 months. The protocol recommended nontransport after 553 falls. Eleven of these patients had a time-sensitive condition. At least 7 of them received appropriate care: 4 requested and received transport despite the protocol recommendation, and 3 had minor injuries that were successfully managed on site. Three additional patients had fractures that were diagnosed by outpatient radiography. The final patient developed vomiting and diarrhea, started palliative care, and died 60 hours after the fall. At least 549 of the 553 patients (99.3% [95% CI, 98.2% to 99.8%]) with a protocol recommendation for nontransport received appropriate care.The resources required for this program will preclude use in some locations.Shared decision making between paramedics and primary care physicians can prevent transport to the emergency department for many residents of assisted living facilities who fall.None.
Care UK tells GPs about private options for non-NHS funded procedures
Authors: Abi Rimmer
Journal: BMJ (2017)

A private company that provides NHS care has contacted around 300 general practices around Bristol and Devizes to tell them about a new “self pay” option for procedures that are not available on the NHS.

This option allows patients to pay for procedures such as vasectomies or the removal of benign lumps that are not funded by the NHS or are strictly controlled by clinical commissioning groups (CCGs).

The cheapest procedure offered is earwax removal for £160 (€181; $214), while a vasectomy costs £1153 and a total hip replacement costs £8994.

The self funded scheme was launched last month at Care UK’s …
Mutations in Homologous Recombination Genes and Outcomes in Ovarian Carcinoma Patients in GOG 218: An NRG Oncology/Gynecologic Oncology Group Study
Authors: Barbara M. Norquist, Mark F. Brady, Maria I. Harrell, Tom Walsh, Ming K. Lee, Suleyman Gulsuner, Sarah S. Bernards, Silvia Casadei, Robert A. Burger, Krishnansu S. Tewari, Floor Backes, Robert S. Mannel, Gretchen Glaser, Cheryl Bailey, Stephen Rubin, John Soper, Heather A. Lankes, Nilsa C. Ramirez, Mary Claire King, Michael J. Birrer, Elizabeth M. Swisher
Journal: Clinical Cancer Research (2017)

Purpose: We hypothesized that mutations in homologous recombination repair (HRR) genes beyond BRCA1 and BRCA2 improve outcomes for ovarian carcinoma patients treated with platinum therapy and would impact the relative benefit of adding prolonged bevacizumab.Experimental Design: We sequenced DNA from blood and/or neoplasm from 1,195 women enrolled in GOG-0218, a randomized phase III trial in advanced ovarian carcinoma of bevacizumab added to carboplatin and paclitaxel. Defects in HRR were defined as damaging mutations in 16 genes. Proportional hazards models were used to estimate relative hazards for progression-free survival (PFS) and overall survival (OS).Results: Of 1,195 women with ovarian carcinoma, HRR mutations were identified in 307 (25.7%). Adjusted hazards for progression and death compared with those without mutations were lower for women with non-BRCA HRR mutations [HR = 0.73; 95% confidence interval (CI), 0.57-0.94; P = 0.01 for PFS; HR = 0.67; 95% CI, 0.50-0.90; P = 0.007 for OS] and BRCA1 mutations (HR = 0.80; 95% CI, 0.66-0.97; P = 0.02 for PFS; HR = 0.74; 95% CI, 0.59-0.94; P = 0.01 for OS) and were lowest for BRCA2 mutations (HR = 0.52; 95% CI, 0.40-0.67; P < 0.0001 for PFS; HR = 0.36; 95% CI, 0.25-0.53; P < 0.0001 for OS). A test of interaction showed no difference in the effect of bevacizumab on PFS between cases with and without mutations.Conclusions: HRR mutations, including non-BRCA genes, significantly prolong PFS and OS in ovarian carcinoma and should be stratified for in clinical trials. The benefit of adding bevacizumab was not significantly modified by mutation status. Clin Cancer Res; 24(4); 777-83. ©2017 AACR.
Targeting polysialic acid-abundant cancers using oncolytic adenoviruses with fibers fused to active bacteriophage borne endosialidase
Authors: Nikolas T. Martin, Christoph Wrede, Julia Niemann, Jennifer Brooks, David Schwarzer, Florian Kühnel, Rita Gerardy-Schahn
Journal: Biomaterials (2017)

Genetic replacement of adenoviral fiber knobs by ligands that enable tumor specific targeting of oncolytic adenoviruses is challenging because the fiber knob contributes to virus assembly. Here, we present a novel concept by describing stable recombinant adenoviruses with tumor specific infection mode. The fiber knob was replaced by endosialidaseNF (endoNF), the tailspike protein of bacteriophage K1F. EndoNF recognizes polysialic acid, an oncofetal antigen characteristic for high malignant tumors of neuroendocrine origin. An intramolecular chaperone contained in endoNF warrants folding and compensates for the knob function in virus assembly. Obtained recombinant viruses demonstrated polysialic acid dependent infection modes, strong oncolytic capacity with polysialic acid positive cells in culture and a high potential to inhibit tumor growth in a therapeutic mouse model of subcutaneous neuroblastoma. With a single genetic manipulation we achieved ablation of the fiber knob, introduction of a tumor specific ligand, and folding control over the chimeric fiber construct.
Abstract 17836: The Regenerative Capacity of Explant-derived Cardiac Stem Cells Inversely Correlates With Patient Risk for Future Cardiac Events
Authors: Audrey Mayfield, Megan Fitzpatrick, Nicholas Latham, Everad L Tilokee, Melanie Villanueva, Seth Mount, Darryl R Davis
Journal: Circulation (2015)

Background: Although recent trials have demonstrated that cardiac-derived cell products repair damaged myocardium, the influence of age and medical co-morbidities is unknown. Therefore we investigated the effect of medical comorbidities on the functional activity of human explant-derived cardiac stem cells (EDCs). Methods/Results: Human EDCs were cultured from atrial appendages obtained during cardiac surgery. The Long Term Stratification model (LTS) was chosen as the best means of discriminating between patients with few or extensive comorbidities. Increasing LTS score demonstrated a moderate negative correlation with: 1) EDC conditioned media HUVEC tubule formation (R 2 =0.53; r=-4±1, p=0.003), 2) transwell recruitment of circulating angiogenic cells (R 2 =0.48; r=-15±5, p=0.016), 3) decreased echocardiographic ejection fraction (R 2 =0.64, r=-0.7±0.2, p=0.003) and increasing scar burden (R 2 =0.59, r=-0.5±0.2, p=0.04) 3 weeks after myocardial injection of EDCs into a SCID mouse model of myocardial infarction. These effects may be attributable to LTS score dependent decreases in SDF-1 (R 2 =0.33; r=-0.2±0.1, p=0.02) or exosome (R 2 =0.59; r=-2.4±0.8X10 7 , p=0.02) content within conditioned media. Interestingly, the most abundant cytokine in EDC conditioned media (IL-6) demonstrated a positive correlation with increasing LTS scores (R 2 =0.33, r=1.2±0.5, p=0.03). Lentiviral mediated knock down of IL-6 (IL-6KD) by EDCs suggests that IL-6 supports therapeutic regeneration as intra-myocardial injection of IL-6 KD EDCs from low (&lt;3) and high (&gt;5) LTS score patients reduced improvements in ejection fraction by 1.4±0.1 fold (p≤0.05) while increasing scar burden by 1.3±0.1 fold (p≤0.05). Immunohistochemistry demonstrated that IL-6KD reduced newly generated BrdU+ myocytes (p=0.03 vs. scramble treated EDCs) while promoting the persistence of maladaptive myofibroblasts (p=0.01 vs. scramble treated EDCs). Conclusions: The regenerative performance of the earliest cell population cultured from human tissue declines with accumulating medical co-morbidities. This effect is associated with diminished production of pro-cardiogenic cytokines and exosomes while IL-6 plays a novel pivotal role in EDC-mediated repair of damaged myocardium.
Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities
Authors: Kevin J. De France, Fei Xu, Todd Hoare
Journal: Advanced Healthcare Materials (2017)

Abstract Structured macroporous hydrogels that have controllable porosities on both the nanoscale and the microscale offer both the swelling and interfacial properties of bulk hydrogels as well as the transport properties of “hard” macroporous materials. While a variety of techniques such as solvent casting, freeze drying, gas foaming, and phase separation have been developed to fabricate structured macroporous hydrogels, the typically weak mechanics and isotropic pore structures achieved as well as the required use of solvent/additives in the preparation process all limit the potential applications of these materials, particularly in biomedical contexts. This review highlights recent developments in the field of structured macroporous hydrogels aiming to increase network strength, create anisotropy and directionality within the networks, and utilize solvent‐free or additive‐free fabrication methods. Such functional materials are well suited for not only biomedical applications like tissue engineering and drug delivery but also selective filtration, environmental sorption, and the physical templating of secondary networks.
Dark-Blood Delayed Enhancement Cardiac Magnetic Resonance of Myocardial Infarction
Authors: Han W. Kim, Wolfgang G. Rehwald, Elizabeth R. Jenista, David C. Wendell, Peter Filev, Lowie van Assche, Christoph J. Jensen, Michele A. Parker, Enn-ling Chen, Anna Lisa C. Crowley, Igor Klem, Robert M. Judd, Raymond J. Kim
Journal: JACC. Cardiovascular imaging (2017)
Individualized Glycemic Control for U.S. Adults With Type 2 Diabetes
Authors: Neda Laiteerapong, Jennifer M. Cooper, M. Reza Skandari, Philip M. Clarke, Aaron N. Winn, Rochelle N. Naylor, Elbert S. Huang
Journal: Annals of Internal Medicine (2017)

Intensive glycemic control in type 2 diabetes (glycated hemoglobin [HbA1c] level <7%) is an established, cost-effective standard of care. However, guidelines recommend individualizing goals on the basis of age, comorbidity, diabetes duration, and complications.To estimate the cost-effectiveness of individualized control versus uniform intensive control (HbA1c level <7%) for the U.S. population with type 2 diabetes.Patient-level Monte Carlo-based Markov model.National Health and Nutrition Examination Survey 2011-2012.The approximately 17.3 million persons in the United States with diabetes diagnosed at age 30 years or older.Lifetime.Health care sector.Individualized versus uniform intensive glycemic control.Average lifetime costs, life-years, and quality-adjusted life-years (QALYs).Individualized control saved $13 547 per patient compared with uniform intensive control ($105 307 vs. $118 854), primarily due to lower medication costs ($34 521 vs. $48 763). Individualized control decreased life expectancy (20.63 vs. 20.73 years) due to an increase in complications but produced more QALYs (16.68 vs. 16.58) due to fewer hypoglycemic events and fewer medications.Individualized control was cost-saving and generated more QALYs compared with uniform intensive control, except in analyses where the disutility associated with receiving diabetes medications was decreased by at least 60%.The model did not account for effects of early versus later intensive glycemic control.Health policies and clinical programs that encourage an individualized approach to glycemic control for U.S. adults with type 2 diabetes reduce costs and increase quality of life compared with uniform intensive control. Additional research is needed to confirm the risks and benefits of this strategy.National Institute of Diabetes and Digestive and Kidney Diseases.
Case-based discussion from the neonatal intensive care unit: a case of an intentional oesophageal intubation
Authors: Katharine Jamieson, Stephanie Boyd, Susern Tan, Davina Wong, Paul James, Andrew Durward, Andrew Nyman
Journal: Thorax (2017)

Tracheal agenesis (TA) is a rare congenital defect consisting of complete or partial absence of the trachea below the larynx. Antenatal diagnosis is challenging, and most cases are detected in the postnatal period. Airway management of such cases, particularly in the absence of antenatal diagnosis, can be challenging. Various methods of management have been described but with limited success, and overall prognosis remains very poor. We present an unexpected case of TA, highlighting management issues and diagnostic methods.
Does early motor development contribute to speech perception?
Authors: Dawoon Choi, Padmapriya Kandhadai, D. Kyle Danielson, Alison G. Bruderer, Janet F. Werker
Journal: Behavioral and Brain Sciences (2017)

Abstract At the end of the target article, Keven &amp; Akins (K&amp;A) put forward a challenge to the developmental psychology community to consider the development of complex psychological processes – in particular, intermodal infant perception – across different levels of analysis. We take up that challenge and consider the possibility that early emerging stereotypies might help explain the foundations of the link between speech perception and speech production.
Integrative Assessment of Congestion in Heart Failure Throughout the Patient Journey
Authors: Nicolas Girerd, Marie-France Seronde, Stefano Coiro, Tahar Chouihed, Pascal Bilbault, François Braun, David Kenizou, Bruno Maillier, Pierre Nazeyrollas, Gérard Roul, Ludivine Fillieux, William T. Abraham, James Januzzi, Laurent Sebbag, Faiez Zannad, Alexandre Mebazaa, Patrick Rossignol
Journal: JACC Heart Failure (2017)
Abstract 16477: Revascularization After Ischemia is Mediated by Clonally Expanding Endothelial Cells and is Impaired by Aging
Authors: Yosif Manavski, Tina Lucas, Christina Belz, Reinier Boon, Stefanie Dimmeler
Journal: Circulation (2016)

Vascularization is critical to maintain organ function. Outgrowth and clonal expansion of endothelial cells (ECs) has been documented  in vitro , however, the contribution of clonally expanding ECs to physiological versus ischemia-induced vessel growth is unknown. We analyzed the contribution of EC expansion to postnatal retina angiogenesis and ischemia-induced neovascularization after acute myocardial infarction (AMI) as well as hindlimb ischemia (HLI) using so-called Confetti mice that were crossed with the tamoxifen-inducible VE-cadherin Cre-deleter line (CDH5CreERT2/+;Rosa26Confetti/+) for genetic tracing of clonally expanding endothelial cells. Tamoxifen was injected to induce CFP-, GFP-, RFP- and YFP-fluorescent proteins in endothelial cells. In postnatal retina angiogenesis, we observed stochastic EC expansion, resulting in random distribution of fluorescence labeled EC in most sections (less than 10% of sections showed clonal expansion, n=60 sections of 8 mice). However, in pathological angiogenesis during retinopathy of prematurity (ROP) clonally expanded endothelial cells were enriched in 69% of sections (p 9 sections in each group). In aged mice that were subjected to HLI, less clonal expansion events were observed and only 11% of sections showed clonal expansion (p
The end of HIV: Still a very long way to go, but progress continues
Authors: Steven G. Deeks, Sharon R. Lewin, Linda-Gail Bekker
Journal: PLoS Medicine (2017)

In an Editorial accompanying PLOS Medicine's Special Issue on Advances in Prevention, Treatment and Cure of HIV/AIDS, Guest Editors Steven Deeks, Sharon Lewin, and Linda-Gail Bekker discuss priorities in the field and the content of the issue.
Clinical Outcome of 127 Cases of Splanchnic Venous Thrombosis: Benefit of Anticoagulant Therapy
Authors: Lucia Canafoglia, Serena Rupoli, Gianluca Svegliati Baroni, Michele Gironella, Giorgia Micucci, Irene Federici, Massimo Offidani, Alessandro Fiorentini, Alessandra Riva, Lidia Da Lio, Anna Rita Scortechini, Elisa Honorati, Pietro Leoni
Journal: Blood (2016)
Effect of exercise on quality of life (QoL) in 198 older patients with cancer: A URCC NCORP nationwide RCT.
Authors: Kah Poh Loh, Supriya Gupta Mohile, Calvin Cole, Chunkit Fung, Richard Francis Dunne, Po-Ju Lin, Jonathan K. Cho, Alison Katherine Conlin, J. Phillip Kuebler, Karen Michelle Mustian
Journal: Journal of Clinical Oncology (2017)

10019 Background: Cancer and its treatment frequently impact QoL in patients. In older cancer patients, a small decrement in QoL is associated with significant functional impairment, disability, treatment discontinuation and decreased survival. Little is known about the role of exercise in improving QoL in older cancer patients undergoing active chemotherapy and the mechanistic association between inflammation and QoL. We conducted a secondary analysis of a nationwide phase III RCT to assess the effect of exercise on QoL in older cancer patients. Methods: We included 198 older cancer patients (aged ≥60 years) who were randomized to receive chemotherapy alone (C) or with EXCAP (Exercise for Cancer Patients). EXCAP is a home–based progressive aerobic and resistance training program. We used ANCOVA to evaluate the effect of EXCAP on QoL (measured by the Functional Assessment of Cancer Therapy-General, FACT-G, and -Cognitive Function, FACT-Cog). Baseline values, gender and chemotherapy duration were adjusted. We assessed associations between changes in QoL and changes in inflammatory cytokines. Results: Median age was 66.7 ± 2.3 years, 92% were female and 77% had breast cancer. In terms of chemotherapy, 3-week and 2-week regimens were used for 72% and 28%, respectively. EXCAP group had better social (p=0.02), emotional (p=0.04) and physical (p=0.03) well-being post-intervention than the C group. There was also a positive trend for improvement in functional, cognitive and overall well-being (Table 1). In the EXCAP group, improved social well-being was associated with decreases in the pro-inflammatory cytokine, IL-8 (r=0.30, p=0.03). Conclusions: Our analysis showed that exercise improves QoL in older cancer patients receiving active chemotherapy. Improvement in social well-being may be mediated by reducing inflammation. Physicians should consider incorporating exercise when prescribing chemotherapy for older adults with cancer. Clinical trial information: NCT00924651. [Table: see text]