tbuckley/cabot-search huggingface dataset:
2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction
Authors: Clyde W. Yancy, James L. Januzzi, Larry A. Allen, Javed Butler, Leslie L. Davis, Gregg C. Fonarow, Nasrien E. Ibrahim, Mariell Jessup, JoAnn Lindenfeld, Thomas M. Maddox, Frederick A. Masoudi, Shweta R. Motiwala, J. Herbert Patterson, Mary Norine Walsh, Alan Wasserman
Journal: Journal of the American College of Cardiology (2017)
Abstract 13054: Perfect 1 Year Angiographic Patency of in vivo Tissue-Engineered Vascular Grafts With an Ultra Small Diameter of 0.6 mm (MicroBiotubes) in a Rat Model
Authors: Daizo Ishii, Jun-Ichiro Enmi, Hidehiro Iida, Kaoru Kurisu, Yasuhide Nakayama
Journal: Circulation (2016)

Background and Purpose: Biotubes are autologous tubular connective tissues formed by in-body tissue architecture technology, which is a novel and practical approach in regenerative medicine. We confirmed that Microbiotubes (MBs) with diameter of 0.6 mm had high performance potential as a reliable arterial graft in acute phase of implantation in a rat model. In this study, quality and patency of MBs in chronic phase were evaluated by histological or magnetic resonance angiographic (MRA) examinations, respectively. Method: The mold for multiple preparing of MBs was assembled by several stainless wires covered with silicone tubes. The molds were surgically embedded into the dorsal subcutaneous pouches of rats. After 2 months, the molds were harvested with surrounding tissues and MBs were obtained by removing the molds. MBs (length, 10 mm; internal diameter, 0.6 mm) were implanted in rat femoral arteries (diameter, ca. 0.5 mm) in allogenic manner by end-to-end anastomosis without use of any anticoagulant agents. Ten patent MBs after 1-month implantation were observed by follow-up 7- Tesla MRA until 1 year after implantation. Results: In all follow-up periods, all MBs were patent without any observable stenoses or dilatations and a difference of signal intensity between MBs and native artery was obscure (Fig. 1). Moreover, native-like reconstructed structure of MBs’ wall was conserved histologically for 1 year. Conclusion: It was unprecedented result that there was no occluded case in chronic phase and MBs preserved high quality and patency for a long-term period. We are convinced that MBs could be useful grafts for ultramicrosurgery, such as a replantation of severed fingers or a reconstruction of lymphatic vesssels, in the not too distant future.
Phase I Dose-Escalation Trial of PT2385, a First-in-Class Hypoxia-Inducible Factor-2α Antagonist in Patients With Previously Treated Advanced Clear Cell Renal Cell Carcinoma
Authors: Kevin D. Courtney, Jeffrey R. Infante, Elaine T. Lam, Robert A. Figlin, Brian I. Rini, James Brugarolas, Naseem J. Zojwalla, Ann M. Lowe, Keshi Wang, Eli M. Wallace, John A. Josey, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2017)

Purpose The von Hippel-Lindau tumor suppressor is inactivated in the majority of clear cell renal cell carcinomas (ccRCCs), leading to inappropriate stabilization of hypoxia-inducible factor-2α (HIF-2α). PT2385 is a first-in-class HIF-2α antagonist. Objectives of this first-in-human study were to characterize the safety, pharmacokinetics, pharmacodynamics, and efficacy, and to identify the recommended phase II dose (RP2D) of PT2385. Patients and Methods Eligible patients had locally advanced or metastatic ccRCC that had progressed during one or more prior regimens that included a vascular endothelial growth factor inhibitor. PT2385 was administered orally at twice-per-day doses of 100 to 1,800 mg, according to a 3 + 3 dose-escalation design, followed by an expansion phase at the RP2D. Results The dose-escalation and expansion phases enrolled 26 and 25 patients, respectively. Patients were heavily pretreated, with a median of four (range, one to seven) prior therapies. No dose-limiting toxicity was observed at any dose. On the basis of safety, pharmacokinetic, and pharmacodynamic profiling, the RP2D was defined as 800 mg twice per day. PT2385 was well tolerated, with anemia (grade 1 to 2, 35%; grade 3, 10%), peripheral edema (grade 1 to 2, 37%; grade 3, 2%), and fatigue (grade 1 to 2, 37%; no grade 3 or 4) being the most common treatment-emergent adverse events. No patients discontinued treatment because of adverse events. Complete response, partial response, and stable disease as best response were achieved by 2%, 12%, and 52% of patients, respectively. At data cutoff, eight patients remained in the study, with 13 patients in the study for ≥ 1 year. Conclusion PT2385 has a favorable safety profile and is active in patients with heavily pretreated ccRCC, validating direct HIF-2α antagonism for the treatment of patients with ccRCC.
Hépatite aiguë C chez les homosexuels masculins atteints par le VIH, Paris, France, 2001-2004
Authors: L Gambotti
Journal: Eurosurveillance (2005)

En 2004, trois services hospitaliers parisiens ont signale a l’Institut de veille sanitaire des cas recents d’hepatite aigue C chez des homosexuels masculins (HM) atteints par le VIH (VIH+) pour lesquels les modes habituels de transmission du virus de l’h...
Letter by Jin-Shan and Xue-Bin Regarding Article, “Out-of-Hospital Cardiac Arrest: An Underlying Reversible Cause”
Authors: He Jin-Shan, Li Xue-Bin
Journal: Circulation (2017)

We read with great interest the case presented by Robert and colleagues 1 about pulseless electric activity (PEA) that shows the importance of interpreting the ECG and finding the cause of PEA in cardiopulmonary resuscitation.We have 2 questions about this case.First, PEA can be the result of a wide spectrum of potential causes, including significant hypoxia, profound acidosis, severe hypovolemia, tension pneumothorax, electrolyte imbalance, drug overdose, sepsis, large myocardial infarction, massive pulmonary embolism, cardiac tamponade, hypoglycemia, hypothermia, and trauma. 2 PEA is defined as myocardial electric activity without associated mechanical activity and can be classified as pseudo-PEA and true PEA. 3 Pseudo-PEA is a profound state of cardiogenic shock that is inadequate to maintain perfusion pressure and thus a nondetectable pulse.As for the patient in this case, his heart can still contract normally, but as a result of the compression of pneumothorax, there is not enough blood returning back to the left ventricle and being pumped out.Is this pseudo-PEA instead of true PEA?Second, pseudo-PEA rhythms are often narrow QRS complex tachycardias; true PEAs are usually seen at a slow ventricular rate with a wide QRS complex.This patient's ECG reveals a rhythm that is not strictly regular, without a visible P wave, and with a frequency of 60 bpm and a QRS interval of 150 milliseconds.Why is his electrocardiographic performance in accordance with true PEA but he is classified as pseudo-PEA?We hope to learn more about this case from your answers.
Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate
Authors: Robin Rajan, Manoj K. Sabnani, Vikram Mavinkurve, Hilary Shmeeda, Hossein Mansouri, Sandrine Bonkoungou, Alexander D. Le, Laurence M. Wood, Alberto A. Gabizon, Ninh M. La-Beck
Journal: Journal of Controlled Release (2017)

Liposomal nanoparticles are the most commonly used drug nano-delivery platforms. However, recent reports show that certain pegylated liposomal nanoparticles (PLNs) and polymeric nanoparticles have the potential to enhance tumor growth and inhibit antitumor immunity in murine cancer models. We sought herein to identify the mechanisms and determine whether PLN-associated immunosuppression and tumor growth can be reversed using alendronate, an immune modulatory drug. By conducting in vivo and ex vivo experiments with the immunocompetent TC-1 murine tumor model, we found that macrophages were the primary cells that internalized PLN in the tumor microenvironment and that PLN-induced tumor growth was dependent on macrophages. Treatment with PLN increased immunosuppression as evidenced by increased expression of arginase-1 in CD11b+ Gr1+ cells, diminished M1 functionality in macrophages, and globally suppressed T-cell cytokine production. Encapsulating alendronate in PLN reversed these effects on myeloid cells and shifted the profile of multi-cytokine producing T-cells towards an IFNγ+ perforin+ response, suggesting increased cytotoxic functionality. Importantly, we also found that PLN-encapsulated alendronate (PLN-alen), but not free alendronate, abrogated PLN-induced tumor growth and increased progression-free survival. In summary, we have identified a novel mechanism of PLN-induced tumor growth through macrophage polarization and immunosuppression that can be targeted and inactivated to improve the anticancer efficacy of PLN-delivered drugs. Importantly, we also determined that PLN-alen not only reversed protumoral effects of the PLN carrier, but also had moderate antitumor activity. Our findings strongly support the inclusion of immune-responsive tumor models and in-depth immune functional studies in the preclinical drug development paradigm for cancer nanomedicines, and the further development of chemo-immunotherapy strategies to co-deliver alendronate and chemotherapy for the treatment of cancer.
Gamification Shows Promise in Motivating Physical Activity
Authors: Anita Slomski
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Biomimetic nanoparticles for inflammation targeting
Authors: Kai Jin, Zimiao Luo, Bo Zhang, Zhiqing Pang
Journal: Acta Pharmaceutica Sinica B (2017)

There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels, and molecular mediators directed against harmful stimuli, is closely associated with many human diseases. As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.
Serum chemokine CXCL7 activity after resection of breast cancer.
Authors: Mary Ann Kosir, Donghong Ju
Journal: Journal of Clinical Oncology (2013)

e22182 Background: The chemokine CXCL7 is associated with tumor migration, invasion and angiogenesis and is a ligand for CXCR2. The purpose of the study is to measure changes in serum chemokine CXCL7 from resectable breast cancer patients between preoperative and postoperative blood samples. Methods: With IRB approval, we prospectively collected serum samples from patients undergoing breast cancer surgery immediately preoperatively and at least one week postoperatively. Serum CXCL7 protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA) using human CXCL7/NAP-2 Duo set ELISA Development System (R and D Systems, Minneapolis, MN) according to manufacturer’s instructions. Measurements were performed in duplicate with three separate experiments. Results were analyzed using unpaired and paired Student’s t-Test. Demographic and clinical information were collected. Normal donor samples were from ProteoGenex. Results: Twenty-three matched serum samples were analyzed. The mean age was 52 years (range 36-67), 65.2% were African American, 56.5% underwent partial mastectomy. There were 5 in Stage I, 9 in Stage II, 2 in Stage III, and 7 in Stage 0. Only 4 of 16 with invasive cancer had nodal disease, 11 were ER positive, 6 were triple negative, and 5 of 7 with DCIS were ER positive. Matched serum samples showed greater CXCL7 serum levels in preoperative samples when compared to normal donor samples (9.10 ±0.45 vs 8.10 ± 0.22 ug/ml; mean±sem, p&lt;0.05). The CXCL7 serum levels were significantly decreased in postoperative serum as compared to preoperative serum (8.40 ± 0.47 vs 9.10 ± 0.45 ug/ml; mean±sem, p&lt;0.05) reaching normal donor serum levels. When individual matched pairs of serum were analyzed, 16 showed decrease in postoperative CXCL7 levels compared to preoperative. Conclusions: The chemokine CXCL7 found in serum is increased in breast cancer patients compared to normal donors, and significantly decreases postoperatively to normal levels. This supports translational research of the role of CXCL7 in breast cancer.
Association of Preoperative and Postoperative Serum Carcinoembryonic Antigen and Colon Cancer Outcome
Authors: Tsuyoshi Konishi, Yoshifumi Shimada, Meier Hsu, Lauren Tufts, Rosa Jimenez-Rodriguez, Andrea Cercek, Rona Yaeger, Leonard Saltz, J. Joshua Smith, Garrett M. Nash, José G. Guillem, Philip B. Paty, Julio Garcia-Aguilar, Mithat Gonen, Martin R. Weiser
Journal: JAMA Oncology (2017)

Guidelines recommend measuring preoperative carcinoembryonic antigen (CEA) in patients with colon cancer. Although persistently elevated CEA after surgery has been associated with increased risk for metastatic disease, prognostic significance of elevated preoperative CEA that normalized after resection is unknown.To investigate whether patients with elevated preoperative CEA that normalizes after colon cancer resection have a higher risk of recurrence than patients with normal preoperative CEA.This retrospective cohort analysis was conducted at a comprehensive cancer center. Consecutive patients with colon cancer who underwent curative resection for stage I to III colon adenocarcinoma at the center from January 2007 to December 2014 were identified.Patients were grouped into 3 cohorts: normal preoperative CEA, elevated preoperative but normalized postoperative CEA, and elevated preoperative and postoperative CEA.Three-year recurrence-free survival (RFS) and hazard function curves over time were analyzed.A total of 1027 patients (461 [50.4%] male; median [IQR] age, 64 [53-75] years) were identified. Patients with normal preoperative CEA had 7.4% higher 3-year RFS (n = 715 [89.7%]) than the combined cohorts with elevated preoperative CEA (n = 312 [82.3%]) (P = .01) but had RFS similar to that of patients with normalized postoperative CEA (n = 142 [87.9%]) (P = .86). Patients with elevated postoperative CEA had 14.9% lower RFS (n = 57 [74.5%]) than the combined cohorts with normal postoperative CEA (n = 857 [89.4%]) (P = .001). The hazard function of recurrence for elevated postoperative CEA peaked earlier than for the other cohorts. Multivariate analyses confirmed that elevated postoperative CEA (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5), but not normalized postoperative CEA (HR, 0.77; 95% CI, 0.45-1.30), was independently associated with shorter RFS.Elevated preoperative CEA that normalizes after resection is not an indicator of poor prognosis. Routine measurement of postoperative, rather than preoperative, CEA is warranted. Patients with elevated postoperative CEA are at increased risk for recurrence, especially within the first 12 months after surgery.
DotAligner: identification and clustering of RNA structure motifs
Authors: Martin A. Smith, Stefan E. Seemann, Xiu Cheng Quek, John S. Mattick
Journal: Genome biology (2017)

The diversity of processed transcripts in eukaryotic genomes poses a challenge for the classification of their biological functions. Sparse sequence conservation in non-coding sequences and the unreliable nature of RNA structure predictions further exacerbate this conundrum. Here, we describe a computational method, DotAligner, for the unsupervised discovery and classification of homologous RNA structure motifs from a set of sequences of interest. Our approach outperforms comparable algorithms at clustering known RNA structure families, both in speed and accuracy. It identifies clusters of known and novel structure motifs from ENCODE immunoprecipitation data for 44 RNA-binding proteins.
Hormone Therapy–Related Hot Flashes and Their Management
Authors: Arjun Gupta
Journal: JAMA Oncology (2017)

Hormone Therapy-Related Hot Flashes and Their ManagementHormone therapy for cancer may be associated with hot flashes in some patients.What Is Hormone Therapy?Certain cancers, such as some subtypes of breast and prostate cancer, are dependent on sex hormones for growth.Reducing the level and activity of sex hormones is one strategy used to treat them.This is achieved through surgical removal of the ovaries or testes, or more commonly through the administration of certain drugs.By depriving cancers of sex hormones, these drugs act as antihormones, but this treatment is nonetheless called hormone therapy.This hormone therapy is different from the more commonly prescribed hormone therapy used to treat symptoms of menopause.
Long-term proton pump inhibitor use is a risk factor of gastric cancer after treatment for <i>Helicobacter pylori</i> : a retrospective cohort analysis
Authors: Ryota Niikura, Yoku Hayakawa, Yoshihiro Hirata, Atsuo Yamada, Mitsuhiro Fujishiro, Kazuhiko Koike
Journal: Gut (2017)

We read with interest the recent publication by Cheung et al . The authors conclude that proton pump inhibitor (PPI) use is associated with a 2.4-fold increase in the risk of gastric cancer in patients who received Helicobacter pylori eradication therapy.1 This is an important finding given that the safety of long-term PPI use remains unclear. Notably, no significant association between histamine-2 receptor antagonist (H2RA) use and gastric cancer was observed, which suggests a PPI-specific effect in this context.

Cheung et al used a large population-based database to select patients after eradication and performed propensity score adjustment analysis. However, as the authors described in the Discussion section, we have concerns about the limitations of this study, in particular the lack of endoscopic and histological examinations, the results of which could influence the association between PPI use and gastric cancer. The presence …
A phase I dose expansion cohort study of dasatinib in combination with bevacizumab in advanced solid tumors (NCT01445509).
Authors: Akosua Osei-Tutu, Ana Tablante Nunes, Jung-min Lee, Minshu Yu, Lidia Hernandez, Helen X. Chen, Naoko Takebe, Nicole D. Houston, Irene Ekwede, Seth M. Steinberg, Jin-Qiu Chen, Liang Cao, W. Douglas Figg, Donna Butcher, Christina M. Annunziata, Elise C. Kohn
Journal: Journal of Clinical Oncology (2017)

2585 Background: Dasatinib is a known inhibitor of the SRC family kinases and is approved for use in chronic myelogenous leukemia. Bevacizumab inhibits angiogenesis, binding to human vascular endothelial growth factor (VEGF, or VEGF-A) with high affinity. VEGF receptor signals intracellularly via a cascade regulated by SRC. Given the presence of this signaling pathway in both tumor cells and endothelial cells, we hypothesized that attenuation of both SRC and VEGF simultaneously would have synergistic antitumor activity. We previously reported the maximum tolerated dose (MTD) of dasatinib 100mg daily with bevacizumab 10mg/kg q2wk in patients with advanced solid tumors. We now report clinical activity of the combination, and translational endpoints of an expansion cohort. Methods: This is a phase 1 dose escalation with non-randomized expansion cohort. We monitored safety, and response was assessed every 8 weeks using RECIST criteria. Correlative endpoints include blood flow by dynamic MR imaging, endothelial cell density by CD31 immunohistochemistry, functional angiogenic potential by plasma cytokines and rat aortic ring assay, and tumor cell activation state by phosphoprotein analysis. Results: We enrolled 39 patients at the MTD for a total of 50 patients on study, including both the dose escalation and dose expansion phases. No patient experienced dose limiting toxicities during dose escalation. The most common adverse events were grade 2 hypertension and proteinuria. By RECIST, 5 (10%) patients had a partial response, and stable disease was seen in 29 (58%) of patients with a range from 12-145+ weeks on study. We had two exceptional responders with endometrial carcinoma who continue on study to date (112 weeks and 145 weeks). Translational endpoints were correlated with clinical outcome. Conclusions: Bevacizumab and dasatinib are safe in combination, with potential clinical activity. This combination warrants further investigation in solid tumors. Ongoing translational research using specimens from exceptional responders will suggest potential biomarkers of clinical benefit, to be tested in future prospective clinical trials. Clinical trial information: NCT01445509.
THU0258 Meloxicam does not increase the risk of acute myocardial infarction, congestive heart failure, oedema or hypertension compared to nsaids: results from a pooled analysis of 27,039 patients
Authors: G Singh
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Meloxicam is a novel NSAID that has been widely used in &gt;100 countries with &gt; 40 million prescriptions over the last 6 years. Meloxicam has been shown in numerous clinical trials to be effective, and to have lower rates of gastrointestinal adverse events than other NSAIDs such as diclofenac, piroxicam and naproxen. However, the renal and cardiovascular toxicity of meloxicam has not been extensively studied before. This is an important clinical issue because recent studies have raised considerable concern about cardiovascular and renal safety profile of some new Cox-2 selective NSAIDs. <h3>Objectives</h3> To document the risk of acute myocardial infarction, congestive heart failure, oedema and hypertension in patients taking 7.5–30 mg doses of meloxicam, and traditional NSAIDs (diclofenac 100–150 mg, naproxen 500–750 mg, piroxicam 20 mg) in a pooled analysis of 27,039 patients. <h3>Methods</h3> We pooled data from all Meloxicam clinical trials that were at least 3 weeks in duration and included at least 20 patients per arm. Thirty-five trials with 27,039 patients on Meloxicam, comparator NSAID?s, or placebo were included in the analysis. Nearly 39% (8109) patients were over age 65. Since trials were of varying durations, we report event rates as incidence per 100 patient-years of exposure. <h3>Results</h3> Of the 27,039 patients studied, 15,071 received meloxicam in doses of 7.5 ? 30 mg daily. A total of 11,078 patients took diclofenac, naproxen or piroxicam. An additional 736 patients were randomised to placebo. The number of patients with cardiovascular and renal events adverse events is shown in the Table 1 below. Incidence rates in parenthesis refer to rates per 100 patient years. <h3>Conclusion</h3> Meloxicam in doses of 7.5–30 mg is not associated with increased incidence of cardiovascular or renal toxicity.
Targeting superoxide dismutase to endothelial caveolae profoundly alleviates inflammation caused by endotoxin
Authors: Vladimir V. Shuvaev, Raisa Yu. Kiseleva, Evguenia Arguiri, Carlos H. Villa, Silvia Muro, Melpo Christofidou-Solomidou, Radu V. Stan, Vladimir R. Muzykantov
Journal: Journal of Controlled Release (2017)