tbuckley/cabot-search huggingface dataset:
Phase 3 Assessment of the Automated Bone Scan Index as a Prognostic Imaging Biomarker of Overall Survival in Men With Metastatic Castration-Resistant Prostate Cancer
Authors: Andrew J. Armstrong, Aseem Anand, Lars Edenbrandt, Eva Bondesson, Anders Bjartell, Anders Widmark, Cora N. Sternberg, Roberto Pili, Helen Tuvesson, Örjan Nordle, Michael A. Carducci, Michael J. Morris
Journal: JAMA Oncology (2018)

Prostate cancer commonly metastasizes to bone, and bone metastases are associated with pathologic fractures, pain, and reduced survival. Bone disease is routinely visualized using the technetium Tc 99m (99mTc) bone scan; however, the standard interpretation of bone scan data relies on subjective manual assessment of counting metastatic lesion numbers. There is an unmet need for an objective and fully quantitative assessment of bone scan data.To clinically assess in a prospectively defined analysis plan of a clinical trial the automated Bone Scan Index (aBSI) as an independent prognostic determinant of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC).This investigation was a prospectively planned analysis of the aBSI in a phase 3 multicenter randomized, double-blind, placebo-controlled clinical trial of tasquinimod (10TASQ10). Men with bone metastatic chemotherapy-naïve CRPC were recruited at 241 sites in 37 countries between March 2011 and August 2015. The statistical analysis plan to clinically evaluate the aBSI was prospectively defined and locked before unmasking of the 10TASQ10 study. The analysis of aBSI was conducted between May 25, 2016, and June 3, 2017.The associations of baseline aBSI with OS, radiographic progression-free survival (rPFS), time to symptomatic progression, and time to opiate use for cancer pain.Of the total 1245 men enrolled, 721 were evaluable for the aBSI. The mean (SD) age (available for 719 men) was 70.6 (8.0) years (age range, 47-90 years). The aBSI population was representative of the total study population based on baseline characteristics. The aBSI (median, 1.07; range, 0-32.60) was significantly associated with OS (hazard ratio [HR], 1.20; 95% CI, 1.14-1.26; P < .001). The median OS by aBSI quartile (lowest to highest) was 34.7, 27.3, 21.7, and 13.3 months, respectively. The discriminative ability of the aBSI (C index, 0.63) in prognosticating OS was significantly higher than that of the manual lesion counting (C index, 0.60) (P = .03). In a multivariable survival model, a higher aBSI remained independently associated with OS (HR, 1.06; 95% CI, 1.01-1.11; P = .03). A higher aBSI was also independently associated with time to symptomatic progression (HR, 1.18; 95% CI, 1.13-1.23; P < .001) and time to opiate use for cancer pain (HR, 1.21; 95% CI, 1.14-1.30; P < .001).To date, this investigation is the largest prospectively analyzed study to validate the aBSI as an independent prognostic imaging biomarker of survival in mCRPC. These data support the prognostic utility of the aBSI as an objective imaging biomarker in the design and eligibility of clinical trials of systemic therapies for patients with mCRPC.ClinicalTrials.gov Identifier: NCT01234311.
Abstract 14884: Morphometric and Hemodynamic Analysis of Human Stenotic Vertebrobasilar System
Authors: Yundi Feng, Yulong Huo
Journal: Circulation (2016)

Introduction: Approximately 80% of strokes can be attributed to the ischemic origin, of which 20~25% are located in posterior circulation. Basilar artery (BA) and vertebral arteries (VA) are two fr...
Phase II Study of Maintenance Pembrolizumab in Patients with Extensive-Stage Small Cell Lung Cancer (SCLC)
Authors: Shirish M. Gadgeel, Nathan A. Pennell, Mary Jo Fidler, Balazs Halmos, Philip Bonomi, James Stevenson, Bryan Schneider, Ammar Sukari, Jaclyn Ventimiglia, Wei Chen, Cathy Galasso, Antoinette Wozniak, Julie Boerner, Gregory P. Kalemkerian
Journal: Journal of Thoracic Oncology (2018)
Subtle skin changes that suggest severe disease
Authors: Juan Antonio Moreno, None Romero, Alba Alvarez, None Abella, Daniel Lorenzo, Ramon Grimalt
Journal: BMJ (2018)

A 53 year old woman presented to the dermatology department with insect bites to the dorsum of the hands. On examination, yellow skin lesions were found on both sides of her neck (fig 1). The lesions, which were confluent papules 2-4 mm in diameter, had appeared several years before. The woman had no other symptoms.

She was taking duloxetine and clonazepam for depression, and dexketoprofen, calcium, and vitamin D supplements for chronic cervical spine pain.

The patient did not recall any other similar cases of skin lesions in her family.



### 1. What condition has caused the coalescent yellow papules?

#### Short answer

Pseudoxanthoma elasticum (PXE), a genetic disease causing yellowish papular lesions and redundant folds in flexural areas.

#### Discussion

PXE is an autosomal recessive disease caused by a mutation in gene ABCC6 on chromosome 16, which affects the connective tissue, causing ectopic mineralisation and fragmentation of elastic fibres.1 The term “pseudoxanthoma elasticum” was coined to indicate that the yellowish papules of PXE differed from authentic xanthomas (skin lesions caused by the accumulation of fat in macrophage cells) and to indicate that PXE papules are related to elastic tissue fragmentation.

Primary PXE skin lesions are yellowish papules 1 to 5 mm in …
A mutation in transcription factor MAFB causes Focal Segmental Glomerulosclerosis with Duane Retraction Syndrome
Authors: Yoshinori Sato, Hiroyasu Tsukaguchi, Hiroyuki Morita, Koichiro Higasa, Mai Thi Nhu Tran, Michito Hamada, Toshiaki Usui, Naoki Morito, Shoichiro Horita, Takao Hayashi, Junko Takagi, Izumi Yamaguchi, Huan Thanh Nguyen, Masayo Harada, Kiyoko Inui, Yuichi Maruta, Yoshihiko Inoue, Fumihiko Koiwa, Hiroshi Sato, Fumihiko Matsuda, Shinya Ayabe, Seiya Mizuno, Fumihiro Sugiyama, Satoru Takahashi, Ashio Yoshimura
Journal: Kidney International (2018)
Trump’s proposals would restrict US abortions and deny sexual health services for millions
Authors: Janice Hopkins Tanne
Journal: BMJ (2018)

Family planning clinics that receive federal funds through the Title X program would be required to establish “clear financial and physical separation” between their family planning services and their abortion services, under plans to restrict abortions in the US announced by the Trump administration.1

Speaking at a dinner for an anti-abortion group, President Donald Trump said, “My administration has proposed a new rule to prohibit Title X funding from going to any clinic that provides abortions.”

The proposal is aimed at Planned Parenthood, an organization that provides a broad range of health services to about 2.4 million, mostly poor, US patients. Much of its funding comes from the federal Title X family planning program, which provides comprehensive …
Nivolumab (Nivo) vs investigator’s choice (IC) in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): Efficacy and safety in CheckMate 141 by prior cetuximab use.
Authors: Robert L. Ferris, Lisa Licitra, Jérôme Fayette, Caroline Even, George R. Blumenschein, Kevin Harrington, Joel Guigay, Everett E. Vokes, Nabil F. Saba, Robert I. Haddad, Shanmugasundaram Ramkumar, Jeffrey Russell, Peter Brossart, Makoto Tahara, Manish Monga, Jin Zhu, A. Dimitrios Colevas, Maura L. Gillison
Journal: Journal of Clinical Oncology (2017)

6020 Background: In CheckMate 141, nivo resulted in significantly prolonged overall survival (OS), favorable safety, and stable quality of life vs IC in patients (pts) with platinum-refractory (PR) R/M SCCHN. Cetuximab, a formal trial stratification factor, permits exploratory subgroup assessment. Outcomes by prior cetuximab use are described. Methods: CheckMate 141 was a randomized, open-label, phase 3 trial (NCT02105636) in which pts (N = 361) with PR R/M SCCHN were randomized 2:1 and stratified by prior cetuximab use to nivo 3 mg/kg every 2 weeks or IC of methotrexate, docetaxel, or cetuximab. The primary endpoint was OS; additional endpoints were progression-free survival (PFS), objective response rate (ORR), and safety. A multivariate analysis will explore influence of additional factors. Results: Nivo improved OS vs IC regardless of prior cetuximab, and improvement was greater in pts without prior cetuximab (Table). Median OS was longer for nivo vs IC in pts with PD-L1 expression ≥ 1% regardless of prior cetuximab, and in pts with PD-L1 expression &lt; 1% without prior cetuximab. Among pts with PD-L1 expression ≥ 1%, ORR was higher with nivo vs IC with/without prior cetuximab. PFS was similar regardless of prior cetuximab. Grade 3–4 treatment-related adverse event rates for nivo vs IC were 11.7% vs 40.9% with prior cetuximab and 15.4% vs 26.7% without prior cetuximab. Conclusions: OS and ORR improved with nivo vs IC regardless of prior cetuximab use, and the magnitude of benefit was greater in pts without prior cetuximab exposure. These results support the use of nivo for R/M SCCHN regardless of prior cetuximab use. Clinical trial information: NCT02105636. [Table: see text]
Cannabinoids Derivatives Exert a Potent Antileukemic Effect By Modifying the Pattern of Membrane Sphingolipids
Authors: Mayte Medrano, María Victoria Barbado-Gonzalez, Nuria Campillo, Francisco Hidalgo, Teresa Caballero-Velazquez, Olga Perez-Lopez, Maria Sole-Rodriguez, Jose Ignacio Piruat-Palomo, Jose A. Perez-Simon
Journal: Blood (2016)
Comment on Buckley et al. Intensive Versus Standard Blood Pressure Control in SPRINT-Eligible Participants of ACCORD-BP. Diabetes Care 2017;40:1733–1738
Authors: Michael Y. Mi, Kenneth J. Mukamal
Journal: Diabetes Care (2018)

Buckley et al. (1) suggest that Systolic Blood Pressure Intervention Trial (SPRINT)-eligible patients from the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) trial who did not receive intensive glycemic control may have benefited from intensive blood pressure (BP) control and that therefore the studies share consistent results. Here, we report results of a similar analysis comparing SPRINT and ACCORD with a different conclusion. We specifically address whether varying patient characteristics between the trials account for the clear benefit of intensive BP control in SPRINT and the lack of benefit in ACCORD.

We compared SPRINT-eligible ACCORD patients with ACCORD-eligible SPRINT patients by applying the inclusion and exclusion criteria from both trials to each other (2,3). Of note, we excluded those with a history of stroke and used the Framingham 10-year cardiovascular disease (CVD) risk calculator for eligibility (4). We then calculated propensity scores for the likelihood of being assigned to one trial over another …
Reducing Bacterial Infections and Biofilm Formation Using Nanoparticles and Nanostructured Antibacterial Surfaces
Authors: Gujie Mi, Di Shi, Mian Wang, Thomas J. Webster
Journal: Advanced Healthcare Materials (2018)

With the rapid spreading of resistance among common bacterial pathogens, bacterial infections, especially antibiotic-resistant bacterial infections, have drawn much attention worldwide. In light of this, nanoparticles, including metal and metal oxide nanoparticles, liposomes, polymersomes, and solid lipid nanoparticles, have been increasingly exploited as both efficient antimicrobials themselves or as delivery platforms to enhance the effectiveness of existing antibiotics. In addition to the emergence of widespread antibiotic resistance, of equal concern are implantable device-associated infections, which result from bacterial adhesion and subsequent biofilm formation at the site of implantation. The ineffectiveness of conventional antibiotics against these biofilms often leads to revision surgery, which is both debilitating to the patient and expensive. Toward this end, micro- and nanotopographies, especially those that resemble natural surfaces, and nonfouling chemistries represent a promising combination for long-term antibacterial activity. Collectively, the use of nanoparticles and nanostructured surfaces to combat bacterial growth and infections is a promising solution to the growing problem of antibiotic resistance and biofilm-related device infections.
Latanoprostene Bunod Ophthalmic Solution 0.024%: A Review in Open-Angle Glaucoma and Ocular Hypertension
Authors: Sheridan M. Hoy
Journal: Drugs (2018)

Latanoprostene bunod ophthalmic solution 0.024% (hereafter referred to as latanoprostene bunod 0.024%) [Vyzulta™] is a nitric oxide (NO)-donating prostaglandin F2α analogue approved in the USA for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension. It is thought to lower IOP by increasing aqueous humour outflow through the uveoscleral pathway (mediated by latanoprost acid) and increasing the facility of aqueous humour outflow through the trabecular meshwork pathway (mediated by NO). Results from two multinational, phase III studies (APOLLO and LUNAR) and a pooled analysis of these studies demonstrated the noninferiority of latanoprostene bunod 0.024% to timolol ophthalmic solution 0.5% (hereafter referred to as timolol 0.5%) in terms of IOP-lowering efficacy over 3 months in patients with OAG or ocular hypertension, with the superiority of latanoprostene bunod 0.024% over timolol 0.5% subsequently demonstrated in APOLLO and the pooled analysis. Moreover, there was no apparent loss of IOP-lowering effect in subsequent safety extension periods of up to 9 months. The IOP-lowering efficacy seen in APOLLO and LUNAR was confirmed in a phase III study (JUPITER) in Japanese patients, with IOP reductions observed early (week 4) and maintained over the longer-term (12 months). Latanoprostene bunod 0.024% was well tolerated over up to 12 months in these studies, with most ocular treatment-emergent adverse events (TEAEs) being mild to moderate in severity. Thus, current evidence indicates once-daily latanoprostene bunod 0.024% is an effective and well tolerated treatment option for the reduction of IOP in adults with OAG or ocular hypertension.
qSOFA Score for Patients With Sepsis in Low- and Middle-Income Countries
Authors: Neill K. J. Adhikari, Gordon D. Rubenfeld
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
Multi-omic molecular profiling of lung cancer in COPD
Authors: Brian J. Sandri, Adam Kaplan, Shane W. Hodgson, Mark Peterson, Svetlana Avdulov, LeeAnn Higgins, Todd Markowski, Ping Yang, Andrew H. Limper, Timothy J. Griffin, Peter Bitterman, Eric F. Lock, Chris H. Wendt
Journal: European Respiratory Journal (2018)

Chronic obstructive pulmonary disease (COPD) is a known risk factor for developing lung cancer but the underlying mechanisms remain unknown. We hypothesise that the COPD stroma contains molecular mechanisms supporting tumourigenesis. We conducted an unbiased multi-omic analysis to identify gene expression patterns that distinguish COPD stroma in patients with or without lung cancer. We obtained lung tissue from patients with COPD and lung cancer (tumour and adjacent non-malignant tissue) and those with COPD without lung cancer for profiling of proteomic and mRNA (both cytoplasmic and polyribosomal). We used the Joint and Individual Variation Explained (JIVE) method to integrate and analyse across the three datasets. JIVE identified eight latent patterns that robustly distinguished and separated the three groups of tissue samples (tumour, adjacent and control). Predictive variables that associated with the tumour, compared to adjacent stroma, were mainly represented in the transcriptomic data, whereas predictive variables associated with adjacent tissue, compared to controls, were represented at the translatomic level. Pathway analysis revealed extracellular matrix and phosphatidylinositol-4,5-bisphosphate 3-kinase–protein kinase B signalling pathways as important signals in the tumour adjacent stroma. The multi-omic approach distinguishes tumour adjacent stroma in lung cancer and reveals two stromal expression patterns associated with cancer.
Abstract A51: Nicotine induces cervical lymph node metastasis of mouse tongue cancer by regulating Prx1 /EMT signaling
Authors: Min Wang, Wenwen Niu, Moci Qi, Xiaofei Tang
Journal: Cancer Research (2018)

Abstract Oral squamous cell carcinoma (OSCC) represents one of the most common malignant neoplasms worldwide, while tobacco is a major risk factor for OSCC. Nicotine has been reported to induce EMT and promote the progression in several malignant tumors. Our previous study showed that upregulation of Peroxiredoxin 1(PRX1) expression was observed and associated with nicotine-induced oxidative stress in OSCC. However, the effects of nicotine and the underlying molecular mechanisms on the development of OSCC metastases are not completely understood. Here, we established the cervical metastasis mouse models of tongue cancer by orthotopic transplantation of OSCC cell line siControl CAL 27 cells and siPRX1 CAL 27 cells labeled with GFP into the tongues of nude mice, in order to investigate the roles and mechanisms of nicotine in OSCC metastasis. Fluorescence stereomicroscopy was used to confirm the tumor formation and the development of cervical metastases, which the tumor cells showed distinct green fluorescence in mouse tongues and lymph nodes. The results showed that at day 13 after CAL 27 cell implantation, nicotine promoted OSCC growth in the tongues and metastatic rates of cervical lymph node in mice compared with control. Histologic examination and immunohistochemical staining with anti-keratin antibody further confirmed tumor formation and lymph node metastases. Nicotine treatment was shown to promote the downregulation of expression levels of E-cadherin, and upregulation of vimentin and Snail expression in tongues and lymph nodes, compared with those in the control mice. PRX1 knockdown led to the reduction in the metastasis rate, upregulation of E-cadherin expression, and downregulation of vimentin and Snail expression in tongues and lymph nodes. No significant differences were seen in the cervical lymph node metastatic rates and the expression of EMT-related markers between nicotine-treated and vehicle-treated mice after PRX1 knockdown. These results suggest that nicotine may induce cervical lymph node metastases through the regulation of Prx1/EMT signal pathway during OSCC pathogenesis. PRX1 plays a critical role in nicotine-induced metastasis of OSCC. Citation Format: Min Wang, Wenwen Niu, Moci Qi, Xiaofei Tang. Nicotine induces cervical lymph node metastasis of mouse tongue cancer by regulating Prx1 /EMT signaling [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A51.
Abstract IA03: Cancer modeling in the CRISPR age
Authors: Andrea Ventura
Journal: Cancer Research (2018)

Abstract The widespread use of high-throughput genomic methods is profoundly changing the way we understand, classify, and treat cancers, and provides unprecedented opportunities to design therapeutic approaches tailored to individual patients. The success of these efforts is contingent on our ability to identify, among the hundreds of different genetic lesions, those that actively drive tumorigenesis. The recent development of powerful genome editing methods promises to greatly speed up this process and allows us, for the first time, to model a wide range of previously inaccessible cancer-associated mutations. I will discuss how CRISPR-based gene editing methods are revolutionizing cancer. I will also show how my group is combining computational methods and in vivo somatic genome editing approaches to generate and characterize novel mouse models of human cancers and to explore the noncoding fraction of the cancer genome. Citation Format: Andrea Ventura. Cancer modeling in the CRISPR age [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr IA03.
SP0115 Crystals and joints
Authors: M Doherty
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> Primary metabolic disease may predispose to the deposition of a variety of crystals in and around joints, most notably calcium pyrophosphate (CPPD) and apatite. Crystal associated musculoskeletal symptoms may be the presentation of such disease. Renal failure additionally predisposes to urate and oxalate crystal deposition. In most disease states the principal mechanisms relate to elevated ionic products. There is good evidence that hyperparathyroidism, hypomagnesaemia, haemochromatosis and hypophosphatasia predispose to CPPD deposition; data are less convincing for hypothyroidism, Wilson’s disease and other putative associations. Clinical features are acute “pseudogout” attacks in association with polyarticular chondrocalcinosis (CC). Haemochromatosis is exceptional in additionally causing structural joint change and chronic symptoms. Patients &lt;55 years presenting with recurrent acute attacks and polyarticular CC should be screened for metabolic disease (minimum = serum ferritin, magnesium, calcium, alkaline phosphatase). Treatment of the primary disease, however, probably little influences the outcome of CPPD and CC. All these diseases increase extracellular pyrophosphate levels; effects on CPPD crystal nucleation and dissolution, however, are also evident. Rare monogenic familial CC may shortly be explained as primary metabolic disorders of pyrophosphate metabolism involving several enzyme systems. Milder forms of hypophosphatasia may cause calcific periarthritis due to apatite deposition, in association with axial and peripheral ossifying enthesopathy. Hyperparathyroidism (primary, but particularly secondary or tertiary in patients with renal failure) may also cause this. With renal failure crystal deposits may be massive (“tumoral calcinosis”) and both form and resolve with treatment over short periods of time. By far the more common consequence of renal failure, however, is urate crystal deposition. This may result in chronic tophaceous gout and acute attacks. Treatment may prove difficult but allopurinol remains the principal agent. Oxalate crystals can deposit in many tissues, including muscles and joints, and possibly cause myalgia and acute inflammatory episodes in chronic dialysis patients. <h3>Reference</h3> Jones A, <i>et al</i>. Diseases associated with CPPD deposition disease. Semin Arthritis Rheum 1992;22:188–202
Image Gallery: Molluscum contagiosum-like facial lesions in a patient with a renal transplant: deep dermatophytosis due to <i>Trichophyton rubrum</i>
Authors: E.N. Ergen, S.L. Donaldson, M.S. Stratton, P.G. Pavlidakey, B.E. Elewski
Journal: British Journal of Dermatology (2018)