tbuckley/cabot-search huggingface dataset:
Immunohistochemical staining for programmed cell-death ligand 1 (PD-L1) in malignant thymoma and thymic carcinoma.
Authors: Alexei Shimanovsky, Richard Cartun, Mary Fiel-Gan, Daniza Mandich, Jonathan Earle, Andrew L. Salner, Katrina Collins, Gregory Alan Otterson, Benjamin F. Chu
Journal: Journal of Clinical Oncology (2017)

e20003 Background: Recent development of anti-PD-1/L1 antibodies has demonstrated activity in various neoplasms. Thymic malignancies (TMS) are rare and treatment in advanced disease is limited. To evaluate the potential impact of anti-PD-1/L1 therapy in TMS, we examined the expression of PD-L1 in previously resected thymoma (TM) and thymic carcinoma (TC). Methods: We examined resected specimens from patients at Hartford Hospital with TM and TC between 2000 and 2014. Expression of PD-L1 was evaluated on formalin-fixed paraffin-embedded tissue. Immunohistochemical testing was done using four different clones of PD-L1 antibodies on the Leica Bond Max automated platform. The four clones include: E1L3N (Cell Signaling Technology), 28-8 (Epitomics) and SP142 (Spring Bioscience), and CAL10 (BioCare). PD-L1 expression was evaluated based on the percentage of tumor cells positive and their intensity graded as negative, weak (1+), moderate (2+), and strong (+3). The scoring was performed by three pathologists and was blinded for clinicopathologic data and antibody clones. Results: We evaluated a total of 29 patients, including 26 patients with TM and 3 with TC. Among the 29 available specimens, 12 had completed PD-L1 expression assessment at the time of submission. PD-L1 expression is present in 75-100% of the evaluated patients. All had positive PD-L1 staining by SP142 and CAL10. Three patients showed strong intensity by CAL10, and one by SP142. E1L3N and 28-8 had positive PD-L1 expression in 9 and 8 patients respectively with weak/moderate intensity. SP142 and CLA10 demonstrated the strongest concordance (R2 = 0.91) but there was significant variation between antibodies (R2 = 0.31-0.91). No correlation was detected between tumor grade and PD-L1 expression. There were focal areas that lacked expression in all of the evaluated specimens. Conclusions: There is increased expression of PD-L1 in TMS. The level of PD-L1 expression varies between the four PD-L1 antibodies. Increased PD-L1 expression provides evidence for the use of PD-L1 inhibitors in TMS. The variable staining highlights the heterogeneity of TMS and challenges in developing predictive biomarker in this cancer.
David Oliver: Outpatient clinics are ripe for reform
Authors: David Oliver
Journal: BMJ (2018)

Traditional specialist outpatient clinics, on which we spend around 7% of the NHS budget, with over 60 million attendances a year and great cost in time and travel to patients, are a prime example of an area that has been relatively neglected amid calls from politicians and the media to reform services.

Simon Stevens, chief executive of NHS England, believes that the current NHS outpatient model is “obsolescent.” Speaking at the NHS Confederation conference in June, he said, “Think of it from the patients’ point of view, think of it from the clinical teams’ point of view, discuss what a redesign would look like, and everything else follows from that.”1

I’d say …
Scientific progress is like doing a puzzle, not building a wall
Authors: Alexa M. Tullett, Simine Vazire
Journal: Behavioral and Brain Sciences (2018)

Abstract We contest the “building a wall” analogy of scientific progress. We argue that this analogy unfairly privileges original research (which is perceived as laying bricks and, therefore, constructive) over replication research (which is perceived as testing and removing bricks and, therefore, destructive). We propose an alternative analogy for scientific progress: solving a jigsaw puzzle.
Abstract 17933: Cardioprotection by GLP-1(28-36) is Mediated by ATP-Dependent Activation of Soluble Adenylyl Cyclase in Coronary Vascular Cells
Authors: Muhammad Ahsan Siraj, Dhanwantee Mundil, Talat Afroze, Eric A Shikatani, Gordon Keller, Mansoor Husain
Journal: Circulation (2016)

Introduction: How the incretin glucagon-like peptide-1 (GLP-1) prevents acute myocardial ischemia-reperfusion injury (IRI) as well as chronic myocardial ischemic injury has not been established. We...
Electrical Connections Between Pulmonary Veins
Authors: AtsushiTakahashi, YoshitoIesaka, YoshihideTakahashi, RyokoTakahashi, KenzaburoKobayashi, KatsumasaTakagi, OsamuKuboyama, TakeoNishimori, HidenobuTakei, HiroshiAmemiya, HideomiFujiwara, MasayasuHiraoka
Journal: Circulation (2002)

Background— Electrical disconnection of the myocardial extensions into arrhythmogenic pulmonary veins (PVs) is recognized as a curative technique for paroxysmal atrial fibrillation (AF). However, the presence of electrical connections between the PVs, which may make achievement of PV disconnection difficult, has not been systematically evaluated. Methods and Results— Forty-nine consecutive patients with drug-resistant AF underwent ostial radiofrequency (RF) catheter ablation of arrhythmogenic PVs with foci triggering AF. Pacing from inside the targeted PV was performed after each RF delivery to identify the left atrial exit site of the residual venoatrial conduction. Successful PV disconnection was defined as achieving elimination of the PV potentials during sinus rhythm or left atrial pacing, and the loss of left atrial conduction during intra-PV pacing. A total of 112 arrhythmogenic PVs were identified. PV disconnection was achieved with 10±6.1 minutes of RF delivery to the ostia of 101 targeted PVs. In...
COPD exacerbations: management and hospital discharge
Authors: A.J. Reis, C. Alves, S. Furtado, J. Ferreira, M. Drummond, C. Robalo-Cordeiro
Journal: Pulmonology (2018)

Chronic Obstructive Pulmonary Disease (COPD) is a serious pulmonary condition. Many patients experience exacerbations and some require Emergency Room visits and hospitalization. In Portugal, hospitalizations due to COPD between 2009 and 2016 decreased by 8%, but they still represented 8049 hospitalized patients in 2016. Appropriate management of COPD exacerbations presents a clinical challenge and, in order to guide therapy, it is important to identify the underlying cause; however, this is not possible in about a third of severe COPD exacerbations. There are several diagnostic tools that can be used to assess an exacerbation and its severity, which will in turn guide treatment, and prognostic scores should be used to predict the risk of future exacerbations. After an exacerbation is appropriately managed, a suitable discharge plan should be prepared. This should generally include reclassification of the patient according to GOLD criteria, optimization of pharmacological therapy, management of comorbidities, patient (or caregiver) education on the correct use of medications, referral to a Pulmonology Outpatient Clinic, if they are not already attending one, and a smoking cessation and respiratory rehabilitation program. In this paper, we will focus on the pharmacological strategies for the management of COPD exacerbations, risk stratification and a hospital discharge plan proposal.
Progress towards universal health coverage in Myanmar: a national and subnational assessment
Authors: Su Myat Han, Md Mizanur Rahman, Md Shafiur Rahman, Khin Thet Swe, Matthew Palmer, Haruka Sakamoto, Shuhei Nomura, Kenji Shibuya
Journal: The Lancet Global Health (2018)

Attainment of universal health coverage is a global health priority. The Myanmar Government has committed to attainment of universal health coverage by 2030, but progress so far has not been assessed. We aimed to estimate national and subnational health service coverage and financial risk protection.We used nationally representative data from the Myanmar Demographic and Health Survey (2016) and the Integrated Household Living Condition Assessment (2010) to examine 26 health service indicators and explored the incidence of catastrophic health payment and impoverishment caused by out-of-pocket payments. We used logistic regression models of inequalities in, and risk factors for, indicators of universal health coverage.Nationally, the coverage of health service indicators ranged from 18·4% (95% CI 14·9-21·9) to 96·2% (95·9-96·5). Coverage of most health services indicators was below the universal health coverage target of 80%. 14·6% (95% CI 13·9-15·3) of households that used health services faced catastrophic health-care payments. 2·0% (95% CI 1·7-2·3) of non-poor households became poor because of out-of-pocket payments for health. Health service coverage and financial risk protection varied substantially by region. Although the richest quintiles had better access to health services than the poorest quintiles, they also had a higher incidence of financial catastrophe as a result of payments for health care. Of the indicators included in the study, coverage of adequate sanitation, no indoor use of solid fuels, at least four antenatal care visits, postnatal care for mothers, skilled birth attendance, and institutional delivery were the most inequitable by wealth quintile.Attainment of universal health coverage in Myanmar in the immediate future will be very challenging as a result of the low health service coverage, high financial risk, and inequalities in access to care. Health service coverage and financial risk protection for vulnerable, disadvantaged populations should be prioritised.Japanese Ministry of Health, Labour and Welfare, Ministry of Education, Culture, Sports, Science and Technology of Japan.
Phosphatidylinositol transfer proteins regulate megakaryocyte TGF-β1 secretion and hematopoiesis in mice
Authors: Maegan Capitano, Liang Zhao, Scott Cooper, Chelsea Thorsheim, Aae Suzuki, Xinxin Huang, Alexander L. Dent, Michael S. Marks, Charles S. Abrams, Hal E. Broxmeyer
Journal: Blood (2018)
Schmorl’s Node
Authors: Manas Kumar Sahoo, Kulbir Ahlawat, Rajiv Yadav, Smeeta Gajendra
Journal: Clinical Nuclear Medicine (2018)

Ga-prostate-specific membrane antigen (PSMA) ligand PET/CT is commonly believed to be prostate specific as the name itself suggests. However, PSMA-expressing nonprostatic cancers as well as benign lesions are continuously being added to the list. We reported PSMA-expressing Schmorl's node in L1 vertebra of a 74-year-old man with prostate cancer. Prostate-specific membrane antigen expression in the vertebral lesion raised a metastatic suspicion. However, on analysis of previous CT scan done 2 years before, the same lesion was observed with no significant interval change, confirming its benign nature. With more use of PSMA ligand PET/CT, more limitations and false positivities will be explored.
Human genome editing is not unethical, says Nuffield Council
Authors: Nigel Hawkes
Journal: BMJ (2018)

There is no moral or ethical objection to making changes to the human genome that would pass down to future generations, as long as certain preconditions are met, the Nuffield Council for Bioethics has concluded.1

Germline engineering, as the technique is sometimes called, was for a long time the red line in biology. Any changes made would become part of the genome of the individual, to be passed on to future generations. The uncertainties and risks were deemed so great that it should never be attempted.

But attitudes have shifted so much that the Nuffield report does not even attempt to restrict the technique to therapeutic uses. It says, rather, that it could be ethically acceptable if it contributes to the welfare of the person born as a consequence and does not increase …
Devalue existing model of general practice and lose its benefits for patients
Authors: Nick Mann
Journal: BMJ (2018)

Pump priming funding enables new models of general practice to exist, not better modelling.1 The pretext for claiming the general practice model is broken is jarringly familiar, joining previous leaders’ similarly specious claims.

The background to this latest clarion call is a GP service that since 2010 has lost more than £3bn (€3.4bn; $4bn) a year in funding and 1500 practices to closures, mergers, and …
Regarding the Congruence Between 2 Circulating Tumor DNA Sequencing Assays—Reply
Authors: Gonzalo Torga, Kenneth J. Pienta
Journal: JAMA Oncology (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 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
Abstract 19944: Targeted Therapy of Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction: Safety and Efficacy in Comparison to IPAH in Compera
Authors: Stephan Rosenkranz, Marius M Hoeper, Doerte Huscher, David Pittrow, Christian F Opitz
Journal: Circulation (2015)

Background: While targeted therapies are available for idiopathic pulmonary arterial hypertension (IPAH), evidence based treatment recommendations for pulmonary hypertension (PH) associated with heart failure and preserved ejection fraction (HFpEF) are lacking. Methods and Results: Out of 5,935 patients in the prospective COMPERA registry, we analyzed patients with “typical” IPAH (n=421, ≤2 of the following risk factors: BMI &gt;30 kg/m2, hypertension, CAD, diabetes and atrial fibrillation at the time of diagnosis), “atypical” IPAH (n=139, &gt;2 risk factors) or PH-HFpEF (n=226) who received targeted PH therapies. Patients with PH-HFpEF, when compared to “typical” and “atypical” IPAH were older (73±8 vs. 62±17 and 71±9 years), had a higher BMI (30 vs. 26 and 32 kg/m2), and more comorbidities (98% vs. 73% and 100%, all p&lt;0.001), respectively. However, mean PAP (46±9 vs. 47±13 and 44±11 mmHg), cardiac index (2.2±0.7 vs. 2,3±0,8 and 2,2±0,8 l/min), and mixed venous oxygen saturation (62±7 vs. 62±10 and 63±9%, all ns) were almost identical. As compared to “typical” and “atypical” IPAH, PH-HFpEF patients had a higher PAWP (20±4 vs. 9±3 and 10±4 mmHg), resulting in a lower calculated PVR (559±270 vs. 861±477 and 784±844 dyn.s.cm-5). Survival at 1, 2 and 3 years post diagnosis was not different between groups. PDE-5 inhibitors were the most common form of initial PH treatment in PH-HFpEF (94%), and combination therapy was less common compared to “typical” or “atypical” IPAH at 1 year (7% vs. 44% and 26%). All 3 groups responded to targeted PH therapies at 12 months, while treatment effects were less pronounced in PH-HFpEF: Compared to baseline, the median increase of the 6MWD at 1 year was 29, 50, and 60 m, respectively. Treatment discontinuations occurred more frequently in patients with PH-HFpEF than in IPAH, either because of side effects or lack of improvement. Conclusions: Despite almost identical alterations of pulmonary artery pressure and cardiac output, patients with PH-HFpEF differed with respect to age, comorbidities and certain hemodynamic features when compared to “typical” or “atypical” IPAH. All groups responded to targeted PH therapy, however tolerability and efficacy of PH drugs were reduced in patients with PH-HFpEF while survival was not different.
Teen Sex, Drug Use Decline
Authors: Bridget M. Kuehn
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 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
Clonal Expansion of Endothelial Cells Contributes to Ischemia-Induced Neovascularization
Authors: Yosif Manavski, Tina Lucas, Simone F. Glaser, Lena Dorsheimer, Stefan Günther, Thomas Braun, Michael A. Rieger, Andreas M. Zeiher, Reinier A. Boon, Stefanie Dimmeler
Journal: Circulation Research (2018)

Rationale: Vascularization is critical to maintain organ function. Although many molecular pathways were shown to control vessel growth, the genuine process of capillary formation under different conditions is unclear. Objective: Here, we elucidated whether clonal expansion contributes to vessel growth by using Confetti mice for genetic tracing of clonally expanding endothelial cells (ECs). Methods and Results: In postnatal retina angiogenesis, we predominantly observed random distribution of fluorescence labeled ECs indicative of random integration or cell mixing. However, in models of pathophysiological angiogenesis (retinopathy of prematurity), as well as ischemia-induced angiogenesis in limbs and hearts, clonally expanded ECs were significantly more abundant (≤69%). Inhibition of VEGFR2 (vascular endothelial growth factor receptor 2) reduced clonal expansion after ischemia. To determine the mechanism underlying clonal expansion in vivo, we assessed gene expression specifically in clonally expanded ECs selected by laser capture microscopy. Clonally expanded ECs showed an enrichment of genes involved in endothelial-to-mesenchymal transition. Moreover, hypoxia-induced clonal expansion and endothelial-to-mesenchymal transition in ECs in vitro suggesting that hypoxia-enhanced endothelial-to-mesenchymal transition might contribute to vessel growth under ischemia. Conclusions: Our data suggest that neovascularization after ischemia is partially mediated by clonal expansion of ECs. Identification of the pathways that control clonal expansion may provide novel tools to augment therapeutic neovascularization or treat pathological angiogenesis.
NHS made “a complete mess” of outsourcing primary care services to Capita, says MP
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

MPs have criticised NHS England for its handling of a contract with the private company Capita to run primary care support services, calling the arrangement short sighted and a shambles.

In a rush to cut the £90m (€101m; $118m) bill for providing these services by a third, NHS bosses failed to consider its impact on the 39 000 GPs, dentists, opticians, and pharmacists affected, says a report from the House of Commons Public Accounts Committee.1

The seven year contract started in August 2015, and problems emerged almost immediately. In May the National Audit Office …
Probiotics to Prevent <i>Clostridium difficile</i> Infection in Patients Receiving Antibiotics
Authors: Joshua Z. Goldenberg, Dominik Mertz, Bradley C. Johnston
Journal: JAMA (2018)

In adults and children prescribed antibiotics, is co-administration of a probiotic associated with a lower risk of symptomatic Clostridium difficile infection without an increase in adverse events?Moderate-quality evidence suggests that probiotics are associated with a lower risk of C difficile infection and very low-quality evidence suggests that probiotics are associated with fewer adverse events vs placebo or no treatment.
HIF inhibition in mRCC: Planned interim analysis of CRLX101 with bevacizumab (bev), a phase 1b/2a.
Authors: Stephen Michael Keefe, Meliessa Hennessey, Janelle Robinson, Kristine Mykulowicz, Orvar Gunnarsson, Ronac Mamtani, David J. Vaughn, Jean H. Hoffman-Censits, Katherine L. Nathanson, Daniel A. Pryma, Scott Eliasof, Edward Graeme Garmey, Roger B. Cohen, Naomi B. Haas
Journal: Journal of Clinical Oncology (2014)

e15611 Background: VHL is inactivated in most clear cell RCC (ccRCC) giving rise to the HIF hypoxia response program and tumor angiogenesis. Antiangiogenic therapies are active in ccRCC, but resistance develops in all patients (pts). Dual inhibition strategies may be needed to overcome resistance. CRLX101 (Cerulean Pharma, Inc., Cambridge, MA, USA), a nano pharmaceutical formulation of camptothecin, has been shown in pre-clinical models to inhibit HIF. We combined CRLX101 with bev in the treatment of pts with refractory mRCC to determine the safety and the recommended phase 2 dose (RP2D) of the combination, and to determine the therapeutic activity of treatment. Methods: Pts with refractory mRCC (all subtypes) were treated every 2 weeks with bev 10 mg/kg and escalating doses of CRLX101 (12 mg/m2, 15 mg/m2) in a standard 3+3 design with an expansion at the RP2D. Pts were treated until progression, death, or prohibitive toxicity. Adverse events were classified using CTCAE v 4.0. Radiographic results were assessed by RECIST v1.1. Results: 12 pts were enrolled on study – 8 clear cell, 2 papillary, 2 chromophobe. Median prior number of therapies was 2. No dose limiting toxicities were observed. CRLX101 at its single-agent RP2D (15 mg/m2) was safely combined with standard bev. 2 episodes of grade 3 non-infectious cystitis and 1 episode of grade 3 hypertension were observed. All other toxicities were grade 1 or 2. The median progression free survival (PFS) was 7.6 months which exceeded our pre-specified threshold and has triggered 2nd stage accrual. 3 of 9 response-evaluable pts (33%) achieved a confirmed partial response (PR) including 1 patient with papillary mRCC; 4 pts (44%) displayed stable disease as their best overall response. Conclusions: Our results demonstrate that CRLX101 can be safely combined with bev in pts with refractory mRCC. The RP2D is 15 mg/m2 q2w of CRLX101 with standard bev. Preliminary outcomes to date suggest that clinical benefit, manifest as prolonged PFS, is conferred to pts with all histologic subtypes of mRCC. Clinical trial information: NCT01625936.
Re: Giorgio Gandaglia, Carlo Andrea Bravi, Paolo Dell’Oglio, et al. The Impact of Implementation of the European Association of Urology Guidelines Panel Recommendations on Reporting and Grading Complications on Perioperative Outcomes after Robot-assisted Radical Prostatectomy. Eur Urol 2018;74:4–7
Authors: Riccardo Bertolo
Journal: European Urology (2018)