tbuckley/cabot-search huggingface dataset:
Therapeutic Fluorescent Hybrid Nanoparticles for Traceable Delivery of Glucocorticoids to Inflammatory Sites
Authors: Joanna Napp, M. Andrea Markus, Joachim G. Heck, Christian Dullin, Wiebke Möbius, Dimitris Gorpas, Claus Feldmann, Frauke Alves
Journal: Theranostics (2018)

Treatment of inflammatory disorders with glucocorticoids (GCs) is often accompanied by severe adverse effects.Application of GCs via nanoparticles (NPs), especially those using simple formulations, could possibly improve their delivery to sites of inflammation and therefore their efficacy, minimising the required dose and thus reducing side effects.Here, we present the evaluation of NPs composed of GC betamethasone phosphate (BMP) and the fluorescent dye DY-647 (BMP-IOH-NPs) for improved treatment of inflammation with simultaneous in vivo monitoring of NP delivery.Methods: BMP-IOH-NP uptake by MH-S macrophages was analysed by fluorescence and electron microscopy.Lipopolysaccharide (LPS)-stimulated cells were treated for 48 h with BMP-IOH-NPs (1×10 -5 -1×10 -9 M), BMP or dexamethasone (Dexa).Drug efficacy was assessed by measurement of interleukin 6. Mice with Zymosan-A-induced paw inflammation were intraperitoneally treated with BMP-IOH-NPs (10 mg/kg) and mice with ovalbumin (OVA)-induced allergic airway inflammation (AAI) were treated intranasally with BMP-IOH-NPs, BMP or Dexa (each 2.5 mg/kg).Efficacy was assessed in vivo by paw volume measurements with µCT and ex vivo by measurement of paw weight for Zymosan-A-treated mice, or in the AAI model by in vivo x-ray-based lung function assessment and by cell counts in the bronchoalveolar lavage (BAL) fluid and histology.Delivery of BMP-IOH-NPs to the lungs of AAI mice was monitored by in vivo optical imaging and by fluorescence microscopy.Results: Uptake of BMP-IOH-NPs by MH-S cells was observed during the first 10 min of incubation, with the NP load increasing over time.The anti-inflammatory effect of BMP-IOH-NPs in vitro was dose dependent and higher than that of Dexa or free BMP, confirming efficient release of the drug.In vivo, Zymosan-A-induced paw inflammation was significantly reduced in mice treated with BMP-IOH-NPs.AAI mice that received BMP-IOH-NPs or Dexa but not BMP revealed significantly decreased eosinophil numbers in BALs and reduced immune cell infiltration in lungs.Correspondingly, lung function parameters, which were strongly affected in non-treated AAI mice, were unaffected in AAI mice treated with BMP-IOH-NPs and resembled those of healthy animals.Accumulation of BMP-IOH-NPs within the lungs of AAI mice was detectable by optical imaging for at least 4 h in vivo, where they were preferentially taken up by peribronchial and alveolar M2 macrophages. Conclusion:Our results show that BMP-IOH-NPs can effectively be applied in therapy of inflammatory diseases with at least equal efficacy as the gold standard Dexa, while their delivery can be simultaneously tracked in vivo by fluorescence imaging.BMP-IOH-NPs thus have the potential to reach clinical applications.
Association of Conflicts of Interest for Public Speakers for the Peripheral and Central Nervous System Drugs Advisory Committee of the US Food and Drug Administration With Their Statements
Authors: Wade Arthur, Jennifer Austin, Cole Wayant, Matt Vassar
Journal: JAMA Neurology (2018)

This study uses transcripts from the Peripheral and Central Nervous System Drug Advisory Committee of the US Food and Drug Administration to evaluate the association of conflicts of interest for public speakers at committee meetings with the speakers' statements.
Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome
Authors: Martin Laclaustra, Belen Moreno-Franco, Jose Manuel Lou-Bonafonte, Rocio Mateo-Gallego, Jose Antonio Casasnovas, Pilar Guallar-Castillon, Ana Cenarro, Fernando Civeira
Journal: Diabetes Care (2018)

OBJECTIVE Diabetes prevalence and incidence increase among individuals with hypothyroidism but also among those with hyperthyroxinemia, which seems contradictory. Both high free thyroxine (fT4) and high thyroid-stimulating hormone (TSH) are present in the resistance to thyroid hormone syndrome. A mild acquired resistance to thyroid hormone might occur in the general population and be associated with diabetes. We aimed to analyze the association of resistance to thyroid hormone indices (the Thyroid Feedback Quantile-based Index [TFQI], proposed in this work, and the previously used Thyrotroph T4 Resistance Index and TSH Index) with diabetes. RESEARCH DESIGN AND METHODS We calculated the aforementioned resistance to thyroid hormone indices based on a U.S. representative sample of 5,129 individuals ≥20 years of age participating in the 2007–2008 National Health and Nutrition Examination Survey (NHANES). Also, to approximate TFQI, a U.S.-referenced Parametric TFQI (PTFQI) can be calculated with the spreadsheet formula =NORM.DIST(fT4_cell_in_pmol_per_L,10.075,2.155,TRUE)+NORM.DIST(LN(TSH_cell_in_mIU_per_L),0.4654,0.7744,TRUE)−1. Outcomes of interest were glycohemoglobin ≥6.5%, diabetes medication, diabetes-related deaths (diabetes as contributing cause of death), and additionally, in a fasting subsample, diabetes and metabolic syndrome. Logistic and Poisson regressions were adjusted for sex, age, and race/ethnicity. RESULTS Odd ratios for the fourth versus the first quartile of TFQI were 1.73 (95% CI 1.32, 2.27) (Ptrend = 0.002) for positive glycohemoglobin and 1.66 (95% CI 1.31, 2.10) (Ptrend = 0.001) for medication. Diabetes-related death rate ratio for TFQI being above versus below the median was 4.81 (95% CI 1.01, 22.94) (Ptrend = 0.015). Further adjustment for BMI and restriction to normothyroid individuals yielded similar results. Per 1 SD in TFQI, odds increased 1.13 (95% CI 1.02, 1.25) for diabetes and 1.16 (95% CI 1.02, 1.31) for metabolic syndrome. The other resistance to thyroid hormone indices showed similar associations for diabetes-related deaths and metabolic syndrome. CONCLUSIONS Higher values in resistance to thyroid hormone indices are associated with obesity, metabolic syndrome, diabetes, and diabetes-related mortality. Resistance to thyroid hormone may reflect energy balance problems driving type 2 diabetes. These indices may facilitate monitoring treatments focused on energy balance.
Abstract P074: Smoking Status and Incidence of Cancer After Myocardial Infarction: a 20-year Follow-up Study
Authors: Yariv Gerber, Katrin Lotan, Uri Goldbourt
Journal: Circulation (2017)

Objectives: We compared cancer incidence after acute myocardial infarction (MI) of never smokers, pre-MI quitters, post-MI quitters and persistent smokers, and assessed whether cigarette reduction among continued smokers is associated with lower cancer risk. Methods: Consecutive patients aged ≤65 years discharged from 8 hospitals in central Israel after first MI in 1992-3 were followed for cancer through 2013. Extensive data, including self-reported smoking habits, were obtained at the index hospitalization and 4 times during follow-up. Cox proportional hazards and Fine &amp; Gray competing risks models were constructed to assess the hazard ratios (HRs) for cancer associated with baseline smoking categories. Smoking categories were also modeled as time-varying variables using extended Cox models. Results: Overall, 1,486 cancer-free participants at baseline were studies (mean±SD age, 54±8 years; 81% male). Smokers were younger than nonsmokers and more likely to be male and of lower socioeconomic status. Over a median follow-up of 21.4 years, 273 incident cancers were diagnosed. Baseline smoking was associated with ~40% increased risk of cancer; ~25% after accounting for death as a competing event. Taking changes in smoking during follow-up into account, the increased risk was largely confined to persistent smokers, whereas the risk in post-MI quitters was close to that of never smokers (Figure). Among patients who continued smoking after MI, each reduction of 10 cigarettes relative to pre-MI consumption was associated with an adjusted HR of 0.86 (95% CI: 0.74-1.00). Conclusions: Smoking cessation either before or after MI is associated with lower risk of cancer. Reducing consumption among persistent smokers appears also to be beneficial.
Evaluation and Significance of CD25 Expression in Hematopoietic Stem/Progenitor Cell Fraction of Bone Marrow Cells in Chronic Myelogenous Leukemia Patients
Authors: Hidenori Kasahara, Daiki Karigane, Rie Yamazaki, Shinya Fujita, Kouhei Shirosita, Masatoshi Sakurai, Yuya Koda, Taku Kikuchi, Jun Kato, Takayuki Shimizu, Takehiko Mori, Yoko Yatabe, Tomoko Arai, Mitsuru Murata, Hiroshi Kobayashi, Keiyo Takubo, Shinichiro Okamoto
Journal: Blood (2018)
OA04 Factors Influencing the Non-Administration of Chemotherapies in Patients Who Progressed After First-Line EGFR-TKIs
Authors: T. Mizuno, H. Horinouchi, S. Watanabe, J. Sato, R. Morita, Y. Matsumoto, S. Murakami, Y. Goto, S. Kanda, Y. Fujiwara, N. Yamamoto, Y. Ohe
Journal: Journal of Thoracic Oncology (2018)
Validation of the Hepatocellular Carcinoma Early Detection Screening (HES) Algorithm in a Cohort of Veterans With Cirrhosis
Authors: Nabihah Tayob, Israel Christie, Peter Richardson, Ziding Feng, Donna L. White, Jessica Davila, Douglas A. Corley, Fasiha Kanwal, Hashem B. El-Serag
Journal: Clinical Gastroenterology and Hepatology (2018)
Virtual TEVAR: Overcoming the Roadblocks of In-Silico Tools for Aortic Dissection Treatment
Authors: Vanessa Diaz-Zuccarini, Mirko Bonfanti, Gaia Franzetti, Stavroula Balabani
Journal: Theranostics (2018)

The use of in silico tools for the interventional planning of complex vascular conditions, such as Aortic Dissections has been often limited by high computational cost, involving long timescales for accurate results to be produced and low numbers of patients, precluding the use of statistical analyses to inform individual-level models.In the paper [
Dissolvable Stents: 3D‐Printed Sugar‐Based Stents Facilitating Vascular Anastomosis (Adv. Healthcare Mater. 24/2018)
Authors: Ali Farzin, Amir K. Miri, Fatemeh Sharifi, Negar Faramarzi, Arian Jaberi, Azadeh Mostafavi, Ricky Solorzano, Yu Shrike Zhang, Nasim Annabi, Ali Khademhosseini, Ali Tamayol
Journal: Advanced Healthcare Materials (2018)

In article number 1800702 by Ali Khademhosseini and Ali Tamayol, sugar-based stents are developed that can facilitate vascular anastomosis. The stents can hold the vessels in place during surgical procedures and degrade quickly in the blood flow without inducing thrombosis.
ALLO-819, an Allogeneic Flt3 CAR T Therapy Possessing an Off-Switch for the Treatment of Acute Myeloid Leukemia
Authors: Cesar Sommer, Ivana Djuretic, Julien Valton, Duy Nguyen, Janette Sutton, Kris Poulsen, Julianne Smith, Ivana Djuretic, Javier Chaparro-Riggers, Barbra Sasu
Journal: Blood (2018)
Helping Pregnant Women and Clinicians Understand the Risk of Ondansetron for Nausea and Vomiting During Pregnancy
Authors: David M. Haas
Journal: JAMA (2018)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Recurrence of periocular basal cell carcinoma and squamous cell carcinoma after Mohs micrographic surgery: a retrospective cohort study
Authors: F. Weesie, N.C. Naus, D. Vasilic, L.M. Hollestein, R.R. van den Bos, M. Wakkee
Journal: British Journal of Dermatology (2018)

Despite the widespread use of Mohs micrographic surgery (MMS) for periocular basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) - together called keratinocyte carcinoma (KC) - follow-up data regarding recurrences are limited.To investigate the recurrence rate for periocular KCs after MMS and to describe our experience with interdisciplinary collaborations.Patients with periocular KCs treated with MMS between 2006 and 2016 in a tertiary MMS referral hospital were included in this retrospective cohort study. Descriptive statistics were used to describe the MMS procedure-related characteristics. Using follow-up data from the electronic patient records and linkage with the Dutch nationwide network and registry of histopathology and cytopathology on 30 June 2017, the recurrence rate was evaluated and calculated using a cumulative incidence curve.In total, 683 (93·7%) periocular BCCs and 46 (6·3%) SCCs were treated with MMS. Three-quarters (n = 549) were primary tumours and the majority were located at the medial canthus or lower eyelid (n = 649, 89·0%). In 505 MMS procedures (69·3%) an oculoplastic surgeon participated, and in 63 patients (8·6%) a plastic surgeon performed the reconstruction. After a median follow-up of 46 months the recurrence rate was 3·0%, based on 22 recurrences (20 BCCs and two SCCs).MMS is an excellent treatment option for periocular KCs, with a low recurrence rate. Due to this specific anatomical location an interdisciplinary approach should pre-eminently be considered.
Microbiota-Induced TNF-like Ligand 1A Drives Group 3 Innate Lymphoid Cell-Mediated Barrier Protection and Intestinal T Cell Activation during Colitis
Authors: Jim G. Castellanos, Viola Woo, Monica Viladomiu, Gregory Putzel, Svetlana Lima, Gretchen E. Diehl, Andrew R. Marderstein, Jorge Gandara, Alexendar R. Perez, David R. Withers, Stephan R. Targan, David Q. Shih, Ellen J. Scherl, Randy S. Longman
Journal: Immunity (2018)
Sixty seconds on . . . Apple ECG
Authors: Owen Dyer
Journal: BMJ (2018)

It’s a watch, but not as you know it. Apple Watch Series 4 monitors heart rate and can create an ECG from your finger. So you could, in theory, take one when you have chest pain and show it to your doctor later. It can also detect atrial fibrillation.

At detecting atrial fibrillation, yes. What little data are available suggest that it generates …
First-line systemic real-world treatment of patients with advanced/metastatic NSCLC in the UK
Authors: M. Wang, P. Dhokia, S. Menon, B. Martindale
Journal: Annals of Oncology (2018)

Background: Immuno-oncology (IO) has changed treatment (Tx) landscape of non-small cell lung cancer (NSCLC). IO is efficacious and a less toxic alternative to standard chemotherapy in treating NSCLC. This study analysed 1st line (1L) Tx patterns of patients with stage IIIb/IV NSCLC in real-world setting. Methods: IQVIA Oncology Dynamics (OD) database was used to identify stage IIIb/IV NSCLC patients who initiated and received 1L Tx between June 2017 and March 2018 in the UK. IQVIA OD is a syndicated database collecting longitudinal, anonymized, patient-level oncology data through a quarterly physician panel survey. The UK panel characteristics were: 94% public, 65% university, 12% Scotland/Northern Ireland - 6% Wales - 82% England. The response rate ranged 13-72% among circa 225 physicians per quarterly pulse. Data on patient/disease characteristics, Tx, and biomarkers were extracted and analysed. Results: In total, data from 738 stage IIIb/IV NSCLC patients receiving 1L cancer Tx were analysed. At questionnaire completion, 57% of patients were male and 68% were aged >60 years. Most patients had cancers with non-squamous histology (79%); fewer had squamous (20%) and other (1%). ECOG performance status was assessed as 0 in 14% and 1 in 76% of patients, and metastases were mostly found in the lung (49%), bone and liver (34% each), lymph nodes local (36%) and distant (25%). COPD was the most common comorbidity (28%); 40% of patients reported none. 49% were former smokers and 22% current smokers. Chemotherapy and targeted therapies were the most frequent 1L Tx received by 301 (41%) and 219 (30%) patients, respectively. 30% of patients (n = 218) received IO Tx in 1L; pembrolizumab was the most common IO therapy (n = 216, 29%). PD-L1 testing was performed among 76% of the latest quarter patients (n = 195/255); 106 (54%) were positive (PD-L1+; ≥50%), 82 (42%) negative (PD-L1-; <50%) and 7 awaiting results. Most PD-L1+ patients received pembrolizumab in 1L (86%), whereas PD-L1- patients were mostly treated with chemotherapy (73%) and one third received targeted therapies. Conclusions: In the current UK treatment landscape for stage IIIb/IV NSCLC, only 30% of patients were treated with IO Tx in 1L. A high proportion of 1L patients is still treated with traditional chemotherapy. Editorial acknowledgement: Editorial assitance was provided by Eleonora Morais from IQVIA. Legal entity responsible for the study: Outcome Sciences LLC (an IQVIA company). Funding: Bristol-Myers Squibb Pharmaceuticals LTD. Disclosure: M. Wang: Employee of Bristol-Myers Squibb Pharmaceuticals Ltd. S. Menon, B. Martindale: Employee of IQVIA (IQVIA Oncology Dynamics, a syndicated database collecting oncology data).
2-Year Follow-up and High-Risk Subset Analysis of Zuma-1, the Pivotal Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Refractory Large B Cell Lymphoma
Authors: Sattva S. Neelapu, Armin Ghobadi, Caron A. Jacobson, David B. Miklos, Lazaros J. Lekakis, Olalekan O. Oluwole, Yi Lin, Ira Braunschweig, Brian T. Hill, John M. Timmerman, Abhinav Deol, Patrick M. Reagan, Patrick J. Stiff, Ian W. Flinn, Umar Farooq, Andre Goy, Peter A. McSweeney, Javier Munoz, Tanya Siddiqi, Julio C. Chavez, Alex F. Herrera, Allen Xue, Yizhou Jiang, Adrian Bot, John M. Rossi, Jenny J. Kim, William Y. Go, Frederick L. Locke
Journal: Blood (2018)
Tumor Microenvironment Remodeling by Intratumoral Oncolytic Vaccinia Virus Enhances the Efficacy of Immune-Checkpoint Blockade
Authors: Hong Jae Chon, Won Suk Lee, Hannah Yang, So Jung Kong, Na Keum Lee, Eun Sang Moon, Jiwon Choi, Eun Chun Han, Joo Hoon Kim, Joong Bae Ahn, Joo Hang Kim, Chan Kim
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Cancer immunotherapy is a potent treatment modality, but its clinical benefit depends on the tumor's immune profile. Here, we used mJX-594 (JX), a targeted and GM-CSF–armed oncolytic vaccinia virus, as a strategy to remodel the tumor microenvironment (TME) and subsequently increase sensitivity to αPD-1 and/or αCTLA-4 immunotherapy. Experimental Design: The remodeling of the TME was determined using histologic, flow-cytometric, and NanoString immune profiling analyses. JX was intratumorally injected into implanted Renca kidney tumors or MMTV-PyMT transgenic mouse breast cancers with or without αPD-1 and/or αCTLA-4. Various combination regimens were used to evaluate immunotherapeutic anticancer responses. Results: Intratumoral injection of JX remodeled the TME through dynamic changes in the immune system, as shown by increased tumor-infiltrating T cells and upregulation of immune-related gene signatures. This remodeling induced conversion of a noninflamed tumor into an inflamed tumor. JX virotherapy led to enhanced abscopal effects in distant tumors, with increased intratumoral infiltration of CD8+ T cells. A depletion study revealed that GM-CSF is an indispensable regulator of anticancer efficacy of JX. Dual-combination therapy with intratumoral JX and systemic αPD-1 or αCTLA-4 further enhanced the anticancer immune response, regardless of various treatment schedules. Of note, triple combination immunotherapy with JX, αPD-1, and αCTLA-4 elicited the most potent anticancer immunity and induced complete tumor regression and long-term overall survival. Conclusions: Our results show that intratumoral JX treatment induces dramatic remodeling of the TME and more potently suppresses cancer progression with immune-checkpoint blockades by overcoming resistance to immunotherapy.
Variation in Integrated Head and Neck Cancer Care: Impact of Patient and Hospital Characteristics
Authors: Lydia F.J. van Overveld, Robert P. Takes, Jozé C.C. Braspenning, Robert J. Baatenburg de Jong, Jan P. de Boer, John J.A. Brouns, Rolf J. Bun, Eric A. Dik, Boukje A.C. van Dijk, Robert J.J. van Es, Frank J.P. Hoebers, Barry Kolenaar, Arvid Kropveld, Ton P.M. Langeveld, Hendrik P. Verschuur, Jan G.A.M. de Visscher, Stijn van Weert, Max J.H. Witjes, Ludi E. Smeele, Matthias A.W. Merkx, Rosella P.M.G. Hermens
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: Monitoring and effectively improving oncologic integrated care requires dashboard information based on quality registrations. The dashboard includes evidence-based quality indicators (QIs) that measure quality of care. This study aimed to assess the quality of current integrated head and neck cancer care with QIs, the variation between Dutch hospitals, and the influence of patient and hospital characteristics. Methods: Previously, 39 QIs were developed with input from medical specialists, allied health professionals, and patients' perspectives. QI scores were calculated with data from 1,667 curatively treated patients in 8 hospitals. QIs with a sample size of >400 patients were included to calculate reliable QI scores. We used multilevel analysis to explain the variation. Results: Current care varied from 29% for the QI about a case manager being present to discuss the treatment plan to 100% for the QI about the availability of a treatment plan. Variation between hospitals was small for the QI about patients discussed in multidisciplinary team meetings (adherence: 95%, range 88%–98%), but large for the QI about malnutrition screening (adherence: 50%, range 2%–100%). Higher QI scores were associated with lower performance status, advanced tumor stage, and tumor in the oral cavity or oropharynx at the patient level, and with more curatively treated patients (volume) at hospital level. Conclusions: Although the quality registration was only recently launched, it already visualizes hospital variation in current care. Four determinants were found to be influential: tumor stage, performance status, tumor site, and volume. More data are needed to assure stable results for use in quality improvement.
The Functional Meaning of B-Profile During Stress Lung Ultrasound
Authors: Maria Chiara Scali, Angela Zagatina, Quirino Ciampi, Lauro Cortigiani, Antonello D'Andrea, Ana Djordjevic-Dikic, Pablo Martin Merlo, Fabio Lattanzi, Iana Simova, Ines Monte, Claudio Dodi, Jaroslaw D. Kasprzak, Maurizio Galderisi, Alla Boshchenko, Fausto Rigo, Albert Varga, Milica Dekleva, Federica Re, José Luis de Castro e Silva Pretto, Nadezhda Zhuravaskaya, Karina Wierzbowska-Drabik, Katia Coviello, Rodolfo Citro, Paolo Colonna, Clara Carpeggiani, Eugenio Picano
Journal: JACC. Cardiovascular imaging (2018)