tbuckley/cabot-search huggingface dataset:
Effect of omeprazole and AlOH/MgOH on riociguat absorption
Authors: Corina Becker, Reiner Frey, Sigrun Unger, Ulrike Artmeier-Brandt, Gerrit Weimann, Wolfgang Mueck
Journal: European Respiratory Journal (2013)

Introduction 

Riociguat, an oral soluble guanylate cyclase stimulator, is under investigation for pulmonary hypertension treatment.

Aims 

Pharmacokinetic (PK) studies investigated the influence of omeprazole and AlOH/MgOH on riociguat absorption and bioavailability.

Methods 

Oral, single-dose, immediate-release riociguat 2.5 mg was characterized in 2 open-label, randomized, crossover studies in healthy males: 1) 4–day omeprazole 40 mg od pre-treatment followed by co-treatment with omeprazole + riociguat vs riociguat alone on Day 5 (n=12); 2) co-treatment with 10 mL AlOH/MgOH + riociguat vs riociguat alone (n=12).

Results 

Riociguat bioavailability was decreased slightly by pre- and co-treatment with omeprazole and co-treatment with 10 mL AlOH/MgOH (Table 1). This is considered of minor clinical relevance.

View this table:

Table 1. Point estimates (LS means) and 90% CIs for ratios of AUC and Cmax (ANOVA).





The most common AEs in subjects treated with riociguat +/- omeprazole and AlOH/MgOH across the 2 studies were headache (44%) and abdominal pain upper (8%). No serious AEs were reported.

Conclusions 

The results confirm the slightly reduced absorption of riociguat in neutral vs acidic medium. This is considered of minor clinical relevance. Riociguat +/- omeprazole or AlOH/MgOH was well tolerated with a good safety profile. Antacids should be taken at least 1 h after riociguat administration.
Abstract 273: Noninvasive Mitochondrial Modulation: Neuroprotection in a Translational Model of Cardiac Arrest and Resuscitation
Authors: Joseph M Wider, Erin Gruley, Jennifer Mathieu, Emma Murphy, Rachel Mount, Brian J Oneil, Karin Przyklenk, Robert W Neumar, Maik Huttemann, Thomas H Sanderson
Journal: Circulation (2019)

Background: Mitochondrial dysfunction contributes to cardiac arrest induced brain injury and has been a target for neuroprotective therapies. An emerging concept suggests that hyperactivation of neuronal mitochondria following resuscitation results in hyperpolarization of the mitochondrial membrane during reperfusion, which drives generation of excess reactive oxygen species. Previous studies from our group demonstrated that limiting mitochondrial hyperactivity by non-invasively modulating mitochondrial function with specific near infrared light (NIR) wavelengths can reduce brain injury in small animal models of global and focal ischemia. Hypothesis: Inhibitory wavelengths of NIR will reduce neuronal injury and improve neurocognitive outcome in a clinically relevant swine model of cardiac arrest. Methods: Twenty-eight male and female adult swine were enrolled (3 groups: Sham, CA/CPR, and CA/CPR + NIR). Cardiac arrest (8 minutes) was induced with a ventricular pacing wire and followed by manual CPR with defibrillation and epinephrine every 30 seconds until return of spontaneous circulation (ROSC), 2 of the 20 swine that underwent CA did not achieve ROSC and were not enrolled. Treatment groups were randomized prior to arrest and blinded to the CPR team. Treatment was applied at onset of ROSC by irradiating the scalp with 750 nm and 950 nm LEDs (5W) for 2 hours. Results: Sham-operated animals all survived (8/8), whereas 22% of untreated animals subjected to cardiac arrest died within 45 min of ROSC (CA/CPR, n= 7/9). All swine treated with NIR survived the duration of the study (CA/CPR + NIR, n=9/9). Four days following cardiac arrest, neurological deficit score was improved in the NIR treatment group (50 ± 21 CA/CPR vs. 0.8 ± 0.8 CA/CPR + NIR, p &lt; 0.05). Additionally, neuronal death in the CA1/CA3 regions of the hippocampus, assessed by counting surviving neurons with stereology, was attenuated by treatment with NIR (17917 ± 5534 neurons/mm 3 CA/CPR vs. 44655 ± 5637 neurons/mm 3 CA/CPR + NIR, p &lt; 0.05). All data is reported as mean ± SEM. Conclusions: These data provide evidence that noninvasive modulation of mitochondria, achieved by transcranial irradiation of the brain with NIR, mitigates post-cardiac arrest brain injury.
Wolff-Parkinson-White Syndrome
Authors: S. RAMACHANDRAN
Journal: Circulation (1972)

This paper reports a patient with Wolff-Parkinson-White syndrome who presented with a tachycardia showing an unusual QRS morphology closely resembling that of a ventricular tachycardia. On reversal to a normal rhythm the electrocardiogram showed changes of a type A preexcitation, with subsequent conversion to a type B pattern. This phenomenon was observed on two separate occasions. Such conversion would suggest the presence of two distinct sites for bypass location resulting in preexcitation, thus lending support to the theory of aberrant atrioventricular conduction via a bundle of Kent or neuromuscular tissue connecting atrium to ventricle. The configuration of the QRS complexes during the tachycardia would appear to be due to a circus movement with antegrade anomalous atrioventricular conduction and retrograde atrial stimulation via the bundle of His, although in this case, due to the presence of two distinct anomalous atrioventricular conduction pathways, both antegrade and retrograde conduction via these two pathways alone cannot be excluded.
Immunotherapy With Programmed Cell Death 1 vs Programmed Cell Death Ligand 1 Inhibitors in Patients With Cancer
Authors: Serban Ghiorghiu, Pralay Mukhopadhyay, Cristian Massacesi
Journal: JAMA Oncology (2020)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
A prospective randomized controlled trial of hydrating nail solution for prevention or treatment of onycholysis in breast cancer patients who received neoadjuvant/adjuvant docetaxel chemotherapy.
Authors: Ji-Yeon Kim, Oh-Nam Ok, Jeong Ju Seo, Soo-Hyeon Lee, Jin Seok Ahn, Yeon Hee Park
Journal: Journal of Clinical Oncology (2017)

10108 Background: Onycholysis and other nail toxicities occur in approximately 20-30% of breast cancer(BC) patients receiving docetaxel(D) chemotherapy. Onycholysis, the separation of the nail plate from nail bed, is also often associated with painful paronychia decreasing patients’ the efficacy of a hydrating nail solution (EVONAIL solution, Evaux Laboratories, France) for the prevention and treatment of D-induced onycholysis and nail toxicities. Methods: This study is a prospective randomized controlled study of hydrating nail solution for prevention or treatment of onycholysis in patients with BC receiving neo/adjuvant 3-weekly D after doxorubicin plus cyclophosphamide. In experimental arm, each patient painted hydrating nail solution on nails and periungual areas once a day till developing onycholysis grade 2 or more. After Gr 2 onycholysis development, patients painted EVONAIL twice a day regardless of treatment arms. The primary endpoint is the incidence of onycholysis Gr 2 or more and recovery rate from Gr2 onycholysis. The secondary endpoints include: the incidence of all grade onycholysis; duration from first docetaxel treatment until onycholysis symptom appearance; degree of pain from nail toxicities; the incidence of other nail toxicities. Results: Since Aug 2015 to May 2016, 103 patients were enrolled and completed this study (Experimental arm(E) : 51, control arm(C): 52). Of 103 patients, 25 cases of Gr1 and 22 of Gr2 onycholysis were observed (Gr1 and 2(n,(%)) : 8(15.7%) and 7(13.7%) in E, 17(32.7%) and 15(21.4%)in C, respectively). Hydrating nail solution resulted in statistically significant reduction of Gr2 onycholysis compared to C (HR = 0.39, 95% CI 0.16, 0.96; P = 0.041) and all grade onycholysis decreased in experimental arm with statistical significance (HR = 0.37, 95% CI 0.20-0.69, P = 0.002). However, the effect of onycholysis treatment was not observed. Conclusions: Hydrating nail solution significantly reduced the incidence of D induced onycholysis in BC patients (NCT02670603). Clinical trial information: NCT02670603.
Comparable Cancer-Specific Mortality of Patients With Early Gastric Cancer Treated With Endoscopic Therapy vs Surgical Resection
Authors: MirMilad Khoshknab Pourmousavi, Rui Wang, Tossapol Kerdsirichairat, Ayesha Kamal, Venkata S. Akshintala, Gulara Hajiyeva, Chawin Lopimpisuth, Yuri Hanada, Vivek Kumbhari, Vikesh K. Singh, Mouen A. Khashab, Olaya Gutierrez Brewer, Eun Ji Shin, Marcia I. Canto, Anne Marie Lennon, Saowanee Ngamruengphong
Journal: Clinical Gastroenterology and Hepatology (2020)
CD11b Regulates Fungal Outgrowth but Not Neutrophil Recruitment in a Mouse Model of Invasive Pulmonary Aspergillosis
Authors: Daniel Teschner, Anna Cholaszczyńska, Frederic Ries, Hendrik Beckert, Matthias Theobald, Stephan Grabbe, Markus P. Radsak, Matthias Bros
Journal: Blood (2018)
Cost effectiveness of lowering cholesterol
Authors: J Shepherd
Journal: BMJ (1996)

Cost effectiveness of lowering cholesterolCost consequence analysis may be more useful to decision makers EDrroR,-If economic analyses are to provide guidance on population health strategies they should consider all relevant costs and consequences associated with medical interventions.We have identified five methodological deficien- cies in the economic analysis of P D P Pharoah and W Hollingworth.'
A critical appraisal of the quality of glioma imaging guidelines using the AGREE II tool: A EuroAIM initiative.
Authors: Sotirios Bisdas, Valeria Romeo, Arnaldo Stanzione, Lorenzo Ugga, Renato Cuocolo, Sirio Cocozza, Arturo Brunetti, Faiq Shaikh, Diana Roettger
Journal: Journal of Clinical Oncology (2019)

e13553 Background: Following the EuroAIM initiative to assess the quality of medical imaging guidelines by using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, we aimed to evaluate the quality of the current imaging guidelines in patients with gliomas. Methods: A literature search was conducted to identify eligible imaging guidelines considered in the management of adult patients with gliomas. The selected guidelines were evaluated using the AGREE II instrument by four independent appraisers. The agreement among the four appraisers was estimated using the intraclass correlation coefficient (ICC) analysis. Results: Seven guidelines were selected for the appraisal. Six out of the seven guidelines showed an average level of quality with only one showing a low quality. The highest scores were found in Domain 1 “Scope and purpose” (mean score = 81.2%) and Domain 4 “Clarity of presentation” (mean score = 77.6%). The remaining domains showed a low level of quality and, in particular, Domain 5 “Applicability” was the most critical with a mean score of 41.7%. The ICC analysis showed a very good agreement among the four appraisers with ICC values ranging from 0.907 to 0.993. Conclusions: The available guidelines on glioma imaging emerged as of average quality according to the AGREE II tool analysis. Based on these results, further efforts should be made in order to involve different professional bodies and stakeholders and increase patient and public involvement in any future guideline drafting as well as to improve the applicability of these guidelines into the clinical practice.
Telomere Time—Why We Should Treat Biological Age Cautiously
Authors: Daniel A. Notterman, Lisa Schneper
Journal: JAMA Network Open (2020)

Dries S. Martens, PhD; Bram G. Janssen, PhD; Esmée M. Bijnens, PhD; Diana B. P. Clemente, PhD; Paolo Vineis, PhD; Michelle Plusquin, PhD; Tim S. Nawrot, PhD
HACE1 Prevents Lung Carcinogenesis via Inhibition of RAC-Family GTPases
Authors: Melanie Kogler, Luigi Tortola, Gian Luca Negri, Alexandra Leopoldi, Amal M. El-Naggar, Stefan Mereiter, Carlos Gomez-Diaz, Roberto Nitsch, Davide Tortora, Anoop M. Kavirayani, Bianca V. Gapp, Shuan Rao, Iris Uribesalgo, David Hoffmann, Domagoj Cikes, Maria Novatchkova, David A. Williams, Jeffrey M. Trent, Fumiyo Ikeda, Mads Daugaard, Astrid Hagelkruys, Poul H. Sorensen, Josef M. Penninger
Journal: Cancer Research (2020)

HACE1 is an E3 ubiquitin ligase with important roles in tumor biology and tissue homeostasis. Loss or mutation of
BODY COMPOSITION AND SURVIVAL IN STABLE CORONARY HEART DISEASE: IMPACT OF LEAN MASS INDEX AND BODY FAT IN THE “OBESITY PARADOX”
Authors: Alban DeSchutter, Carl J. Lavie, Richard V. Milani, Surya M. Artham, Dharmendrakumar A. Patel
Journal: Journal of the American College of Cardiology (2011)
Acute Cor Pulmonale in Critically Ill Patients with Covid-19
Authors: Christina Creel-Bulos, Maxwell Hockstein, Neha Amin, Samer Melhem, Alexander Truong, Milad Sharifpour
Journal: New England Journal of Medicine (2020)

Acute Cor Pulmonale in Covid-19 Five cases of acute cor pulmonale in patients with Covid-19 are described. Although acute pulmonary thromboembolism was the most likely cause of right ventricular fa...
Small-molecule activating SIRT6 elicits therapeutic effects and synergistically promotes anti-tumor activity of vitamin D<sub>3</sub> in colorectal cancer
Authors: Jialin Shang, Zhehui Zhu, Yingyi Chen, Jinglue Song, Yuji Huang, Kun Song, Jie Zhong, Xinyuan Xu, Jiacheng Wei, Chengxiang Wang, Long Cui, Chen-Ying Liu, Jian Zhang
Journal: Theranostics (2020)

Colorectal cancer (CRC) is the leading cause of cancer death; however, targets with broad anti-CRC effects are limited.Sirtuin6 (SIRT6) is a conserved nicotinamide adenine dinucleotide (NAD + )-dependent deacetylase that is widely pathologically downregulated in CRC, but its pharmacological effect in CRC remains undefined due to the lack of small-molecule SIRT6 activators.We searched for a compound activating SIRT6 and investigated its anti-CRC effect in various models.Methods: We identified an allosteric SIRT6 activator, MDL-811.Its ability to enhance SIRT6 deacetylation at protein and cellular levels was evaluated by Fluor de Lys (FDL) and western blots.We assessed the proliferation of 26 CRC cell lines and patient-derived organoids (PDOs) treated with MDL-811.In vivo efficacy of MDL-811 was evaluated in HCT116 cell line-and patient-derived xenografts as well as a spontaneous CRC model.RNA sequencing and real-time quantitative PCR assays were performed to analyze gene expression changes in MDL-811-treated HCT116 cells.Along with controls in SIRT6-overexpressing HCT116 cells, the SIRT6-mediated histone H3 deacetylation at the Cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene locus was assessed by chromatin immunoprecipitation (ChIP) in MDL-811-treated HCT116 cells.A combination therapy against CRC based on the downstream gene of SIRT6 activation was evaluated in cells and mouse models.Results: MDL-811 significantly activated SIRT6 histone H3 deacetylation (H3K9Ac, H3K18Ac, and H3K56Ac) in vitro and had broad antiproliferative effects on diverse CRC cell lines and PDOs.More importantly, the in vivo anti-tumor efficacy of MDL-811 was demonstrated across cell line-and patient-derived xenografts and in the APC min/+ spontaneous CRC model.Mechanically, we identified a new downstream target gene of SIRT6 in CRC, CYP24A1.Based on these findings, a combination drug strategy with MDL-811 to synergistically enhance the anti-CRC effect of vitamin D3 was validated in vitro and in vivo.Conclusions: Our data provide proof of concept that targeting SIRT6 using a small-molecule activator is an attractive therapeutic strategy for CRC and that MDL-811 could be a promising lead compound for further preclinical and clinical studies of treatments for CRC.
Medium-throughput Drug Screening of Patient-derived Organoids from Colorectal Peritoneal Metastases to Direct Personalized Therapy
Authors: Vignesh Narasimhan, Josephine A. Wright, Michael Churchill, Tongtong Wang, Rachele Rosati, Tamsin R.M. Lannagan, Laura Vrbanac, Anne B. Richardson, Hiroki Kobayashi, Timothy Price, Gayle X.Y. Tye, Julie Marker, Peter J. Hewett, Michael P. Flood, Shalini Pereira, G. Adam Whitney, Michael Michael, Jeanne Tie, Siddhartha Mukherjee, Carla Grandori, Alexander G. Heriot, Daniel L. Worthley, Robert G. Ramsay, Susan L. Woods
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Patients with colorectal cancer with peritoneal metastases (CRPMs) have limited treatment options and the lowest colorectal cancer survival rates. We aimed to determine whether organoid testing could help guide precision treatment for patients with CRPMs, as the clinical utility of prospective, functional drug screening including nonstandard agents is unknown. Experimental Design: CRPM organoids (peritonoids) isolated from patients underwent parallel next-generation sequencing and medium-throughput drug panel testing ex vivo to identify specific drug sensitivities for each patient. We measured the utility of such a service including: success of peritonoid generation, time to cultivate peritonoids, reproducibility of the medium-throughput drug testing, and documented changes to clinical therapy as a result of the testing. Results: Peritonoids were successfully generated and validated from 68% (19/28) of patients undergoing standard care. Genomic and drug profiling was completed within 8 weeks and a formal report ranking drug sensitivities was provided to the medical oncology team upon failure of standard care treatment. This resulted in a treatment change for two patients, one of whom had a partial response despite previously progressing on multiple rounds of standard care chemotherapy. The barrier to implementing this technology in Australia is the need for drug access and funding for off-label indications. Conclusions: Our approach is feasible, reproducible, and can guide novel therapeutic choices in this poor prognosis cohort, where new treatment options are urgently needed. This platform is relevant to many solid organ malignancies.
Glucose-dependent partitioning of arginine to the urea cycle protects β-cells from inflammation
Authors: Accalia Fu, Juan Carlos Alvarez-Perez, Daina Avizonis, Tatsuya Kin, Scott B. Ficarro, Dong Wook Choi, Esra Karakose, Mehmet G. Badur, Lindsay Evans, Carolina Rosselot, Gaelle Bridon, Gregory H. Bird, Hyuk-Soo Seo, Sirano Dhe-Paganon, Jurre J. Kamphorst, Andrew F. Stewart, A. M. James Shapiro, Jarrod A. Marto, Loren D. Walensky, Russell G. Jones, Adolfo Garcia-Ocana, Nika N. Danial
Journal: Nature Metabolism (2020)
PTH-021 Cancer and adenoma detection rate in 2-week wait colonoscopy and CT colonography- tertiary centre experience
Authors: Sardar Chaudhary, Jay Pancholi, Catalin Ivan, Ratan Verma, Mosheir Elabassy, Richard J Robinson, James A Stephenson
Journal: Endoscopy (2018)

<h3>Introduction</h3> Computed Tomography Colonoscopy (CTC) is increasingly being used as an alternative to optical colonoscopy (OC). The SIGGAR trial and COCOS study have shown CTC to be an accurate and safe alternative to OC for diagnosis of colorectal cancer (CRC) and large polyps. Our aim was to compare various performance indicators between CTC and OC in the lower GI straight to test (STT) 2 week wait (2 WW) pathway. <h3>Methods</h3> The investigation of choice for the lower GI 2 WW STT cohort between Nov 2014 and Oct 2015 was OC with CTC being the first-line test between Jan 2016 and Dec 2016. We retrospectively analysed 12 months' data for both cohorts. Outcomes included completion rate, polyp detection rate (PDR), adenoma detection rate (ADR) and CRC detection rates. <h3>Results</h3> 1135 patients attended for OC versus 1829 for CTC. Significantly more OC were cancelled on the day compared to CTC (6.5% v 2% p=0.0001). OC had a completion rate measured by caecal intubation of 86% versus 100% of CTC (p=0.0001). The diagnostic study rate measured by adequate bowel preparation/faecal tagging and distension was 89.3% at OC (adequate preparation) versus 98.4% for CTC (p=0.0001). CRC detection rate was 4.5% (95% CI 3.43% to 5.95%) in the OC group versus 4.9% (95% CI 3.97% to 5.95%) in the CTC group (p=&gt;0.005). The PDR was significantly higher in the OC group compared to the CTC group (25.1% (95% CI 22.95% to 27.32%) v 13.5% (95% CI 11.95% to 15.11%) p=0.0001). However, 61.7% of the polyps detected at OC were ≤5 mm which are not routinely reported on CTC. PDR for polyps&gt;5 mm at OC was 9.6% (95% CI 7.98% to 11.54%) versus 13.5% at CTC (p=0.0024). The ADR at OC was significantly higher than in the CTC (16.5% (95% CI 14.38% to 18.85%) versus 9.8% (95% CI 8.53% to 11.29%) p=0.0001). The non-CRC detection rate in the CTC group was 4.3%. <h3>Conclusions</h3> CTC and OC have comparable CRC detection rates for patients referred via the 2 WW STT lower GI pathway. However, the PDR and ADR are higher with OC, this data is skewed by the number of diminutive polyps identified at OC that are not routinely reported at CTC. Also, a number of cases with 5–10 mm polyps at CTC did not progress to OC. Long term follow up data is required to compare interval cancer detection rates in these cohorts to assess the impact of not reporting/identifying sub 5 mm polyps. From a service delivery perspective, the on the day cancellation rate, completion rate and diagnostic study rate for CTC were significantly better than OC in the STT patient. An additional benefit of CTC is the diagnosis of non-colonic cancers, the rate of which was comparable to the CRC rate.
Life at the Editorial “COVID Frontline”. The American Thoracic Society Journal Family
Authors: Sanjay H. Chotirmall, Fernando J. Martinez, Paul T. Schumacker, Colin R. Cooke, Nitin Seam, Laurent Brochard, Robert M. Tighe, Bruce D. Levy, Diane Gern, Jadwiga A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

We live in extraordinary times, facing the greatest medical crisis of the last century and potentially of all time.The growing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic affects each of us, our families, and our very way of life.Our core American Thoracic Society (ATS) journal readership, making up a significant number of individuals on the clinical and research frontlines, places us in a privileged position: the "editorial frontline" tasked to provide timely, robust, and scientifically sound information to inform clinical practice and research.With this role comes great responsibility and during a global pandemic requires real-time responses, accelerated peer review processes, and a timely, agile governance cadence.Although this is a challenge, the digital era of publication accelerates information availability at speeds inaccessible in past pandemics. Putting Safety FirstOur priority as editors is first safeguarding patient and physician safety by ensuring the scientific accuracy of submitted work: publishing stringently peer-reviewed data using accurate, responsible, and ethical approaches, while ensuring timely publication to facilitate advancements in knowledge and clinical care.Charged by the ATS with the responsibility of transitioning data into the public domain, our role requires time, focus, and a meticulous approach, in reality, working at the "editorial frontline."During a global pandemic, we face a set of unique issues where publishing data at speed must be balanced against maintaining standards and rigor.Here we provide a view from that frontline for our international readership.