tbuckley/cabot-search huggingface dataset:
How primary health care can make universal health coverage a reality, ensure healthy lives, and promote wellbeing for all
Authors: Hans Kluge, Ed Kelley, Shannon Barkley, Pavlos N Theodorakis, Naoko Yamamoto, Alexey Tsoy, Ainur Aiypkhanova, Vidhya Ganesh, David B Hipgrave, Stefan Swartling Peterson, Jose M Valderas, Elias Mossialos
Journal: The Lancet (2018)
PTEN Expression, Not Mutation Status in <i>TSC1, TSC2</i>, or <i>mTOR</i>, Correlates with the Outcome on Everolimus in Patients with Renal Cell Carcinoma Treated on the Randomized RECORD-3 Trial
Authors: Martin H. Voss, David Chen, Albert Reising, Mahtab Marker, Jiayuan Shi, Jianning Xu, Irina Ostrovnaya, Venkatraman E. Seshan, Almedina Redzematovic, Ying-Bei Chen, Parul Patel, Xia Han, James J. Hsieh, A. Ari Hakimi, Robert J. Motzer
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Genomic alterations in key components of PI3K/mTOR pathway have been proposed as candidate predictive markers for rapalog therapy in renal cell carcinoma (RCC). We tested this hypothesis in patients from a randomized phase II trial of everolimus versus sunitinib. Patients and Methods: Archival specimens collected at baseline were analyzed with targeted next-generation sequencing (NGS). Focus of interest were alterations in key PI3K pathway components. PTEN expression was assessed by IHC. Association between molecular findings and treatment outcomes was investigated; same associations were tested for 2 everolimus-treated trial cohorts in gastric and hepatocellular carcinoma (HCC). Results: Among 184 everolimus-treated patients with RCC with NGS data, mutation rates in genes of interest were 6% (TSC1), 4.4% (TSC2), and 8.2% (mTOR); 44% harbored alterations in ≥1 PI3K pathway component. For subjects with presence versus absence of mutations in TSC1, TSC2, or mTOR progression-free survival (PFS) neither differed on univariate analysis (HR, 1.0; P = 0.895) nor on multivariate testing stratified by MSKCC risk group and other established prognostic factors (HR, 1.1; P = 0.806). Everolimus-treated patients with retained (n = 50) versus lost (n = 50) PTEN IHC expression had median PFS of 5.3 months versus 10.5 months (HR, 2.5; P &amp;lt; 0.001). Such differences were not seen with sunitinib (10.9 months vs. 10.3 months; HR, 0.8; P = 0.475). Molecular findings did not correlate with outcomes in gastric and HCC cohorts. Conclusions: Association between mutation status for TSC1/TSC2/mTOR and therapeutic outcome on everolimus was not confirmed. Clinically meaningful differences in PFS were seen based on PTEN expression by IHC, lost in &amp;gt;50% of patients.
GW29-e1810 Cardiac Fibroblast SWELL1 Regulates Post-Myocardial Infarction Ventricular Remodeling and Dysfunction via Caveolin1/STAT3 Signaling.
Authors: Xiyao Chen, Fuyang Zhang, Ling Tao, Xiaoming Wang
Journal: Journal of the American College of Cardiology (2018)
An unusual cause of shortness of breath and palpitations
Authors: G Abraham, M A Ghazanfar, A Bajpai
Journal: BMJ (2018)

A 33 year old woman with recurrent short lived episodes of breathlessness and palpitations for over two years was referred to the cardiology clinic as an outpatient.

She had attended the emergency department several times during the two years of her symptoms, and had undergone various investigations, including two computed tomography pulmonary angiograms for suspected pulmonary embolism (normal both times) and a 24 hour electrocardiogram, which showed sinus rhythm with isolated ventricular ectopics only. She had also experienced one episode of sudden onset slurred speech and right arm weakness which resolved rapidly. Computed tomography imaging of the brain had been normal.

Her symptoms were originally attributed to anxiety and she was prescribed antidepressant medication for anxiety and depression.

In the cardiology clinic, she appeared anxious but otherwise comfortable and well. On examination of the cardiovascular system, heart sounds were normal with no obvious murmur. After review in the cardiology clinic she had an echocardiogram (figs 1, 2).



Fig 1 
Echocardiogram, apical 4 chamber view, of the heart in diastole





Fig 2 
Echocardiogram, apical 4 chamber view, of the heart in systole





### 1. What are the differential diagnoses for intermittent palpitations and paroxysmal dyspnoea in a young woman?

Cardiac causes: primary arrhythmias (eg, supraventricular tachycardia), autonomic dysfunction (eg, postural orthostatic tachycardia syndrome), valvular heart disease, intracardiac masses, cardiomyopathies.

Drug causes : sympathomimetics, excess caffeine, alcohol, salbutamol, cocaine, amphetamines.

Metabolic causes : thyrotoxicosis, …
Evaluation of guideline-endorsed red flags to screen for fracture in patients presenting with low back pain
Authors: Patricia C S Parreira, Christopher G Maher, Adrian C Traeger, Mark J Hancock, Aron Downie, Bart W Koes, Manuela L Ferreira
Journal: British Journal of Sports Medicine (2018)

Objectives (1) Describe the evolution of guideline-endorsed red flags for fracture in patients presenting with low back pain; (2) evaluate agreement between guidelines; and (3) evaluate the extent to which recommendations are accompanied by information on diagnostic accuracy of endorsed red flags. Design Systematic review. Data sources MEDLINE and PubMed, PEDro, CINAHL and EMBASE electronic databases. We also searched in guideline databases, including the National Guideline Clearinghouse and Canadian Medical Association Infobase . Eligibility criteria for selecting studies Evidence-based clinical practice guidelines. Data extraction Two review authors independently extracted the following data: health professional association or society producing guideline, year of publication, the precise wording of endorsed red flag for vertebral fracture, recommendations for diagnostic workup if fracture is suspected, if the guidelines substantiate the recommendation with citation to a primary diagnostic study or diagnostic review, if the guideline provides any diagnostic accuracy data. Results 78 guidelines from 28 countries were included. A total of 12 discrete red flags were reported. The most commonly recommended red flags were older age, use of steroids, trauma and osteoporosis. Regarding the evolution of red flags, older age, trauma and osteoporosis were the first red flags endorsed (in 1994); and previous fracture was the last red flag endorsed (in 2003). Agreement between guidelines in endorsing red flags was only fair; kappa=0.32. Only 9 of the 78 guidelines substantiated their red flag recommendations by research and only nine provided information on diagnostic accuracy. Summary/conclusion The number of red flags endorsed in guidelines to screen for fracture has risen over time; most guidelines do not endorse the same set of red flags and most recommendations are not supported by research or accompanied by diagnostic accuracy data.
Periodontal Disease Was Mildly Associated With an Increased Mortality in 88,882 Men.
Authors: Francisco Lopez-Jimenez, Howard Sesso, Julie Buring, J Michael Gaziano
Journal: Circulation (2001)

P32 We sought to investigate the association between periodontal disease (PD) and total and cardiovascular (CV) mortality in a large cohort of men. Methods: Of 104,388 men in the Physician s Health Study enrollment cohort, 88,882 who had no history of cancer, myocardial infarction, stroke or liver disease and provided information on PD were included in this analysis. A total of 10,264 patients reported history of PD. Results: During a mean follow-up of 5 years, 2,921 patients died, from which 1,461 had a CV death. The crude, age adjusted RR, showed an association between PD and total mortality (RR=1.31, C.I. 1.2-1.4, p&lt;0.0001). Men with PD were more likely to have history of diabetes, hypertension, stable angina, diabetes, and past or current smoking, all with p&lt;0.001. The association between PD and total mortality was substantially attenuated after adjustment for potential confounders (RR=1.14, C.I. 1.02-1.26, p=0.02). Smoking appeared to be an effect modifier because the crude RR between PD and mortality in current or past smokers (RR=1.33, C.I. 1.2-1.5, p&lt;0.0001) was not significantly attenuated after adjustment for potential confounders (RR=1.25, C.I. 1.1-1.4, p&lt;0.0005). A similar association was found with CV mortality, see table. Conclusion: This prospective cohort study suggests that PD is associated with increased mortality, particularly among smokers. However, whether this mild association is real or only due to residual confounding remains to be clarified. Table 1.
Copanlisib monotherapy activity in relapsed or refractory indolent B-cell lymphoma: Combined analysis from phase I and II studies
Authors: P.L. Zinzani, A. Santoro, L. Mollica, G.A. Follows, K. Bouabdallah, F. Morschhauser, A. Patnaik, L. Huang, F. Hiemeyer, A. Benson, I. Genvresse, J.E. Garcia-Vargas, B.H. Childs, M.H. Dreyling
Journal: Annals of Oncology (2018)
Abstract 16821: Key Findings From the AHA Cholesterol Summit
Authors: Comilla Sasson, Mary A Bauman, Vera Bittner, Stephen Daniels, Martha Daviglus, Robert Eckel, Ann M Navar
Journal: Circulation (2017)

Background: High serum cholesterol is a major risk factor for coronary heart disease (CHD). The Check. Change. Control. Cholesterol™ initiative was launched in September 2016 to improve awareness, ...
Abstract PR12: Hedgehog pathway drives fusion-negative rhabdomyosarcoma initiated from nonmyogenic endothelial progenitors
Authors: Catherine J. Drummond, Jason A. Hanna, Matthew R. Garcia, Daniel J. Devine, Alana J. Heyrana, David Finkelstein, Jerold E. Rehg, Mark E. Hatley
Journal: Cancer Research (2018)

Abstract Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Despite aggressive chemotherapy, radiotherapy, and surgery, clinical outcomes for RMS have not improved for three decades, emphasizing the need to uncover the molecular underpinnings of the disease. RMS has been presumed to originate from derailed muscle progenitors based on the histologic appearance and gene expression pattern of the tumors. However, an origin restricted to skeletal muscle does not explain RMS occurring in tissues devoid of skeletal muscle, such as the prostate, bladder, salivary gland, biliary tree, and the omentum. Previously, we described that activation of Sonic Hedgehog signaling through expression of a conditional, constitutively active Smoothened allele, SmoM2, under control of an adipocyte-restricted adipose protein 2 (aP2)-Cre recombinase transgene in mice gives rise to aggressive skeletal muscle tumors that display the histologic and molecular characteristics of human embryonal RMS (ERMS). With the short latency and anatomic restricted tumor location in the neck, we sought to leverage this model to explore the cell of origin of ERMS. Lineage tracing experiments identified aP2-Cre labeled cells are distinctly nonmyogenic and were identified as endothelial cells found in the interstitium between muscle fibers. We illustrate that aP2-Cre is not expressed in the quiescent or activated muscle stem cells or satellite cells. Expression of oncogenic SmoM2 with aP2-Cre results in proliferation and expansion of the aP2-Cre labeled muscle interstitial cells and myogenic transdifferentiation resulting in ERMS. Activation of the Hedgehog pathway in aP2-Cre labeled endothelial progenitors results in Tbx1 expression, which is a skeletal muscle specification factor in the head and neck. We illustrate that endothelium and skeletal muscle within the head and neck arise from Kdr (Vegfr2) expressing progenitors. Hedgehog pathway activation in committed KDR+ endothelial progenitors results in Tbx1 expression and subsequent Myod1 expression driving a partially myogenic program characteristic of ERMS. Our work identifies reprogramming cell fate as a mechanism of transformation in pediatric sarcoma. Citation Format: Catherine J. Drummond, Jason A. Hanna, Matthew R. Garcia, Daniel J. Devine, Alana J. Heyrana, David Finkelstein, Jerold E. Rehg, Mark E. Hatley. Hedgehog pathway drives fusion-negative rhabdomyosarcoma initiated from nonmyogenic endothelial progenitors [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr PR12.
Multiple Lung Masses in a Young Woman
Authors: Boris I. Medarov, Malik M. H. S. Khan, Aakash Modi
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
STAT3 Inhibition Combined with CpG Immunostimulation Activates Antitumor Immunity to Eradicate Genetically Distinct Castration-Resistant Prostate Cancers
Authors: Dayson Moreira, Tomasz Adamus, Xingli Zhao, Yu-Lin Su, Zhuoran Zhang, Seok Voon White, Piotr Swiderski, Xin Lu, Ronald A. DePinho, Sumanta K. Pal, Marcin Kortylewski
Journal: Clinical Cancer Research (2018)

Prostate cancers show remarkable resistance to emerging immunotherapies, partly due to tolerogenic STAT3 signaling in tumor-associated myeloid cells. Here, we describe a novel strategy combining STAT3 inhibition with Toll-like Receptor 9 (TLR9) stimulation to unleash immune response against prostate cancers regardless of the genetic background.We developed and validated a conjugate of the STAT3 antisense oligonucleotide (ASO) tethered to immunostimulatory TLR9 agonist (CpG oligonucleotide) to improve targeting of human and mouse prostate cancer and myeloid immune cells, such as myeloid-derived suppressor cells (MDSC).CpG-STAT3ASO conjugates showed improved biodistribution and potency of STAT3 knockdown in target cells in vitro and in vivo. Systemic administration of CpG-STAT3ASO (5 mg/kg) eradicated bone-localized, Ras/Myc-driven, and Ptenpc-/-Smad4pc-/-Trp53c-/- prostate tumors in the majority of treated mice. These antitumor effects were primarily immune-mediated and correlated with an increased ratio of CD8+ to regulatory T cells and reduced pSTAT3+/PD-L1+ MDSCs. Both innate and adaptive immunity contributed to systemic antitumor responses as verified by the depletion of Gr1+ myeloid cells and CD8+ and CD4+ T cells, respectively. Importantly, only the bifunctional CpG-STAT3ASO, but not control CpG oligonucleotides, STAT3ASO alone, or the coinjection of both oligonucleotides, succeeded in recruiting neutrophils and CD8+ T cells into tumors. Thus, the concurrence of TLR9 activation with STAT3 inhibition in the same cellular compartment is indispensable for overcoming tumor immune tolerance and effective antitumor immunity against prostate cancer.The bifunctional, immunostimulatory, and tolerance-breaking design of CpG-STAT3ASO offers a blueprint for the development of effective and safer oligonucleotide strategies for treatment of immunologically "cold" human cancers.
FDG PET/CT in a Case of Dural Amyloidoma
Authors: Pengcheng Ran, Yupin Liu, Xiang Liang, Yu Zhang, Aisheng Dong
Journal: Clinical Nuclear Medicine (2018)

Dural amyloidoma is an unusual presentation of central nervous system amyloidosis. A 49-year-old woman presented with 1-month history of repeated episodes of vertigo. Precontrast MRI showed dural thickening over right frontal convexity with signal intensity similar to white matter. Postcontrast T1-weighted images showed remarkable enhancement of the lesion. Dural amyloidoma was confirmed by partial resection of the lesion. The patient underwent no further treatment. A follow-up FDG PET/CT showed increased FDG uptake of the residual dural amyloidoma. This case indicates dural amyloidoma should be included in the differential diagnosis of abnormal FDG uptake in dural lesions.
High levels of circulating GM-CSF+CD4+ T cells are predictive of poor outcomes in sepsis patients: a prospective cohort study
Authors: Huihuang Huang, Siyu Wang, Tianjun Jiang, Rong Fan, Zheng Zhang, Jinsong Mu, Ke Li, Yonggang Wang, Lei Jin, Fang Lin, Jie Xia, Lijian Sun, Biao Xu, Chengcheng Ji, Jing Chen, Juan Chang, Bo Tu, Bing Song, Chao Zhang, Fu-Sheng Wang, Ruonan Xu
Journal: Cellular and Molecular Immunology (2018)
Patterns, predictors and subsequent outcomes of disease progression in metastatic renal cell carcinoma patients treated with nivolumab
Authors: Haris Zahoor, Pedro C. Barata, Xuefei Jia, Allison Martin, Kimberly D. Allman, Laura S. Wood, Timothy D. Gilligan, Petros Grivas, Moshe C. Ornstein, Jorge A. Garcia, Brian I. Rini
Journal: Journal for ImmunoTherapy of Cancer (2018)

Nivolumab is approved for the treatment of refractory metastatic renal cell carcinoma. Patterns and predictors of progressive disease (PD) on nivolumab, and outcomes in such patients are lacking.A retrospective analysis of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC) who received nivolumab at Cleveland Clinic (2015-2017) was performed. PD was defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or clinical progression as per treating physician. Univariate analyses (UVA) and multivariate analyses (MVA) were used to identify clinical and laboratory markers as potential predictors of progression-free survival (PFS).Ninety patients with mean age of 65, 74% men, and 83% good or intermediate International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group were included. Median number of prior systemic treatments was 2 (range, 1-6). Median overall survival (OS) and PFS were 15.8 and 4.4 months, respectively. Fifty-seven patients (63%) had PD and 44% of patients with radiographic PD had new organ sites of metastases with brain (8/23, 35%) being the most common. Twelve patients received treatment beyond progression (TBP), and among 6 patients with available data, 3 (50%) had any tumor shrinkage (2 pts. with 17% shrinkage, one pt. with 29% shrinkage). Of 57 patients with PD, 28 patients (49%) were able to initiate subsequent treatment, mainly with axitinib and cabozantinib, while 40% of patients were transitioned to hospice after PD. In MVA, a higher baseline Neutrophil-to-Lymphocyte ratio (NLR) (HR, 1.86; 95% CI, 1.05-3.29; p = 0.033) was associated with an increased risk of progression, whereas higher (> 0.1 k/uL) baseline eosinophil count was associated with a lower risk of progression (HR, 0.54; 95% CI, 0.30-0.98; p = 0.042).Brain was the most common site of PD in patients treated with nivolumab, and only half of patients progressing on nivolumab were able to initiate subsequent treatment. The risk of PD increased with a higher baseline NLR and reduced with a higher baseline eosinophil count.
Head and neck (HN) primary sarcomatoid carcinoma (PSC) profile by high-throughput somatic mutation profiling
Authors: V. Fallet, R. Taouachi, R. Saffroy, A. Ben Lakhdar, N. Rabbe, F. André, S. Temam, A. Lemoine, M. Wislez
Journal: Annals of Oncology (2018)
Pleiotropic effects of metformin: Shaping the microbiome to manage type 2 diabetes and postpone ageing
Authors: Francesco Prattichizzo, Angelica Giuliani, Emanuela Mensà, Jacopo Sabbatinelli, Valeria De Nigris, Maria Rita Rippo, Lucia La Sala, Antonio Domenico Procopio, Fabiola Olivieri, Antonio Ceriello
Journal: Ageing Research Reviews (2018)
Preclinical evaluation of a non-depleting, first-in-class humanized IgG4 agonist anti-ICOS antibody
Authors: S. Brett, S. Yadavilli, L. Seestaller-Wehr, S. Bhattacharya, H. Jackson, M. Bi, J. Willoughby, T. Zhang, Y.-B. Liu, Y.K. Katlinskaya, H. Shi, J. Jing, A. Hahn, S. Speller, D. David Figueroa, J. Yu, D. Olive, M. Cragg, P. Mayes, A. Hoos
Journal: Annals of Oncology (2018)
BRAVERY study: A multicenter phase II study of eribulin in patients with BRAF V600E mutant metastatic colorectal cancer (EPOC1701)
Authors: T. Masuishi, H. Taniguchi, D. Kotani, H. Bando, Y. Komatsu, K. Yamaguchi, T.E. Nakajima, T. Satoh, T. Nishina, T. Esaki, M. Wakabayashi, S. Nomura, S. Sakamoto, H. Ono, N. Hirano, N. Fujishiro, N. Fuse, A. Sato, A. Ohtsu, T. Yoshino
Journal: Annals of Oncology (2018)
Functional inhibition of TGF-β in colorectal cancer cells and its interaction with AXL receptor
Authors: D. Ciardiello, G. Martini, N. Matrone, V. Belli, P.P. Vitiello, C. Cardone, V. Ciaramella, G. Barra, L. Poliero, C. Borrelli, T. Troiani, D. Melisi, F. Morgillo, E.F. Giunta, V. De Falco, F. Ciardiello, E. Martinelli
Journal: Annals of Oncology (2018)
Improving value for cancer patients: A European study of outcomes in practice
Authors: R. Hazarika, T. Albreht, B. Berger, D. Duplay, L. Makaroff, Z. Maravic, R. Mortuza, V. Muthu, K. Oliver, R. Price, M.V.M. van Meerveld, K. Steinmann, A. Krukowsk, R. Catena, S. Wait, V. Zilli
Journal: Annals of Oncology (2018)
Efficacy and safety of brodalumab in patients with psoriasis who had inadequate responses to ustekinumab: subgroup analysis of two randomized phase <scp>III</scp> trials
Authors: R.G. Langley, A.W. Armstrong, M.G. Lebwohl, A. Blauvelt, S. Hsu, S. Tyring, S. Rastogi, R. Pillai, R. Israel
Journal: British Journal of Dermatology (2018)

Background Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, has demonstrated superior efficacy and safety over ustekinumab as induction therapy for moderate-to-severe psoriasis. Objectives To evaluate the efficacy and safety of brodalumab through week 52 in patients who had inadequate responses to ustekinumab. Methods A subgroup analysis of the phase III AMAGINE-2/-3 double-blind randomized controlled trials was performed. Participants were aged 18–75 years and had a Psoriasis Area and Severity Index (PASI) ≥ 12, static Physician's Global Assessment score ≥ 3 and involvement of ≥ 10% body surface area. The studies were registered at ClinicalTrials.gov: AMAGINE-2, NCT01708603; AMAGINE-3, NCT01708629. Results At baseline, patients with or without prior biologic experience who had an adequate response at week 16 on ustekinumab or brodalumab had lower rates of involved body surface area, PASI, prior biologic use, psoriatic arthritis and body mass index than patients who experienced inadequate response at or after week 16. Among patients who experienced inadequate response to ustekinumab, those rescued with brodalumab had PASI ≥ 75%, ≥ 90% and 100% improvement response rates of 72·6%, 58·1% and 36·3%, respectively, at week 52 compared with 61·7%, 25·5% and 5·4%, respectively, in patients who continued ustekinumab. Exposure-adjusted rates of treatment-emergent adverse events were similar among patients rescued with brodalumab (377·3 adverse events per 100 patient-years) and those who remained on ustekinumab (389·9 adverse events per 100 patient-years). Conclusions Among patients who experienced inadequate responses to ustekinumab, rescue with brodalumab improved skin clearance outcomes compared with continuing ustekinumab.
P3.11-11 Improving Timeliness of Lung Cancer Diagnostic Services with the Implementation of Coordinated Care via a “Navigation Day”
Authors: M. Gulak, C. Bornais, S. Shin, L. Murphy, J. Smylie, J. Pantarotto, M. Fung-Kee-Fung, D. Maziak
Journal: Journal of Thoracic Oncology (2018)