tbuckley/cabot-search huggingface dataset:
Bortezomib, lenalidomide, and dexamethasone (VRd) ± daratumumab (DARA) in patients (pts) with transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): A multicenter, randomized, phase III study (PERSEUS).
Authors: Pieter Sonneveld, Annemiek Broijl, Francesca Gay, Mario Boccadoro, Hermann Einsele, Joan Blade, Meletios A. Dimopoulos, Michel Delforge, Andrew Spencer, Roman Hajek, Fredrik Schjesvold, Sarah Lonergan, Elena Smith, Robin L. Carson, Wendy Crist, Wendy S. Garvin, Jessica Vermeulen, Philippe Moreau
Journal: Journal of Clinical Oncology (2019)

TPS8055 Background: DARA, a human, CD38-targeting, IgGκ monoclonal antibody, is approved in many countries for use as monotherapy in relapsed/refractory MM (RRMM), and in combination with standard-of-care regimens in RRMM and transplant-ineligible NDMM. Given the initial safety and efficacy observed with DARA plus VRd (D-VRd) in the safety run-in cohort of the ongoing phase 2 GRIFFIN study in TE NDMM pts, the phase 3 PERSEUS study will evaluate the efficacy and safety of D-VRd versus VRd alone in TE NDMM. Methods: This is an ongoing multicenter, open-label, randomized phase 3 study of D-VRd versus VRd alone in TE NDMM pts. Approximately 690 pts across Europe will be stratified by ISS stage and cytogenetic risk (high risk defined as presence of del17p, t[4;14], or t[14;16]) and randomized in a 1:1 ratio. All pts will receive VRd (V: 1.3 mg/m 2 SC Days 1, 4, 8, 11; R: 25 mg PO Days 1-21; d: 40 mg PO Days 1-4, 9-12) for 4 pre-transplant induction and 2 post-transplant consolidation cycles (all 28-d cycles), followed by R (10 mg PO Days 1-28) maintenance until progressive disease (PD). Pts in the DARA group will also receive subcutaneous DARA (1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; Halozyme]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W in maintenance Cycles 7+ until PD. After induction, pts will undergo melphalan 200 mg/m 2 conditioning and autologous stem cell transplantation (ASCT). Pts in the DARA group who achieve sustained minimal residual disease (MRD) negativity (10 –5 threshold; assessed by NGS) for 12 months after ≥24 months of maintenance will stop DARA but continue R maintenance until PD; upon loss of CR or MRD-negative status, pts will restart DARA treatment. All pts will receive preinfusion medications. The primary endpoint is progression-free survival (PFS). Secondary endpoints include MRD-negative rate, overall response rate, PFS on next line of therapy, overall survival, time to and duration of response, health-related quality of life, pharmacokinetics, immunogenicity, stem cell yield after mobilization, time to engraftment post-ASCT, and safety. Clinical trial information: NCT03710603.
Prognostic Value of Pretreatment Radiomic Features of 18F-FDG PET in Patients With Hodgkin Lymphoma
Authors: Kun-Han Lue, Yi-Feng Wu, Shu-Hsin Liu, Tsung-Cheng Hsieh, Keh-Shih Chuang, Hsin-Hon Lin, Yu-Hung Chen
Journal: Clinical Nuclear Medicine (2019)

This study investigated whether a radiomic analysis of pretreatment F-FDG PET can predict prognosis in patients with Hodgkin lymphoma (HL).Forty-two patients who were diagnosed as having HL and underwent pretreatment F-FDG PET scans were retrospectively enrolled. For each patient, we extracted 450 radiomic features from PET images. The prognostic significance of the clinical and radiomic features was assessed in relation to progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic curve, Cox proportional hazards regression, and Kaplan-Meier analyses were performed to examine the potential independent predictors and to evaluate the predictive value.Intensity nonuniformity extracted from a gray-level run-length matrix and the Ann Arbor stage were independently associated with PFS (hazard ratio [HR] = 22.8, P < 0.001; HR = 7.6, P = 0.024) and OS (HR = 14.5, P = 0.012; HR = 8.5, P = 0.048), respectively. In addition, SUV kurtosis was an independent prognosticator for PFS (HR = 6.6, P = 0.026). We devised a prognostic scoring system based on these 3 risk predictors. The proposed scoring system further improved the risk stratification of the current staging classification (P < 0.001).The radiomic feature intensity nonuniformity is an independent prognostic predictor of PFS and OS in patients with HL. We devised a prognostic scoring system, which may be more beneficial for patient risk stratification in guiding therapy compared with the current Ann Arbor staging system.
PD-1 blockade after PD-(L)1 inhibitors in head and neck cancer: Role of immunotherapy rechallenge.
Authors: Santiago Cabezas-Camarero, Pedro Pérez-Segura
Journal: Journal of Clinical Oncology (2019)

69 Background: Immunotherapy (IO) has shown to improve survival in recurrent or metastatic (R/M) squamous cell cancer of the head and neck (SCCHN) with a better toxicity profile than chemotherapy (CT). An increased objective response rate (ORR) to CT has been shown after PD(L)1 blockade in SCCHN and other solid tumors. However, there are no data regarding the safety and efficacy of PD(L)1 rechallenge in SCCHN. Methods: Retrospective study of patients with R/M SCCHN treated with PD-1 inhibitors after an overt clinical and radiological progression to PD(L)1 blockade. Post-IO CT regimens, overall survival (OS), objective response rates (ORR) and percentage of tumor reduction (PTR) with post-IO CT and toxicity of IO rechallenge were recorded. Results: Eight patients treated between October 2016 and October 2018, were included. All patients received the first IO (1 st -IO) treatment within clinical trials (anti-PDL1: 7; anti-PD1: 1), and received rescue cetuximab-based CT at progression (PD) (ERBITAX: 7; EXTREME: 1). ORR to post-IO 1 st rescue CT (1RCT): 7 partial responses (PR), 1 stable disease (SD). PTR to 1RCT (median): 45% (range: 40-80). All second IO (2 nd -IO) treatments consisted of PD1 inhibitors (nivolumab) and 6 received rescue CT (2RCT) at PD (ERBITAX: 1; wkCDDP-Cetuximab: 2; EXTREME: 3). Only 1of 6 evaluable patients responded to 2 nd -IO with 5 PD as best response. Median duration of 2 nd -IO: 3 months (range: 1-6). ORR to 2RCT (5 evaluable): 4 PR, 1 PD. PTR to 2RCT (median): 30% (range: 30-80). No G3/4 toxicities were detected during 2 nd -IO. Conclusions: No new safety signals were encountered during PD-1 blockade in patients with SCCHN previously treated with PD-(L)1 inhibitors. First and second IO treatments associated with increased response rates to subsequent CT compared with historical data. Clinical trials should try to address the optimal treatment sequence in the IO era.
Erratum: Corrigendum: RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci
Authors: Susannah L Hewitt, Bu Yin, Yanhong Ji, Julie Chaumeil, Katarzyna Marszalek, Jeannette Tenthorey, Giorgia Salvagiotto, Natalie Steinel, Laura B Ramsey, Jacques Ghysdael, Michael A Farrar, Barry P Sleckman, David G Schatz, Meinrad Busslinger, Craig H Bassing, Jane A Skok
Journal: Nature Immunology (2010)
Preferential enrichment of myeloid-derived suppressor cell subsets in patients with metastatic melanoma.
Authors: Christiane Meyer, Laurene Cagnon, Nicole Montandon, Grégoire Berthod, Loredana Leyvraz, Olivier Michielin, Emanuela Romano, Daniel E Speiser
Journal: Journal of Clinical Oncology (2012)

e19050 Background: Myeloid derived suppressor cells (MDSC) are key immunosuppressive cells enriched in peripheral blood during chronic inflammation. While these cells have been extensively studied in mice, their human counterparts are less well characterized. Several MDSC populations have been identified in cancer patients, depending on tumor type and experimental settings. MDSC include immature macrophages, granulocytes and dendritic cells, at different degree of maturation, from immature CD33 + , to mature CD14 + and CD15 + HLA-DR - cells. The goal of this study was to characterize myeloid cells in melanoma patients compared with healthy donors (HD) to identify inflammation-mediated alterations involved in melanoma progression. Methods: PBMC were isolated by Lymphoprep gradient centrifugation from fresh blood samples of patients with malignant melanoma. We performed 9-color FACS staining of the freshly isolated cells. Results: CD15 + granulocytic MDSC are enriched in the mononuclear cell layer after gradient centrifugation, together with the CD14 + monocytic MDSCs. They display significantly different sedimentation abilities compared with neutrophils. Furthermore, CD14 and CD15 were partially co-expressed by the monocytic and granulocytic MDSC subsets, respectively. Our data show that CD14 + HLA-DR - monocytic and CD15 + HLA-DR - granulocytic MDSC were significantly enriched in peripheral blood of metastatic melanoma patients, regardless of whether or not they received any prior therapy for metastatic melanoma. The more immature CD33 + CD11b - subset was found at significantly lower frequencies in melanoma patients compared with HD. We found a trend for accumulation of non-classical CD14 + CD16 + monocytes. However, the increased percentages did not differ significantly from HD. The frequencies of classical CD14 + CD16 - monocytes were unchanged. Conclusions: Melanoma is associated with increased frequencies of CD14 + monocytic and CD15 + granulocytic MDSC, and decreased frequencies of the more immature CD33 + CD11b - cells. This finding demonstrates tumor-mediated changes in the composition of myeloid cells, which could influence response to treatment and clinical behavior of the disease.
Role of Rotavirus Vaccination in Decline in Incidence of Type 1 Diabetes—Reply
Authors: Kirsten P. Perrett, Kim Jachno, Terry M. Nolan
Journal: JAMA Pediatrics (2019)

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
Novel radioligands for imaging sigma-1 receptor in brain using positron emission tomography (PET)
Authors: Yu Lan, Ping Bai, Zude Chen, Ramesh Neelamegam, Michael S. Placzek, Hao Wang, Stephanie A. Fiedler, Jing Yang, Gengyang Yuan, Xiying Qu, Hayden R. Schmidt, Jinchun Song, Marc D. Normandin, Chongzhao Ran, Changning Wang
Journal: Acta Pharmaceutica Sinica B (2019)

The sigma-1 receptor (σ1R) is a unique intracellular protein. σ1R plays a major role in various pathological conditions in the central nervous system (CNS), implicated in several neuropsychiatric disorders. Imaging of σ1R in the brain using positron emission tomography (PET) could serve as a noninvasively tool for enhancing the understanding of the disease's pathophysiology. Moreover, σ1R PET tracers can be used for target validation and quantification in diagnosis. Herein, we describe the radiosynthesis, in vivo PET/CT imaging of novel σ1R 11C-labeled radioligands based on 6-hydroxypyridazinone, [11C]HCC0923 and [11C]HCC0929. Two radioligands have high affinities to σ1R, with good selectivity. In mice PET/CT imaging, both radioligands showed appropriate kinetics and distributions. Additionally, the specific interactions of two radioligands were reduced by compounds 13 and 15 (self-blocking). Of the two, [11C]HCC0929 was further investigated in positive ligands blocking studies, using classic σ1R agonist SA 4503 and σ1R antagonist PD 144418. Both σ1R ligands could extensively decreased the uptake of [11C]HCC0929 in mice brain. Besides, the biodistribution of major brain regions and organs of mice were determined in vivo. These studies demonstrated that two radioligands, especially [11C]HCC0929, possessed ideal imaging properties and might be valuable tools for non-invasive quantification of σ1R in brain.
Ketamine could be first of new generation of rapid acting antidepressants, say experts
Authors: Ingrid Torjesen
Journal: BMJ (2019)

Ketamine is the first truly new pharmacological approach to treating depression in the past 50 years and could herald a new generation of rapid acting antidepressants, researchers have predicted.

“We haven’t had anything really new for about 50 or 60 years,” said Allan Young, professor of mood disorders at the Institute of Psychiatry, Psychology and Neuroscience at King’s College, London, at a briefing on 12 July at London’s Science Media Centre.

Most of the new launches have been “tinkering with drugs which were really discovered in the ’50s and ’60s,” he explained. “Even the famous Prozac, which came in in the late ’80s, is really just a refinement of the tricyclic antidepressants that came in the ’50s. People say we are still in the age of steam, and we need to go to the next technological advance.”

In the past few years the focus has fallen on ketamine, …
Resuscitation Strategies Using Peripheral Perfusion vs Serum Lactate Levels
Authors: Ahmad Sabry Saleh
Journal: JAMA (2019)

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
Big rise in number of consultants is expected by 2020
Authors: Helen Jaques
Journal: BMJ (2011)

If all junior doctors who are currently training in medical specialties achieve their certificate of completion of training (CCT) and secure a consultant job, the total number of consultants will rise by 70% by 2020. Data from the Centre for Workforce Intelligence, presented at the NHS Employers conference in Liverpool this week, indicate that such an increase will cost the NHS £2.5bn.

Even if 17.5% of the current trainees shift into general practice, as recommended by the …
Catheter ablation improved quality of life more than drug therapy at 1 y in symptomatic atrial fibrillation
Authors: Gaetano Santulli
Journal: Annals of Internal Medicine (2019)

Source Citation Mark DB, Anstrom KJ, Sheng S, et al; CABANA Investigators. Effect of catheter ablation vs medical therapy on quality of life among patients with atrial fibrillation: the CABANA randomized clinical trial. JAMA. 2019. [Epub ahead of print]. 30874716
Abstract 11678: National Trends in Hospitalization of Patients With Diastolic Heart Failure and Concurrent Amyloidosis
Authors: Avirup Guha, Xiao Xiang, Devin Haddad, Benjamin Buck, Ziyan Yuan, Xu Gao, Ellen Liu, Michael Dunleavy, Mohamed Derbala, Yvonne Efebera, Ragavendra Baliga, Sakima Smith
Journal: Circulation (2017)

Introduction: Amyloidosis is a systemic disease with a high incidence of concurrent diastolic heart failure (DHF)/preserved ventricular function. Trends in hospitalization for patients with a diagn...
Clinical prognostic factors in pediatric Ewing sarcoma.
Authors: Bilal Abou Ali, Ralph Nader, Samar Muwakkit, Miguel Abboud, Hassan M.B. El Solh, Raya Hamad Saab
Journal: Journal of Clinical Oncology (2013)

10052 Background: Treatment of Ewing sarcoma necessitates coordinated multi-disciplinary care that includes chemotherapy, surgery, and/or radiation. In developed countries, patients with localized disease have an overall survival of 70-80%, compared to 20-30% for those with metastases. The outcome of children with Ewing sarcoma in less developed countries has not been adequately described. We analyzed prognostic factors for Ewing sarcoma patients treated at a single institution in Lebanon, a developing country with available multidisciplinary treatment modalities. Methods: We reviewed characteristics and outcome of 42 pediatric patients treated at a multidisciplinary cancer center in Lebanon, between January 1999 and October 2012. Kaplan Meier curves were generated to estimate survival. Results: Median age at presentation was 10 years (range 1-18), and median follow-up was 41 months (range 8-110). Commonly affected primary sites included the extremity (36%, n=15), chest wall (19%, n=8), and pelvis (14%, n=6). Tumor size was ≥ 8cm in twenty (47.6%) patients. Thirty-two patients (76%) had localized disease, and ten (24%) had metastatic disease. All patients received 14 cycles of chemotherapy, with VDC alternating with IE. Local control was surgery alone (29%, n=12), radiotherapy alone (33%, n=14), or combination (38%, n=16). For patients with localized disease, the 5-year OS and DFS rates were 68% and 55% respectively, while for metastatic disease they were 28% and 25%. Tumor recurrence was local in 8 patients, distant in 8, and combined in 2. Factors associated with improved outcome included localized disease, extremity site, surgery, and timely local control. In multivariate analysis, timing of local control and metastatic disease were prognostically significant determinants of outcome. Conclusions: Treatment of childhood Ewing sarcoma in a multidisciplinary cancer center in Lebanon results in similar survival to that in developed countries when similar protocols are applied. Strong prognostic factors included stage (localized vs. metastatic), and timing of local control. Patients who had a local control time delay of more than 3 weeks fared worse, strongly suggesting that delays in local control should be actively minimized in Ewing sarcoma.
Quantitative test of mutant EGFR and its effect on efficacy of EGFR TKI in advanced NSCLC.
Authors: Caicun Zhou, Xuefei Li, Shengxiang Ren, Guohua Yang, Wei He
Journal: Journal of Clinical Oncology (2013)

e22186 Background: It is reported that abundance of EGFR mutation is related with efficacy of EGFR TKI in advanced NSCLC patients with positive EGFR mutations. This study was designed to investigate influence of EGFR mutations and their abundance on efficacy of EGFR TKI. Methods: 141 advanced NSCLC treated with EGFR TKI and available tissue for EGFR mutations were enrolled into the study. EGFR mutation was detected with the kit of AmoyDx ARMS and concentration of mutant EGFR was detected with the method of a quantitative competitive allele specific Taqman PCR technology (qCAST). In this assay, copies from EGFR mutants were calibrated by standard curve respectively, and the mutation rates were estimated through normalizing by copies of a conserved sequence in EGFR exon2. The relationship between abundance of EGFR mutations and efficacy of EGFR TKI was analyzed. Results: The median age of patients was 59 years old, and in which 54.3% were male, 71.7% ex-somkers. Among all of the patients, adenocarcinoma accounted for 57.7%, squamous cell carcinoma 27.2%, adeno-squamous cell carcinoma 7.6%, and others 7.6%. 46.7% of patients harbored EGFR mutations, and in which 48.7% existed more than 20% abundance of EGFR mutations. Overall response rate was 31.4% and progression free survival was 5.0 months. The final analysis data will be reported at the conference. Conclusions: The abundance of EGFR mutations might affect the efficacy of EGFR-TKI, and quantitation of mutant EGFR may better predict for efficacy of EGFR TKI in advanced NSCLC.
Positive Treatment Expectancies Reduce Clinical Pain and Perceived Limitations in Movement Ability Despite Increased Experimental Pain: A Randomized Controlled Trial on Sham Opioid Infusion in Patients with Chronic Back Pain
Authors: Julia Schmitz, Maike Müller, Jan Stork, Iris Eichler, Christian Zöllner, Herta Flor, Regine Klinger
Journal: Psychotherapy and Psychosomatics (2019)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Increasing evidence for the efficacy of analgesic placebo effects in laboratory studies with healthy persons raises the question whether placebos could be used to improve the treatment of pain patients. Expectancies play a central role in shaping analgesic placebo but also nocebo effects. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; We investigated to what extent a sham opioid infusion (saline solution) produces sustained clinically relevant placebo and nocebo effects in chronic back pain patients. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Fifty-nine patients received the sham opioid infusion applied via a large drain dressing and were compared to 14 control patients without intervention (natural history, NH) while experimental pain stimuli were applied. All subjects were told that the infusion would decrease pain although in rare cases pain increase would be possible (induction of expectancy). In addition, conditioning was introduced where the participants either experienced a decrease in experimental pain (&lt;i&gt;n&lt;/i&gt; = 17; placebo conditioning), an increase (&lt;i&gt;n&lt;/i&gt; = 21; nocebo conditioning), or no change (&lt;i&gt;n&lt;/i&gt; = 21, no conditioning). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Compared to the NH group, all infusion groups showed positive treatment expectancies and significantly (&lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001) reduced clinical back pain (primary outcome) and pain-related disability (secondary outcome, assessed by self-reported functional capacity and perceived impairment of mobility). Even the nocebo conditioned group experiencing increased experimental pain developed positive treatment expectancies followed by reduced pain experience. Positive treatment expectancies and relief in clinical back pain were significantly positively correlated (&lt;i&gt;r&lt;/i&gt; = 0.72, &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.01). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; These findings suggest that it may be beneficial to explicitly shape and integrate treatment expectancies into clinical pain management.