tbuckley/cabot-search huggingface dataset:
PATH-27. MGMT PROMOTER STATUS IN IDH1/2 MUTANT ANAPLASTIC ASTROCYTOMA PATIENTS ASSESSED BY DNA METHYLATION PROFILING AND QMS-PCR: A REPORT FROM THE EORTC BRAIN TUMOR GROUP
Authors: Mircea Tesileanu, Pim French, Marc Sanson, Alba Ariela Brandes, Wolfgang Wick, Paul Clement, Johan Kros, Thierry Gorlia, Vassilis Golfinopoulos, Martin van den Bent
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Temozolomide efficacy in high-grade glioma is related to MGMTp methylation. We compared the prognostic and predictive effect of MGMTp between DNA methylation profiling (MGMT-STP27 model) and qMS-PCR in IDH1/2mt anaplastic astrocytoma patients. METHODS The 2x2 factorial design phase III CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4Gy radiotherapy, radiotherapy with concurrent temozolomide, radiotherapy with 12 cycles of adjuvant temozolomide, or radiotherapy with concurrent and adjuvant temozolomide. MGMTp methylation status was assessed with the MGMT-STP27 model using 850k EPIC data, and qMS-PCR. IDH1/2 mutation status was determined with next-generation sequencing. OS was measured from randomization date. RESULTS We identified 444 IDH1/2mt anaplastic astrocytoma patients. MGMTp was methylated in 365/440 patients (83.0%) with MGMT-STP27 data, and 168/361 patients (46.5%) with qMS-PCR data. The agreement between both modalities is 59.9% (Cohen’s Kappa score 0.229). At database lock, 289 patients with MGMT-STP27 data were alive and 236 patients with qMS-PCR data. The median OS of MGMTp methylated glioma patients was 9.1 yrs [95%CI 7.5-not reached] for the MGMT-STP27 model, and not reached [95%CI 9.1-not reached] for qMS-PCR. For MGMTp unmethylated glioma patients, the median OS was 6.9 yrs [95%CI 6.2-not reached] for the MGMT-STP27 model, and 6.8 yrs [95%CI 6.2-9.7] for qMS-PCR. The HR for OS based on MGMTp methylation was 0.88 [95%CI 0.58-1.31] for the MGMT-STP27 model, and 0.72 [95%CI 0.50-1.03]) for qMS-PCR. The HR for OS after radiotherapy with any temozolomide vs radiotherapy alone for the MGMT-STP27 model was 0.53 [95%CI 0.37-0.78] for MGMTp methylated, and 0.54 [95%CI 0.25-1.18] for MGMTp unmethylated glioma patients; and for MS-PCR was 0.34 [95%CI 0.19-0.61] for MGMTp methylated, and 0.53 [95%CI 0.33-0.85] for MGMTp unmethylated glioma patients. CONCLUSION MGMTp methylation, regardless of assay, was neither prognostic nor predictive for outcome to temozolomide in IDH1/2mt anaplastic astrocytoma patients.
“Opium Antidotes,” and Their Vendors
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
7. Diabetes Technology: <i>Standards of Medical Care in Diabetes—2022</i>
Journal: Diabetes Care (2021)

The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes the ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
Engagement of the costimulatory molecule ICOS in tissues promotes establishment of CD8+ tissue-resident memory T cells
Authors: Changwei Peng, Matthew A. Huggins, Kelsey M. Wanhainen, Todd P. Knutson, Hanbin Lu, Hristo Georgiev, Kristen L. Mittelsteadt, Nicholas N. Jarjour, Haiguang Wang, Kristin A. Hogquist, Daniel J. Campbell, Henrique Borges da Silva, Stephen C. Jameson
Journal: Immunity (2021)
Molecular Response Patterns in Relapsed/Refractory AML Patients Treated with Selinexor and Chemotherapy
Authors: Piroska Klement, Walter Fiedler, Razif Gabdoulline, Louisa-Kristin Dallmann, Clara Wienecke, Johannes Schiller, Christian Kandziora, Katrin Teich, Bennet Heida, Maximilian Brandes, Carolin Funke, Martin Wichmann, Basem Othman, Jörg Chromik, Konstantin Büttner, Stefanie Amberg, Maxim Kebenko, Vera Schlipfenbacher, Anne C Wilke, Franziska Modemann, Melanie Janning, Hubert Serve, Carsten Bokemeyer, Ute Deppermann, Anne L. Kranich, Arnold Ganser, Felicitas Thol, Michael Heuser
Journal: Blood (2021)
Abstract 10169: Changes in Cytokine Responses by Treatment with Tocilizumab After Out-of-Hospital Cardiac Arrest - A Sub Study of the IMICA Trial
Authors: Martin A Meyer, Mette Bjerre, Sebastian Wiberg, Johannes Grand, Anna Sina P Meyer, Laust E Obling, Jesper Kjaergaard, Christian Hassager
Journal: Circulation (2021)

Background: Out-of-hospital cardiac arrest (OHCA) patients are at high risk of morbidity and mortality attributable to the post-cardiac arrest syndrome, in which systemic inflammation is a major component. Cytokines are involved in many processes, including inflammation. In the IMICA trial, treatment with the interleukin 6 receptor (IL-6R) antagonist tocilizumab in resuscitated comatose OHCA patients reduced systemic inflammation as characterized by a greatly reduced CRP response and lower levels of leukocytes as compared to placebo. Markers of myocardial injury were also reduced by treatment. Aim: To investigate changes in cytokine levels induced by blocking the IL-6-mediated signaling with tocilizumab after OHCA by employing a broad cytokine panel. Methods: We randomized 80 patients to a single infusion of tocilizumab 8 mg/kg or placebo after admission. Blood samples were drawn at 0, 24, 48, and 72 hours. Cytokines were measured using a 17-plex cytokine assay: G-CSF, GM-CSF, IFN-γ, MCP-1, MIP-1β, TNF-α, IL- 1β, 2, 4-8, 10, 12, 13, and 17. Data were log2 transformed and analyzed by constrained linear mixed models. Results: Most cytokines had temporal changes after OHCA. However, only for IL- 5, 6 (Figure) and 17 were the treatment-by-time interactions significant, all p&lt;0.05. Circulating IL-5 and in particular IL-6 was markedly increased by inhibition of the IL-6R with tocilizumab as compared to the placebo group. For IL-17 the changes were less pronounced and only differed between groups at 72 hours. Conclusions: Treatment with the IL-6R antagonist, tocilizumab, did not alter the cytokine responses in general, however, IL-5 and IL-6 were markedly increased. Experimental data suggests that IL-5 may play a role in cardiac recovery after ischemia. Blockage of the IL-6R greatly increased the IL-6 levels, and as the CRP response was greatly reduced by tocilizumab, a response strongly associated with IL-6, it can be demonstrated that the function of IL-6 was blunted.
Prospective Paired Comparison of 123I-FP-CIT SPECT Images Obtained With a 360°-CZT and a Conventional Camera
Authors: Yuliya Piatkova, Pierre Payoux, Caroline Boursier, Manon Bordonne, Veronique Roch, Pierre-Yves Marie, Gabriela Hossu, Laëtitia Imbert, Antoine Verger
Journal: Clinical Nuclear Medicine (2021)

This study aimed to compare 123I-FP-CIT SPECT imaging obtained from a 360° cadmium-zinc-telluride (CZT) camera with different focus configurations and from a conventional Anger camera.This prospective study (NCT03980418) included patients referred to 123I-FP-CIT SPECT imaging who consecutively underwent a 30-minute acquisition on a conventional camera immediately followed by two 15-minute acquisitions on the 360°-CZT camera with, respectively, striatum and brain focus and reconstruction parameters to give equivalent contrast ratios, albeit with higher spatial resolution for the CZT camera. Tomographic count sensitivities were calculated. The images were analyzed through visual, according to 5 independent physicians, and automatic semiquantitative analyses.Ninety-two patients were included in this study. The 360°-CZT camera tomographic count sensitivities showed increases of +25% and +18% for striatum and brain focus, respectively, as well as significantly higher quality scores (P ≤ 0.04) in comparison to the conventional camera. The κ scores of consensual visual analysis were 0.80 and 0.85, and correlation coefficients of semiquantitative analysis for striatum uptakes were 0.75 and 0.76 for the comparisons of images obtained with the 2 cameras, with striatum and brain focus, respectively, for the CZT camera. Advanced age was the single predictor of discordant cases (10/92 [11%]) showing systematically abnormal scans with the conventional camera, potentially as a result of partial volume effect.Irrespective of focus mode, this high-sensitivity 360°-CZT camera provides concordant 123I-FP-CIT SPECT results when compared with a conventional camera, but with shorter acquisition times, higher image quality, and few discordant cases possibly explained by its higher spatial resolution.
Single-cell profiling of immune system alterations in lymphoid, barrier and solid tissues in aged mice
Authors: Sinduya Krishnarajah, Florian Ingelfinger, Ekaterina Friebel, Dilay Cansever, Ana Amorim, Myrto Andreadou, David Bamert, Gioana Litscher, Mirjam Lutz, Maud Mayoux, Sarah Mundt, Frederike Ridder, Colin Sparano, Sebastian Anton Stifter, Can Ulutekin, Susanne Unger, Marijne Vermeer, Pascale Zwicky, Melanie Greter, Sonia Tugues, Donatella De Feo, Burkhard Becher
Journal: Nature Aging (2021)
Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial
Authors: Daniel J. DeAngelo, Deepti H. Radia, Tracy I. George, William A. Robinson, Albert T. Quiery, Mark W. Drummond, Prithviraj Bose, Elizabeth O. Hexner, Elliott F. Winton, Hans-Peter Horny, Meera Tugnait, Oleg Schmidt-Kittler, Erica K. Evans, Hui-Min Lin, Brenton G. Mar, Srdan Verstovsek, Michael W. Deininger, Jason Gotlib
Journal: Nature Medicine (2021)

Abstract Advanced systemic mastocytosis (AdvSM) is a rare hematologic neoplasm driven by the KIT D816V mutation and associated with poor survival. This phase 1 study ( NCT02561988 ) evaluated avapritinib (BLU-285), a selective KIT D816V inhibitor, in patients with AdvSM. The primary endpoints were the maximum tolerated dose, recommended phase 2 dose and safety of avapritinib. Secondary endpoints included overall response rate and changes in measures of mast cell burden. Avapritinib was evaluated at doses of 30–400 mg once daily in 86 patients, 69 with centrally confirmed AdvSM. Maximum tolerated dose was not reached, and 200 mg and 300 mg daily were studied in dose-expansion cohorts. The most frequent adverse events observed were periorbital edema (69%), anemia (55%), diarrhea (45%), thrombocytopenia (44%) and nausea (44%). Intracranial bleeding occurred in 13% overall, but in only 1% of patients without severe thrombocytopenia (platelets &lt;50 × 10 9 /l). In 53 response-evaluable patients, the overall response rate was 75%. The complete remission rate was 36%. Avapritinib elicited ≥50% reductions in marrow mast cells and serum tryptase in 92% and 99% of patients, respectively. Avapritinib induced deep and durable responses, including molecular remission of KIT D816V in patients with AdvSM, and was well tolerated at the recommended phase 2 dose of 200 mg daily.
Brentuximab – effective for mycosis fungoides and Sézary syndrome
Journal: British Journal of Dermatology (2021)

Mycosis fungoides (MF) and Sézary syndrome (SS) are rare forms of skin cancer (T‐cell lymphoma) arising in the skin from white blood cells. They are variable in their behaviour and difficult to treat. Brentuximab vedotin (BV) is a drug that targets CD30, a protein found on the surface of activated T lymphocytes. CD30 is often expressed in patients with MF and SS.
Abstract 9499: Prehospital Factors Associated With Cardiopulmonary Resuscitation Performance in Out-of-Hospital Cardiac Arrests
Authors: Melanie Villani, Ziad Nehme, Emily Andrew, Jocasta Ball, Karen Smith
Journal: Circulation (2021)

Introduction: Although high quality cardiopulmonary resuscitation (CPR) has been associated with improvements in survival from cardiac arrest, little is known about the arrest factors that influence CPR performance. This study examined the association between CPR performance and patient and arrest factors in out-of-hospital cardiac arrest (OHCA). Methods: A retrospective observational study using data from a statewide cardiac arrest registry in Victoria, Australia. The study included 2,408 adult, medical OHCA patients who arrested between 11 February 2019 and 10 February 2021. Fractional and logistic regression models were used to analyse factors associated with CPR performance outcomes, including the proportion of compressions at target depth and target rate and a compression fraction ≥90%. Results: The median proportion of compressions at target depth and target rate were 80% (interquartile range [IQR] 58, 92.5) and 62% (IQR 40, 79), respectively, and 70% achieved a compression fraction ≥90%. After multivariable adjustment, achieving a compression depth in the target range was associated with female sex (OR 1.14 [95% CI: 1.02, 1.28]), patient weight (per 10 kg increase, OR 1.08 [95% CI: 1.05, 1.12]), aged care facility location (OR 0.74 [95% CI: 0.58, 0.94]), fire-fighter presence (OR 1.29 [95% CI: 1.14, 1.46]), resuscitation duration (per 5 min increase, OR 1.08 [95% CI: 1.06, 1.10]) and number of rescuers (per 1 person increase, OR 1.06 [95% CI: 1.03, 1.09]). Achieving compressions within target rate were associated with public location (OR 0.81 [95% CI: 0.72, 0.91]) and fire-fighter presence (OR 1.12 [95% CI: 1.02, 1.24]). Achieving a compression fraction ≥90% was associated with female sex (OR 0.75 [95% CI: 0.62, 0.91]), arrests witnessed by emergency services (OR 0.44 [95% CI: 0.32, 0.61]), initial shockable rhythms (OR 0.66 [95% CI: 0.53, 0.81]), fire-fighter presence (OR 1.24 [95% CI: 1.01, 1.54]) and resuscitation duration (per 5 min increase, OR 1.05 [95% CI: 1.02, 1.08]). Conclusion: This study demonstrates that several prehospital factors that are associated with CPR performance which may help inform operational strategies to improve OHCA outcomes.
Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial
Authors: Lars Erik Kristensen, Mauro Keiserman, Kim Papp, Leslie McCasland, Douglas White, Wenjing Lu, Zailong Wang, Ahmed M Soliman, Ann Eldred, Lisa Barcomb, Frank Behrens
Journal: Annals of the Rheumatic Diseases (2021)

Objective To evaluate risankizumab, a biological therapy that inhibits interleukin 23, in patients with active psoriatic arthritis (PsA) who have responded inadequately or are intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD). Methods In the randomised, placebo-controlled, double-blind KEEPsAKE 1 trial, 964 patients with active PsA were randomised (1:1) to receive risankizumab 150 mg or placebo at weeks 0, 4 and 16. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Here, we report the results from the 24-week double-blind period; the open-label period with all patients receiving risankizumab is ongoing. Results At week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (57.3% vs placebo, 33.5%; p&lt;0.001). Significant differences were also observed for risankizumab versus placebo for the first eight ranked secondary endpoints, including skin and nail psoriasis endpoints, minimal disease activity and resolution of enthesitis and dactylitis (p&lt;0.001). Adverse events and serious adverse events were reported at similar rates in the risankizumab and placebo groups. Serious infections were reported for 1.0% and 1.2% of patients receiving risankizumab and placebo, respectively. There was one death in the risankizumab group (urosepsis deemed unrelated to the study drug). Conclusions Risankizumab treatment results in significantly greater improvement of signs and symptoms of PsA compared with placebo and is well tolerated in patients with active PsA who have responded inadequately or are intolerant to ≥1 csDMARD. Trial registration number NCT03675308 .
Redefining nonmeasurable multiple myeloma using mass spectrometry
Authors: Hannah V. Giles, Mark A. Cook, Mark Trehane Drayson, Gordon Cook, Nicola Jane Wright, Simon John North, Stephen Harding, David A. Cairns, Anna Hockaday, Martin F. Kaiser, Paul Moss, Faith E. Davies, Gareth J. Morgan, Graham Jackson, Guy Pratt
Journal: Blood (2021)
The importance of rigorous methods in observational comparative effectiveness studies of rare diseases: comment on the article by Ruperto et al
Authors: Yukiko Kimura, Mei‐Sing Ong, George Tomlinson, Sarah Ringold, Laura E. Schanberg, Brian M. Feldman, Anne Dennos, Vincent Del Gaizo, Katherine L. Murphy, Marc Natter
Journal: Arthritis & Rheumatology (2021)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Abstract 10336: ECPR <sup>2</sup> : Expert Consensus on PeRcutaneous Cannulation for Extracorporeal CardioPulmonary Resuscitation
Authors: Florian F Schmitzberger, Nathan L Haas, Ryan A Coute, Jason Bartos, Amy E Hackmann, Jonathan Haft, Cindy H Hsu, Alice Hutin, Lionel Lamhaut, Jonathan Marinaro, Ken Nagao, Takahiro Nakashima, Robert W Neumar, Zack M Shinar, Sage Whitmore, Demetris Yannopoulos, William Peterson
Journal: Circulation (2021)

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a promising resuscitation strategy for select patients suffering out-of-hospital cardiac arrest (OHCA), though limited data exists regarding detailed best practices for the complex process of initiating ECPR following OHCA. Hypothesis: Expert consensus using a modified Delphi process can systematically identify detailed best practices for ECPR initiation following adult non-traumatic OHCA. Methods: We utilized a modified Delphi process consisting of two survey rounds and a virtual consensus meeting to systematically identify best practices for ECPR initiation following adult non-traumatic OHCA. A modified Delphi process builds content validity and is an accepted method to develop consensus by eliciting expert opinions through multiple rounds of questionnaires. Consensus was achieved when items reached a high level of agreement, defined as greater than 80% responses for a particular item rated a 4 or 5 on a 5-point Likert scale. Results: Snowball sampling generated a panel of 14 content experts, composed of physicians from four continents and four primary specialties. Seven existing institutional protocols for ECPR cannulation following OHCA were identified and merged into a single comprehensive list of 216 items. The panel ultimately reached consensus on 95 items: Prior to Patient Arrival (8 items), Inclusion Criteria (8), Exclusion Criteria (7), Patient Arrival (8), ECPR Cannulation (21), Go On Pump (17), and Post-Cannulation (26). Conclusion: We present a list of essential items for initiation of ECPR following adult non-traumatic OHCA, generated using a modified Delphi process from an international panel of content experts. These findings can benefit centers currently performing ECPR for OHCA in quality assurance and performance improvement, and can serve as a template for new ECPR programs to follow.
Abstract 17233: Primary Intimal Sarcoma Of The Pulmonary Artery In A Patient With Laboratory Confirmed Heterozygous Factor V Leiden Mutation: A Case Report
Authors: Mark Pintea, Melody Hermel, Sandeep Mehta, Curtiss Stinis, Rajeev Mohan, Ajay Srivastava
Journal: Circulation (2021)

Pulmonary artery intimal sarcoma (PAIS) is a rare tumor associated with progressively increasing dyspnea, atypical chest pain, and pulmonary hypertension. Owing to overlap in presentation, PAIS can be misdiagnosed as pulmonary thromboembolism (PTE). Here we present the case of a 59-year-old male with heterozygous Factor V Leiden mutation, history of deep vein thrombosis (DVT), and recent PTE presenting to urgent care with cough, mild orthopnea, and exertional dyspnea. Transthoracic echocardiogram (TTE) revealed severely dilated right ventricle with moderately decreased function and severe pulmonary hypertension with pulmonary arterial (PA) pressure of 93mmHg. Computed tomography angiography of the chest revealed massive central PTE. Given hemodynamic stability, saturating well on room air and simplified PESI score of 0, Pulmonology recommended discharge with anticoagulation. The patient returned a month later with three weeks of increased dyspnea on exertion, worsened right ventricular function as well as possible new mobile thrombus extending into the right ventricular outflow tract (RVOT). Due to presumed failure of medical therapy, Cardiology placed the patient on venoarterial extracorporeal membrane oxygenation (VA-ECMO) followed by attempted mechanical thrombectomy using both the Angiovac and Penumbra CAT12 systems. Both systems failed to remove substantial material from the PA. The next day, TTE revealed increased PA pressure of 132mmHg.The patient underwent emergent bilateral thromboendarterectomy with a mass discovered involving the pulmonary valve (PV), RVOT, both left and right PAs, along with invasion into the PA wall. The mass was resected, the PV valve replaced, the main PA and left PA reconstructed, and pericardial patch reconstruction of the RVOT was performed. The mass was determined to be a PAIS of French Federation of Comprehensive Cancer Centres (FNCLCC) Grade 3. Two months after uncomplicated recovery, chemotherapy was initiated. Securing the diagnosis of PAIS is challenging. However, collaboration between clinicians, radiologists, and pathologists increases the likelihood of recognizing subtle markers that can differentiate PAIS from illnesses with a similar presentation.