tbuckley/cabot-search huggingface dataset:
Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial
Authors: Marc A Riedl, Vesna Grivcheva-Panovska, Dumitru Moldovan, James Baker, William H Yang, Bruno M Giannetti, Avner Reshef, Sladjana Andrejevic, Richard F Lockey, Roman Hakl, Shmuel Kivity, Joseph R Harper, Anurag Relan, Marco Cicardi
Journal: The Lancet (2017)
Risk Factors for Melanoma in Renal Transplant Recipients
Authors: Mona Ascha, Mustafa S. Ascha, Joseph Tanenbaum, Jeremy S. Bordeaux
Journal: JAMA Dermatology (2017)

Melanoma risk factors and incidence in renal transplant recipients can inform decision making for both patients and clinicians.To determine risk factors and characteristics of renal transplant recipients who develop melanoma.This cohort study of a large national data registry used a cohort of renal transplant recipients from the United States Renal Data System (USRDS) database from the years 2004 through 2012. Differences in baseline characteristics between those who did and did not develop melanoma were examined, and a survival analysis was performed. Patients with renal transplants who received a diagnosis of melanoma according to any inpatient or outpatient claim associated with a billing code for melanoma were included. A history of pretransplant melanoma, previous kidney transplantation, or transplantation after 2012 or before 2004 were exclusion criteria. The data analysis was conducted from 2015 to 2016.Receipt of a renal transplant.Incidence and risk factors for melanoma.Of 105 174 patients (64 151 [60.7%] male; mean [SD] age, 49.6 [15.3] years) who received kidney transplants between 2004 and 2012, 488 (0.4%) had a record of melanoma after transplantation. Significant risk factors for developing melanoma vs not developing melanoma included older age among recipients (mean [SD] age, 60.5 [10.2] vs 49.7 [15.3] years; P < .001) and donors (42.6 [15.0] vs 39.2 [15.1] years; P < .001), male sex (71.5% vs 60.7%; P < .001), recipient (96.1% vs 66.5%; P < .001) and donor (92.4% vs 82.9%; P < .001) white race, less than 4 HLA mismatches (44.9% vs 37.1%; P = .001), living donors (44.7% vs 33.7%; P < .001), and sirolimus (22.3% vs 13.2%; P < .001) and cyclosporine (4.9% vs 3.2%; P = .04) therapy. Risk factors significant on survival analysis included older recipient age (hazard ratio [HR] per year, 1.06; 95% CI, 1.05-1.06; P < .001), recipient male sex (HR, 1.53; 95% CI, 1.25-1.88; P < .001), recipient white race, living donors (HR, 1.35; 95% CI, 1.11-1.64; P = .002), and sirolimus (HR, 1.54; 95% CI, 1.22-1.94; P < .001) and cyclosporine (HR, 1.93; 95% CI, 1.24-2.99; P = .004) therapy. The age-standardized relative rate of melanoma in USRDS patients compared with Surveillance, Epidemiology, and End Results patients across all years was 4.9. A Kaplan-Meier estimate of the median time to melanoma among those patients who did develop melanoma was 1.45 years (95% CI, 1.31-1.70 years).Renal transplant recipients had greater risk of developing melanoma than the general population. We believe that the risk factors we identified can guide clinicians in providing adequate care for patients in this vulnerable group.
Giant-Cell Arteritis — More Ecstasy, Less Agony
Authors: David B. Hellmann
Journal: New England Journal of Medicine (2017)

If Irving Stone had written a book about giant-cell arteritis rather than about Michelangelo, he might have chosen The Ecstasy and the Agony as the more appropriate title. As many physicians know, diagnosing giant-cell arteritis and witnessing the patient's dramatic initial response to treatment are much more fulfilling than managing a disease that lasts for months or years and that leads to the use of glucocorticoids in doses that result in a litany of side effects, including weight gain, hypertension, diabetes, and osteoporosis. This vexing challenge of treating giant-cell arteritis explains why doctors and patients will welcome the results of . . .
Abstract 361: Loss of Cardiac Retinoic Acid Receptor Alpha Promotes Diastolic Heart Failure With Preserved Ejection Fraction
Authors: Sen Zhu, Rakeshwar Guleria, Candice Thomas, Fnu Gerilechaogetu, Amanda Roth, Rajesh Kumar, David Dostal, Kenneth Baker, Jing Pan
Journal: Circulation Research (2015)

Objectives: We have previously demonstrated that the expression/activation of retinoic acid receptor (RAR) is inhibited in diabetic hearts, and that activation of RARα prevents diabetes-induced diastolic heart failure, suggesting that impairment of RARα signaling may be a critical mechanism in heart failure. Methods and Results: Cardiac RARα gene deletion (KO) was achieved by tamoxifen injection at 6-weeks old RARαfl/fl α-MHC-MerCreMer mice, RARαfl/fl mice were used as control (WT). Heart function was monitored by echocardiograph for 64 wks. Mice were sacrificed at 20 or 64 wks post gene deletion, respectively. A significant decrease in E/A ratio and TDI E’ and increase in IVRT (isovolumic relaxation time) and DT (deceleration time) suggested diastolic dysfunction after 16 wks of gene deletion in KO mice, which was confirmed by cardiac catheterization (decreased dP/dtmin and increased tau). Concentric hypertrophy developed in KO mice after 56 wks of gene deletion, as confirmed by increased thickness of left ventricular wall and interventricular septum and elevated heart weight/tibia length ratio. However, no significant difference was observed in LVEF (LV ejection fraction), FS (fraction shortening) and dP/dtmax between KO and WT mice. Significantly increased gene expression of NOX2 (NADPH oxidase 2) and NOX4, decreased SOD1 and SOD2 levels and increased intracellular reactive oxygen species (ROS) were observed in KO mouse hearts, along with a significantly decreased protein expression of SERCA2a and CaMKIIδ, decreased phosphorylation of PLB, Akt and CaMKIIδ. Overexpression of RARα in cardiomyocytes rescued RARα deletion-induced changes in SERCA2a, PLB, Akt and CaMKIIδ. Deletion of RARα in cardiomyocytes impaired intracellular calcium reuptake into SR and cardiomyocyte relaxation. Inhibition of ROS by N-acetyl cysteine abolished RARα deletion-induced calcium mishandling and cardiomyocyte relaxation. Conclusion: Cardiac specific deletion of RARα induces diastolic heart failure with preserved ejection fraction (HFpEF), by promoting intracellular ROS and disrupting SERCA2a-mediated calcium reuptake and cardiomyocyte relaxation. Our study suggests that deficiency in RARα signaling is a novel mechanism leading to HFpEF.
Legalization of Same-Sex Marriage and Drop in Adolescent Suicide Rates: Association But Not Causation—Reply
Authors: Julia Raifman, Ellen Moscoe, S. Bryn Austin
Journal: JAMA Pediatrics (2017)

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 Pediatrics 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 Pediatrics journal
Crosstalk between Aurora-A and p53: frequent deletion or downregulation of Aurora-A in tumors from p53 null mice
Authors: Jian-Hua Mao, Di Wu, Jesus Perez-Losada, Tao Jiang, Qian Li, Richard M Neve, Joe W Gray, Wei-Wen Cai, Allan Balmain
Journal: Clinical Cancer Research (2007)

A78   The  Aurora-A  kinase gene is amplified in a subset of human tumors. Inhibitors of the Aurora-A kinase have been developed by several pharmaceutical companies as potential cancer therapeutics, based on the known oncogenic activities of this gene in induction of genetic instability and cell transformation. Array CGH analysis of radiation-induced lymphomas from  p53  heterozygous mice demonstrates that these tumors show considerable genetic instability, including frequent amplification or gene copy number gains at the  Aurora-A  locus. In contrast, similar tumors from  p53  null mice show less genetic instability, and a substantial subset had heterozygous deletions of  Aurora-A . Loss of one copy of the  Aurora-A  gene, and/or low protein levels, are also found in some human breast cancer cell lines. Down-regulation of Aurora-A levels in  p53  null MEFs by RNAi induced a selective growth advantage, whereas similar treatment of  p53 +/- MEFs induced slower growth. Prolonged downregulation of Aurora-A in  p53 +/- MEFs led to early loss of the wild type  p53  gene, demonstrating an important functional crosstalk between these pathways. We conclude that there is an important functional interaction  in vivo  between p53 and Aurora kinase, and that this network should be taken into account in the design of clinical trials of these agents for cancer therapy.
The United States Presidents Emergency Plan for AIDS Relief. Report on food and nutrition for people living with HIV / AIDS.
Authors: Suich A, Zhao Hx, Zhang Fj, Han N, Lan, Yao J, Cao Yz, Jaime Pc, Florindo Aa, Latorre, Segurado Aa, van Leeuwen E, Prins Jm, Jurriaans S, Boer K, Reiss P, Simelela Pn
Journal: Human Reproduction Update (2006)

According to the World Health Organization (WHO) nutritional support is an integral part of a comprehensive response to HIV/AIDS. There is evidence that nutrient intake can improve antiretroviral absorption and tolerance. Receiving appropriate nutrition can help improve the health and quality of life of HIV-infected individuals. Individuals who receive antiretroviral therapy (ART) with appropriate nutrition are more likely to regain weight and more likely to adhere to their medications thus helping them rejoin the work force and improve food security for themselves and their families. This document presents a U.S. Government (USG)- wide approach for addressing food and nutrition needs of PLWHA receiving treatment and care. Recognizing that this is too large and complex a problem for any one agency to handle on its own the Office of the Global AIDS Coordinator (OGAC) is partnering with other U.S. government agencies including the U.S. Agency for International Development (USAID) the U.S. Department of Agriculture(USDA) the U.S. Department of Health and Human Services (HHS) and the Peace Corps as well as relevant UN agencies and the private sector to leverage resources to carry out supplementary feeding micronutrient supplementation and food security and livelihood support. Through partnerships PEPFAR addresses the needs of HIV-affected communities especially affected families and caregivers of PLWHA. Furthermore PEPFAR are strengthens coordination at the country level in order to facilitate the implementation of these programs and to improve monitoring and evaluation. (excerpt)
Gastroresistant oral peptide for fluorescence imaging of colonic inflammation
Authors: Paola Luciani, Ander Estella-Hermoso de Mendoza, Tommaso Casalini, Silvia Lang, Kirstin Atrott, Marianne R. Spalinger, Anna Pratsinis, Jens Sobek, Isabelle Frey-Wagner, Jens Schumacher, Jean-Christophe Leroux, Gerhard Rogler
Journal: Journal of Controlled Release (2017)
Treatment of hidradenitis suppurativa with rifampicin: have we forgotten tuberculosis?
Authors: P. Mendes-Bastos, R. Macedo, R. Duarte
Journal: British Journal of Dermatology (2017)

DEAR EDITOR, Hidradenitis suppurativa (HS) is a chronic, recurrent and debilitating skin disease of the hair follicle that is accompanied by systemic inflammation.Treating HS is challenging, and therapeutic tools as diverse as topical and systemic antibiotics, biologics, intralesional steroids, surgical procedures or light and laser therapies are frequently needed.The combination of oral clindamycin and rifampicin has been suggested as a possible treatment regimen.
RNA profiling of desmoplastic small round cell tumors (DSRCTs) using next-generation sequencing.
Authors: Pooja Hingorani, Troy McEachron, Jin Park, Jason Steel, Julie M Gastier-Foster, Carlos Rodriguez-Galindo, Stephen Skapek, Douglas S. Hawkins, Joshua LaBaer, Valentin Dinu
Journal: Journal of Clinical Oncology (2016)

10552 Background: DSRCT is a rare malignant tumor that predominantly affects males in their second decade of life. Most commonly, it presents as diffuse abdomino-pelvic disease. Despite intense multi-modal therapy, the 5-year overall survival remains dismal at less than 20%. Histologically, DSRCT displays multi-lineage commitment including epithelial, neuronal and myogenic differentiation, thereby confounding attempts to identify the cell of origin. Presently, the defining molecular marker of DSRCT is the t(11;22)(p13;q12) translocation encompassing EWSR1 and WT1. Other investigations elucidating the genomic and/or transcriptomic landscape of this disease have yet to be reported. In this study we have analyzed the gene expression profile of a cohort of DSRCTs using next-generation RNA sequencing. Methods: RNA from DSRCT tumor samples were obtained from Cooperative Human Tissue Network biorepository after histological confirmation of disease. RNA sequencing was completed using the Illumina HiSeq 2000 sequencing system. Presence of the EWSR1-WT1fusion was verified using both RNA-sequencing and PCR. Principal component analysis (PCA) was performed using available gene expression datasets from various normal tissues (Illumina Body Map) and tumor tissues (TCGA). Results: We analyzed 14 tumor RNA samples out of which two were confirmed negative for the EWSR1-WT1translocation. Hierarchical clustering suggested that fusion-negative and fusion-positive DSRCTs are molecularly different. Nonetheless, PCA revealed that both fusion-positive and fusion-negative DSRCT samples clustered close together independently of other normal tissues. They did cluster close to other sarcomas. Hierarchical clustering also revealed molecular heterogeneity within the fusion-positive DSRCT samples. Conclusions: A small proportion of DSRCTs can be negative for the EWS-WT1 fusion suggesting that there may be other fusion-independent mechanisms that drive the common phenotypic and clinical aspects of DSRCT. While the cell of origin for DSRCT remains elusive, DSRCT gene expression profile is similar to other soft-tissue sarcomas. Further analysis is ongoing.
Impact of molecular prescreening for genomically-guided trials in head and neck cancer (HNC).
Authors: Neus Baste, Irene Brana, David Viros, Jorge Pamias, Juan Lorente, Jordi Giralt, Coro Bescos, Margarita Alberola, Ana Vivancos, Paolo Nuciforo, Rodrigo Dienstmann, Josep M. del Campo, Josep Tabernero, Enriqueta Felip, Jordi Rodón
Journal: Journal of Clinical Oncology (2016)

6030 Background: HNC encompass a group of highly heterogeneous diseases, including oral, oropharyngeal and laryngeal squamous cell carcinomas (SCC), nasopharyngeal (NP), nasosinusal (NS) and salivary gland (SG) tumors. Chemotherapy has shown limited efficacy in recurrent (rec)/metastatic (met) disease. Genomic studies have increased our understanding of HNC biology, identifying potential targetable mutations (mut). We evaluated the impact of precision medicine efforts in HNC at Vall d’Hebron Institute of Oncology (VHIO). Methods: From 10/2010 to 10/2015, 49 patients (pts) with metastatic HNC underwent tumor molecular profiling at VHIO. Mut detection was performed using multiplex mass-spectrometry (Sequenom, n = 21) or NGS (AmpliconSeq, n = 28).Profiling was performed on metastatic (n = 21) or primary sites (n = 19), with missing information in remaining cases (n = 9). Results: Most frequent tumor type was SCC (n = 20), followed by SG (n = 18), NP (n = 9) and NS (n = 2). Median age at diagnosis was 51 years, 55% stage IV. Rec/met disease to nodes or lungs was seen in 95% of SCC, while liver met was detected in 33% NP and 39% SG. PIK3CA (5/49) and CDKN2A mut (5/28) were found across all subtypes. TP53 mut were enriched in SCC (8/9, p < 0.001). SG had PTEN (1/10), NF1 (1/3), HRAS (3/18), ERBB3 (1/10) and NRAS (1/18) mut. One NP harbored NRAS mut (1/9). The prevalence of targetable mut varied according to tumor type (44% SG, 15% SCC, 36% N/NS; p = 0.03). In total, 18/49 pts were enrolled into 26 phase 1 trials (ph1), 37% accrual rate. Median prior treatment lines were 2 (0-5). 9/26 ph1 were matched therapies (mTher): 6 in SG (PIK3CA, PTEN or ERBB3 mut), 2 in SCC (CDKN2A or PTEN mut) and 1 in NP (NRAS mut). Stable disease was observed in 5 SG treated with PI3K pathway inhibitors (inh), and 1 partial response in the NP treated with PI3K plus MEK inh. Considering pts as their own controls, median time to treatment failure (TTF) during mTher (9 months, range 3-23) was similar to TTF while on prior first / second treatment line (6.9 months, range 4-110; p = 0.68). Conclusions: Genomic characterization of HNC identifies pts likely to benefit from a mTher in ph1, with promising targets being PI3K pathway mut in SG and NRAS mut in NP.
Delafloxacin: First Global Approval
Authors: Anthony Markham
Journal: Drugs (2017)

Delafloxacin (Baxdela™) is a fluoroquinolone antibacterial with activity against both gram-positive and gram-negative pathogens being developed by Melinta Therapeutics. The drug is being investigated or considered as a treatment for various bacterial infections and in June 2017 received approval in the USA for the treatment of acute bacterial skin and skin structure infections. This article summarizes the milestones in the development of delafloxacin leading to this first global approval for the treatment of acute bacterial skin and skin structure infections.
Multicenter randomized phase II study comparing alternate-day oral therapy using S-1 with the standard regimen as a first-line treatment for patients with locally advanced and metastatic pancreatic cancer: PAN-01 study.
Authors: Masayuki Sho, Atsushi Shimizu, Hiroaki Yanagimoto, Shoji Nakamori, Takuji Okusaka, Hiroshi Ishii, Masayuki Kitano, Kazuya Sugimori, Hiroyuki Maguchi, Shinichi Ohkawa, Hiroshi Imaoka, Daisuke Hashimoto, Kazuki Ueda, Hiroko Nebiki, Tatsuya Nagakawa, Hiroyuki Isayama, Yasuhiro Hagiwara, Yasuo Ohashi, Tetsuhiko Shirasaka, Hiroki Yamaue
Journal: Journal of Clinical Oncology (2016)

4107 Background: S-1 is an active agent for the treatment of pancreatic cancer. GEST study has previously shown the noninferiority of S-1 to gemcitabine in advanced pancreatic cancer. However, the standard regimen of 4 weeks of administration followed by 2 weeks of rest frequently causes adverse effects. To induce the effect of S-1 while reducing toxicity, alternate-day administration may be a treatment option. The aim of this study was to clarify the efficacy and toxicity of alternate-day administration of S-1 compared to the standard regimen for advanced pancreatic cancer. To this end, we conducted multicenter randomized phase II study, PAN-01. Methods: Patients who met the study criteria, including histological confirmation, age > 20, Performance Status of 0 or 1, no prior chemotherapy/radiotherapy, and adequate organ functions, were randomly assigned at a ratio of 1:2 to standard daily administration (Arm A) or alternate-day administration (Arm B). The primary end point was overall survival (OS). Secondary end points were safety, response rate, progression-free survival (PFS), and time to treatment failure. Results: A total of 190 patients were enrolled and 185 were subject to final analysis (Arm A: 64, Arm B: 121). The median OS for Arms A and B were 10.4 and 9.4 months, respectively (hazard ratio, 1.19; 95% CI, 0.86-1.64). Data did not indicate the noninferiority of alternate-day administration to standard regimen in overall survival. Furthermore, the median PFS were 4.2 and 3.0 months, respectively (hazard ratio, 1.65; 95% CI, 1.20-2.29), indicating that alternate-day administration was significantly worse than standard regimen in tumor progression. Anorexia (all grade: Arm A vs Arm B (%): 58.5 vs 50.0, P = 0.04), fatigue (60.0 vs 42.6, P = 0.02), pigmentation (24.6 vs 7.4, P < 0.001) and pneumonitis (7.7 vs 1.6, P = 0.03) were more common in daily administration than alternate-day administration. Conclusions: This study failed to demonstrate the noninferiority of alternate-day administration of S-1 to standard regimen as a first-line chemotherapy in unresectable pancreatic cancer. Clinical trial information: UMIN000008604.
Borealis-1: a randomized, first-line, placebo-controlled, phase II study evaluating apatorsen and chemotherapy for patients with advanced urothelial cancer
Authors: J. Bellmunt, B.J. Eigl, E. Senkus, Y. Loriot, P. Twardowski, D. Castellano, N. Blais, S.S. Sridhar, C.N. Sternberg, M. Retz, S. Pal, B. Blumenstein, C. Jacobs, P.S. Stewart, D.P. Petrylak
Journal: Annals of Oncology (2017)
INNOVATE: A phase II study of TTFields (200 kHz) concomitant with weekly paclitaxel for recurrent ovarian cancer—Updated safety and efficacy results.
Authors: Ignace Vergote, Roger von Moos, Luis Manso, Cristiana Sessa
Journal: Journal of Clinical Oncology (2017)

5580 Background: TTFields are a non-invasive, regional antimitotic treatment modality, which have been approved for the treatment of recurrent and newly diagnosed glioblastoma by the FDA. TTFields act by delivering intermediate frequency alternating electric fields to the tumor, predominantly by disrupting the formation of the mitotic spindle during metaphase. INNOVATE was the first trial testing TTFields (200kHz) in ovarian cancer patients. Methods: Thirty-one recurrent, platinum-resistant, unresectable ovarian cancer patients were enrolled in the INNOVATE trial and treated with TTFields in combination with weekly paclitaxel. The primary endpoint was treatment emergent adverse events. Secondary endpoints included progression free-survival, overall survival and radiological response rate. Results: The median age was 60 (range – 45-77), most patients (77%) had serous histology. 52% had an ECOG score of 0. The median number of prior chemotherapy regimens was 4.1 (range 1-11). All patients were platinum-resistant, and 97% of patients received prior taxane-containing regimens. Ten (32%) patients suffered from serious adverse events (SAEs) during the study, none were related to TTFields. Of all reported SAEs, 31% were related to gastrointestinal disorders (ileus, jaundice and ascites) and 31% were respiratory events (dyspnea, pleural effusion and pulmonary embolism). Only one SAE which, related to the tumor, led to permanent discontinuation of the device. Most patients were reported to have mild-moderate, TTFields-related skin irritation, out of whom only two patients (6.4%) had severe-grade events. The median PFS was 8.9 months (95% CI 4.7, NA). Of the evaluable tumors, 25% had partial response and another 46.4% stable disease – a clinical benefit of 71.4%. Six patients (19.4%) had a CA 125 response, translating into a decrease of 50% or more in serum levels. The median OS was not reached. Conclusions: TTFields concomitant to weekly paclitaxel are tolerable and safe in heavily pre-treated platinum-resistant ovarian cancer ovarian cancer patients. These data support further clinical testing of TTFields with chemotherapy in ovarian cancer. Clinical trial information: NCT02244502.
Meta-analysis of genome-wide studies of psoriasis susceptibility reveals linkage to chromosome 6p21 and 4q28-q31 in caucasian and chinese hans population.
Authors: G S Sagoo, R Tazi-Ahnini, Jonathan Barker, J T Elder, R P Nair, L Samuelsson, H Traupe, Richard Trembath, D A Robinson, M M Iles
Journal: British Journal of Dermatology (2004)