tbuckley/cabot-search huggingface dataset:
Bisphosphonate Treatment Beyond 5 Years and Hip Fracture Risk in Older Women
Authors: Monika A. Izano, Joan C. Lo, Annette L. Adams, Bruce Ettinger, Susan M. Ott, Malini Chandra, Rita L. Hui, Fang Niu, Bonnie H. Li, Romain S. Neugebauer
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Clinical trials have demonstrated the antifracture efficacy of bisphosphonate drugs for the first 3 to 5 years of therapy. However, the efficacy of continuing bisphosphonate for as long as 10 years is uncertain. <h3>Objective</h3> To examine the association of discontinuing bisphosphonate at study entry, discontinuing at 2 years, and continuing for 5 additional years with the risk of hip fracture among women who had completed 5 years of bisphosphonate treatment at study entry. <h3>Design, Setting, and Participants</h3> This cohort study included women who were members of Kaiser Permanente Northern and Southern California, 2 integrated health care delivery systems, and who had initiated oral bisphosphonate and completed 5 years of treatment by January 1, 2002, to September 30, 2014. Data analysis was conducted from January 2018 to August 2020. <h3>Exposure</h3> Discontinuation of bisphosphonate at study entry (within a 6-month grace period), discontinuation at 2 years (within a 6-month grace period), and continuation for 5 additional years. <h3>Main Outcomes and Measures</h3> The outcome was hip fracture determined by principal hospital discharge diagnoses. Demographic, clinical, and pharmacological data were ascertained from electronic health records. <h3>Results</h3> Among 29 685 women (median [interquartile range] age, 71 [64-77] years; 17 778 [60%] non-Hispanic White individuals), 507 incident hip fractures were identified. Compared with bisphosphonate discontinuation at study entry, there were no differences in the cumulative incidence (ie, risk) of hip fracture if women remained on therapy for 2 additional years (5-year risk difference [RD], −2.2 per 1000 individuals; 95% CI, −20.3 to 15.9 per 1000 individuals) or if women continued therapy for 5 additional years (5-year RD, 3.8 per 1000 individuals; 95% CI, −7.4 to 15.0 per 1000 individuals). While 5-year differences in hip fracture risk comparing continuation for 5 additional years with discontinuation at 2 additional years were not statistically significant (5-year RD, 6.0 per 1000 individuals; 95% CI, −9.9 to 22.0 per 1000 individuals), interim hip fracture risk appeared lower if women discontinued after 2 additional years (3-year RD, 2.8 per 1000 individuals; 95% CI, 1.3 to 4.3 per 1000 individuals; 4-year RD, 9.3 per 1000 individuals; 95% CI, 6.3 to 12.3 per 1000 individuals) but not without a 6-month grace period to define discontinuation. <h3>Conclusions and Relevance</h3> In this study of women treated with bisphosphonate for 5 years, hip fracture risk did not differ if they discontinued treatment compared with continuing treatment for 5 additional years. If women continued for 2 additional years and then discontinued, their risk appeared lower than continuing for 5 additional years. Discontinuation at other times and fracture rates during intervening years should be further studied.
Duration of obesity exposure between ages 10 and 40 years and its relationship with cardiometabolic disease risk factors: A cohort study
Authors: Tom Norris, Tim J. Cole, David Bann, Mark Hamer, Rebecca Hardy, Leah Li, Ken K. Ong, George B. Ploubidis, Russell Viner, William Johnson
Journal: PLoS Medicine (2020)

Background Individuals with obesity do not represent a homogeneous group in terms of cardiometabolic risk. Using 3 nationally representative British birth cohorts, we investigated whether the duration of obesity was related to heterogeneity in cardiometabolic risk. Methods and findings We used harmonised body mass index (BMI) and cardiometabolic disease risk factor data from 20,746 participants (49.1% male and 97.2% white British) enrolled in 3 British birth cohort studies: the 1946 National Survey of Health and Development (NSHD), the 1958 National Child Development Study (NCDS), and the 1970 British Cohort Study (BCS70). Within each cohort, individual life course BMI trajectories were created between 10 and 40 years of age, and from these, age of obesity onset, duration spent obese (range 0 to 30 years), and cumulative obesity severity were derived. Obesity duration was examined in relation to a number of cardiometabolic disease risk factors collected in mid-adulthood: systolic (SBP) and diastolic blood pressure (DBP), high-density-lipoprotein cholesterol (HDL-C), and glycated haemoglobin (HbA1c). A greater obesity duration was associated with worse values for all cardiometabolic disease risk factors. The strongest association with obesity duration was for HbA1c: HbA1c levels in those with obesity for &lt;5 years were relatively higher by 5% (95% CI: 4, 6), compared with never obese, increasing to 20% (95% CI: 17, 23) higher in those with obesity for 20 to 30 years. When adjustment was made for obesity severity, the association with obesity duration was largely attenuated for SBP, DBP, and HDL-C. For HbA1c, however, the association with obesity duration persisted, independent of obesity severity. Due to pooling of 3 cohorts and thus the availability of only a limited number harmonised variables across cohorts, our models included adjustment for only a small number of potential confounding variables, meaning there is a possibility of residual confounding. Conclusions Given that the obesity epidemic is characterised by a much earlier onset of obesity and consequently a greater lifetime exposure, our findings suggest that health policy recommendations aimed at preventing early obesity onset, and therefore reducing lifetime exposure, may help reduce the risk of diabetes, independently of obesity severity. However, to test the robustness of our observed associations, triangulation of evidence from different epidemiological approaches (e.g., mendelian randomization and negative control studies) should be obtained.
Comprehensive characterization of the human pancreatic proteome for bioengineering applications
Authors: Amish Asthana, Riccardo Tamburrini, Deborah Chaimov, Carlo Gazia, Stephen J. Walker, Mark Van Dyke, Alice Tomei, Sandrine Lablanche, John Robertson, Emmanuel C. Opara, Shay Soker, Giuseppe Orlando
Journal: Biomaterials (2020)
Plasma exosomal <i>miR-375-3p</i> regulates mitochondria-dependent keratinocyte apoptosis by targeting XIAP in severe drug-induced skin reactions
Authors: Chen Zhang, ZhenLai Zhu, JiXin Gao, LuTing Yang, ErLe Dang, Hui Fang, Shuai Shao, ShaoLong Zhang, ChunYing Xiao, Xu Yuan, Wei Li, Riichiro Abe, HongJiang Qiao, Gang Wang, Meng Fu
Journal: Science Translational Medicine (2020)

Circulating exosomal miR-375-3p promotes keratinocyte apoptosis via XIAP repression in Stevens-Johnson syndrome and toxic epidermal necrolysis.
The Promise of Lifestyle Interventions in Individuals With Genetically Higher Risk for Obesity
Authors: Marie-France Hivert, Ann Chen Wu
Journal: JAMA Pediatrics (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
NIMG-35. IMPROVING CETCS MICRONEEDLE VISIBILITY IN A MAGNETIC RESONANCE IMAGING ENVIRONMENT
Authors: Brianna Morales, Jason Mehta, Christopher Rylander
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Annually, there are less than 20,000 cases of glioblastoma reported in the United States. This malignant tumor type has a survival rate of 5.6% and patient survival is approximately 14 months. The current standard of treatment is tumor resection, an attempt to remove the tumor; followed by, chemotherapy and radiation treatment. A newer form of treatment is convection-enhanced delivery (CED). Dr. Chris Rylander’s lab developed a novel method of CED, known as the convection-enhanced thermo-therapy catheter system (CETCS). The implementation of CETCS will be in an MRI environment, which calls for a need to improve the contrast of the needles against the native brain tissue. Increased contrast of the needles could improve remote control of the needles, and delivery of the drug. METHODS We evaluated several groups: (1) Control (water and air), (2) Nanomaterials in Polyimide Resin (Iron oxide nanoparticles and gadolinium oxide nanoparticles, some were contained in a polyetheretherketone tubing), and (3) Stainless Steel Wire (SS 316L). We cast needle groups into a 0.6% (w/w) Agarose phantom. Then, images were acquired with a 3T Siemens MRI and a 20-channel head coil in a series of 30 slices through the axial face of the phantom to the proximal face of the cube. Width analysis was conducted using Syngo FastView to determine the size of the artifacts in the MR images. RESULTS All modifications had a higher contrast than the controls, and the two largest artifacts measured were the SS 316L (4.9 ± 0.3 mm) and the iron oxide nanoparticles in the polyimide resin (3.5 ± 0.1 mm). An additional observation was the non-uniform shape of the two groups with the large artifacts. DISCUSSION Future iterations of these modifications need to be adjusted based on the desired artifact size, currently set to be at least 2 mm in diameter.
RTID-06. ENHANCING TUMOR TREATING FIELDS THERAPY FOR RECURRENT GLIOBLASTOMA WITH TARGETED AND INDIVIDUALIZED SKULL REMODELING SURGERY. A MULTI-CENTER RANDOMIZED PHASE 2 TRIAL
Authors: Nikola Mikic, Anders Korshøj
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND We present an upcoming(Sep. 2020) randomized, comparative, multi-center, investigator-initiated, interventional, phase 2 trial testing the efficacy of a novel therapeutic concept for recurrent glioblastoma(GBM). The intervention combines personalized targeted skull remodeling surgery(SR-surgery) with Tumor Treating Fields(TTFields) and best practice medical oncological therapy. SR-surgery involves strategically placed burr holes to strengthen the electric field in the tumor region. Preclinical studies indicate that SR-surgery provides a marked and focal enhancement(~100%) of TTFields. We recently concluded a phase 1 safety/feasibility study indicating promising clinical efficacy and no clinically significant toxicity related to the intervention. This subsequent randomized, comparative phase 2 trial aims to validate superior efficacy of the treatment. METHOD We will utilize a comparative, 1:1 randomized, minimax two-stage phase 2 design with an expected sample size of 70 patients, interim futility analysis at 1-yr follow-up of the first 52 patients and a maximum sample size of 84 patients. Patients will receive either 1)TTFields and best practice medical oncological treatment(control arm) or 2) SR-surgery plus TTFields and best practice medical oncological treatment (interventional arm). Major eligibility criteria include age ≥ 18 years, supratentorial GBM, Karnofsky performance score(KPS) ≥ 70, focal tumor, and lack of uncontrollable epilepsy or significant co-morbidity. The study is designed to detect a 20% increase in the overall survival rate 12 months(OS12) assuming OS12=40% in the control group and OS12= 60% in the intervention group. Secondary endpoints include hazard ratio of overall survival and progression-free survival, objective response rate, QoL, KPS, steroid dose, and toxicity. Patients will be followed for the whole trial period(36 months). The average expected follow-up is 18 months and includes regular assessment of toxicity, response and QoL. Endpoint data will be collected at the end of the trial, occurrence of suspected unexpected serious adverse reactions(SUSARs) or unacceptable serious adverse events(SAEs), withdrawal of consent, or loss-to-follow-up.
MBCL-46. TREATMENT OF RECURRENT WINGLESS-ACTIVATED MEDULLOBLASTOMA (Wnt-MB) INCORPORATING MARROW-ABLATIVE THIOTEPA AND CARBOPLATIN CHEMOTHERAPY (HDCx) AND AUTOLOGOUS HEMATOPOIETIC PROGENITOR CELL RESCUE (AuHPCR): A DUAL REPORT
Authors: Micah K Harris, Zachary N Funk, Daniel R Boué, Christopher R Pierson, Jeremy Jones, Jeffrey Leonard, Rolla Abu-Arja, Jeffrey Auletta, Diana S Osorio, Margaret Shatara, Stephan R Paul, Jonathan L Finlay, Mohamed S AbdelBaki
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Wnt-MB infers an excellent prognosis, and metastatic disease is rare. However, specific treatment strategies and patterns of failure for patients with recurrent Wnt-MB are unknown. We report two cases of recurrent beta-catenin nucleopositive Wnt-MBs treated with an irradiation-sparing strategy, incorporating HDCx/AuHPCR. PATIENT 1: A nine-year-old female experienced local recurrence of a non-metastatic Wnt-MB nine months after gross total resection (GTR) followed by 18Gy craniospinal irradiation (CSI) with primary site boost to 54Gy, accompanied by weekly vincristine, followed by a maintenance regimen of nine cycles of cisplatin/lomustine/vincristine alternating with cyclophosphamide/vincristine every third cycle. GTR of the relapsed tumor was followed by three cycles of HDCx/AuHPCR. She is disease-free for over three years following relapse treatment. PATIENT 2: A 17-year-old male initially underwent GTR, followed by 23.4Gy CSI with 54Gy posterior fossa boost with concomitant weekly vincristine, followed by a maintenance regimen that included nine alternating cycles of vincristine/lomustine/cisplatin and cyclophosphamide/vincristine. Isolated right frontal horn metastatic recurrence developed 19 months post-treatment; three cycles of irinotecan/temozolomide/bevacizumab and gamma-knife radiosurgery produced complete response. A second isolated metastatic recurrence within the left frontal horn occurred 13 months post-treatment, which was treated with two cycles of cyclophosphamide/etoposide followed by two cycles of HDCx/AuHPCR. MRI of the brain showed no residual tumor one month post-treatment. He currently awaits follow-up stereotactic radiosurgery. CONCLUSION Patients with recurrent Wnt-MB may be treated with curative intent using a multi-disciplinary approach that includes HDCx/AuHPCR, and minimization or avoidance of re-irradiation.
Using Quality-of-Life Measures to Determine the Ideal Bariatric Procedure
Authors: Grace F. Chao, Oliver A. Varban, Amir A. Ghaferi
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery 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 Surgery journal
Peripheral T-Cell Lymphomas–Not Otherwise Specified: A Shrinking Entity?
Authors: Steven M. Horwitz
Journal: Journal of the National Comprehensive Cancer Network (2020)

Peripheral T-cell lymphomas–not otherwise specified (PTCL-NOS) is a broad category of biologically and clinically heterogeneous diseases, which likely does not have a single treatment paradigm. Understanding of subtype-specific approaches is leading to more individualized therapy. There are also therapeutic vulnerabilities to target, such as CD30, JAK/STAT pathway, and epigenetic modifiers, that may cross different histologic subtypes. As new therapies evolve, however, it is important to understand in which situations current standard treatments work, because some of these treatments, such as combination chemotherapy, are potentially curative for a subset of patients. For certain populations, adding to these chemotherapy backbones will produce the best results. For other populations, entirely new approaches may be appropriate. Future treatment advances will, in part, be made by enriching populations based on their likelihood of response to specific therapies and utilizing biomarker-driven or biomarker-informed strategies.
Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Authors: P W Horby, A Roddick, E Spata, N Staplin, Emberson, G Pessoa-Amorim, L Peto, M Campbell, C Brightling, B Prudon, D Chadwick, A Ustianowski, A Ashish, S Todd, B Yates, R Buttery, S Scott, D Maseda, J K Baillie, M H Buch, L C Chappell, J N Day, S N Faust, T Jaki, K Jeffery, E Juszczak, W S Lim, A Montgomery, A Mumford, K Rowan, G Thwaites, M Mafham, R Haynes, M J Landray
Journal: The Lancet (2020)
COVD-02. ADAPTING RNA-NANOPARTICLE VACCINES FROM GLIOBLASTOMA TO SARS-COV-2
Authors: Hector Mendez-Gomez, Paul Castillo, Noah Jones, Sadeem Qdaisat, Frances Weidert, Duane Mitchell, Elias Sayour
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Glioblastoma (GBM) can be an effective teacher in the war on COVID-19, as an operative vaccine for either must elicit near-immediate protective responses that overcomes disease heterogeneity and immune suppression. Current prophylactic strategies against COVID-19 utilize mRNA vaccines targeting small fragments of the SARS-CoV-2 genome, but these may not induce robust T cell responses or elicit immunity quickly enough. OBJECTIVE We sought to adapt an FDA-IND approved mRNA vaccine in GBM against COVID-19 for: 1) activation of near immediate immune responses, 2) targeting of full-length SARS-CoV-2 structural proteins, and 3) induction of bidirectional (B and T cell) adaptive immunity. METHODS We utilized a novel engineering design that layers mRNA into a lipid-nanoparticle (NP) shell (much like an onion); this allows greater packaging of mRNA per particle to quickly boost innate/adaptive immune responses against full-length glioblastoma antigens or SARS-CoV-2 structural proteins. RESULTS In small and large animal models, RNA-NPs safely mimic viremia activating the quiescent immune system in only a few hours for induction of protective immunity against its mRNA payload. RNA-NPs activate dendritic cells (DCs), upregulate critical innate gene signatures, and induce antigen-specific cellular and humoral immunity. We found that mice receiving SARS-CoV-2 spike RNA-NPs had more effector T cells after vaccination with significant memory recall expansion after in vitro re-stimulation with overlapping SARS-CoV-2 spike peptide mix. We also found increased release of MIP-1-alpha (i.e. CCL3) previously shown by our group (Mitchell et al. Nature 2015) to be responsible for Th1 mediated memory recall to infectious vaccine antigens in GBM patients. CONCLUSION SARS-CoV-2 RNA-NPs elicit memory recall response after vaccination. We have obtained FDA-IND approval (BB-19304, Sayour) in GBM with SARS-CoV-2 specific amendment (BB-20871) underway to support first-in-human trials of RNA-NPs targeting both GBM and COVID-19.
Stress Echocardiography: Diastole to the Rescue⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Theodore P. Abraham, Hsin-Yueh Liang
Journal: Journal of the American College of Cardiology (2009)
DIPG-38. ADDITION OF MULTIMODAL IMMUNOTHERAPY TO COMBINATION TREATMENT STRATEGIES FOR CHILDREN WITH DIPG: FINAL RESULTS OF A COHORT OF CHILDREN
Authors: Stefaan Van Gool, Jennifer Makalowski, Erin R Bonner, Oliver Feyen, Matthias Domogalla, Lothar Prix, Volker Schirrmacher, Javad Nazarian, Wilfried Stücker
Journal: Neuro-Oncology (2020)

Abstract The prognosis of children with Diffuse Intrinsic Pontine Glioma (DIPG) remains dismal in spite of radio- and chemotherapy or therapies based on molecular biology diagnostics. Immunotherapy is a powerful and promising approach for improving the overall survival (OS). A retrospective analysis for feasibility, immune responsiveness and OS was performed on 41 children treated in compassionate use with Newcastle Disease Virus, hyperthermia and autologous dendritic cell vaccines as part of an individualized combined treatment approach for DIPG patients at diagnosis (n=28), or at time of progression (n=13). All except one patient had reduced values of at least one immune test before starting immunotherapy. In all patients at least one PanTum Detect test was outside the normal range. Ten patients had PDL1 mRNA expression in circulating tumor cells at diagnosis. Multimodal immunotherapy was feasible as scheduled, until progression, in all patients without major toxicity. When immunotherapy was part of primary treatment, median PFS and OS were 8.4m and 14.4m respectively with a 2-year OS of 10.7%. When immunotherapy was given at the time of progression, median PFS and OS calculated from diagnosis were 6.5m and 9.1m respectively. Th1 shift and rise in PanTum Detect test scores were linked with longer OS. Multimodal immunotherapy is feasible without major toxicity, and its value as part of a combination treatment for primary diagnosed DIPG should be elaborated in clinical trials.