tbuckley/cabot-search huggingface dataset:
AXL targeting restores PD-1 blockade sensitivity of STK11/LKB1 mutant NSCLC through expansion of TCF1+ CD8 T cells
Authors: Huiyu Li, Zhida Liu, Longchao Liu, Hongyi Zhang, Chuanhui Han, Luc Girard, Hyunsil Park, Anli Zhang, Chunbo Dong, Jianfeng Ye, Austin Rayford, Michael Peyton, Xiaoguang Li, Kimberley Avila, Xuezhi Cao, Shuiqing Hu, Md Maksudul Alam, Esra A. Akbay, Luisa M. Solis, Carmen Behrens, Sharia Hernandez-Ruiz, Wei Lu, Ignacio Wistuba, John V. Heymach, Michael Chisamore, David Micklem, Hani Gabra, Gro Gausdal, James B. Lorens, Bo Li, Yang-Xin Fu, John D. Minna, Rolf A. Brekken
Journal: Cell Reports Medicine (2022)

Mutations in STK11/LKB1 in non-small cell lung cancer (NSCLC) are associated with poor patient responses to immune checkpoint blockade (ICB), and introduction of a Stk11/Lkb1 (L) mutation into murine lung adenocarcinomas driven by mutant Kras and Trp53 loss (KP) resulted in an ICB refractory syngeneic KPL tumor. Mechanistically this occurred because KPL mutant NSCLCs lacked TCF1-expressing CD8 T cells, a phenotype recapitulated in human STK11/LKB1 mutant NSCLCs. Systemic inhibition of Axl results in increased type I interferon secretion from dendritic cells that expanded tumor-associated TCF1+PD-1+CD8 T cells, restoring therapeutic response to PD-1 ICB in KPL tumors. This was observed in syngeneic immunocompetent mouse models and in humanized mice bearing STK11/LKB1 mutant NSCLC human tumor xenografts. NSCLC-affected individuals with identified STK11/LKB1 mutations receiving bemcentinib and pembrolizumab demonstrated objective clinical response to combination therapy. We conclude that AXL is a critical targetable driver of immune suppression in STK11/LKB1 mutant NSCLC.
IN-HOSPITAL OUTCOMES OF CATHETER-DIRECTED THROMBOLYSIS WITH ANTICOAGULATION IN CHRONIC KIDNEY DISEASE PATIENTS WITH PROXIMAL DEEP VENOUS THROMBOSIS - INSIGHTS FROM NATIONAL READMISSIONS DATABASE
Authors: Austin Quimby, Irfan Shafi, Maninder Singh, Vladimir Lakhter, Huaqing Zhao, Riyaz Bashir
Journal: Journal of the American College of Cardiology (2022)
ECSTACY INDUCED ACUTE MYOCARDIAL INFARCTION: ROLE OF MULTIMODALITY IMAGING
Authors: Glenmore U. Lasam, Loba Alam, Linus Nweke, Maria Pena, Petra Zubin Maslov, Robert Leber, Edgar Argulian, Soheila Talebi
Journal: Journal of the American College of Cardiology (2022)
VP2-2022: Prospective double-blind, randomized phase III ENGOT-EN5/GOG-3055/SIENDO study of oral selinexor/placebo as maintenance therapy after first-line chemotherapy for advanced or recurrent endometrial cancer
Authors: I.B. Vergote, A. Pérez Fidalgo, E. Hamilton, G. Valabrega, T. Van Gorp, J. Sehouli, D. Cibula, T. Levy, S. Welch, D.L. Richardson, E.M. Guerra Alía, G. Scambia, S. Henry, P. Wimberger, D. Miller, J. Martínez, B.J. Monk, S. Shacham, M.R. Mirza, V. Makker
Journal: Annals of Oncology (2022)
Behind the Hospital Curtain
Authors: Ryan Peters
Journal: JAMA Cardiology (2022)

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 Cardiology 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 Cardiology journal
PREDICTORS OF FUNCTIONAL MITRAL REGURGITATION IN PATIENTS WITH NON-ISCHEMIC CARDIOMYOPATHY: A CARDIAC MRI STUDY
Authors: Donna Salam, Tom Kai Ming Wang, Mustafa Turkmani, Samir R. Kapadia, Amar Krishnaswamy, Brian P. Griffin, Scott D. Flamm, Wai Hong Wilson Tang, Deborah Kwon
Journal: Journal of the American College of Cardiology (2022)
SAFETY AND FEASIBILITY OF PERCUTANEOUS MITRAL BALLOON VALVULOPLASTY IN PATIENTS WITH SEVERE MITRAL STENOSIS SECONDARY TO SEVERE MITRAL ANNULAR CALCIFICATION
Authors: Marissa Donatelle, Pradyumna Agasthi, Steve Xydas, Christos Mihos, Martin B. Leon, Nirat Beohar
Journal: Journal of the American College of Cardiology (2022)
Transmission of SARS-CoV-2 from mother to baby is rare
Authors: Catherine McLean Pirkle
Journal: BMJ (2022)

Since the start of the covid-19 pandemic, healthcare professionals have struggled to provide practical evidence based guidance for pregnant women and new parents about the harms babies and young children face from infection with SARS-CoV-2.Counselling parents about what to do if they become infected and the extent to which this might put their babies at risk is particularly challenging.For new mothers, in particular, providers need to counsel appropriately on the risks associated with breastfeeding and skin-to-skin contact, and, in some circumstances, whether or not to separate mother and baby at birth.
Clinical results of a 10-year follow-up of surgical treatment for elbow stiffness in rheumatoid arthritis: A case series
Authors: Wenjun Liu, Jingwei Zhang, Jiazhi Liu, Hao Xiong, Wei Wang, Yun Qian, Cunyi Fan
Journal: International Journal of Surgery (2022)

Rheumatoid arthritis commonly causes transient limitation of joint motion, but the treatment of persistent stiffness in the rheumatoid elbow has rarely been reported. The purpose of this study was to evaluate the long-term clinical results of surgical treatment of rheumatoid elbow stiffness. Surgical treatment, including open arthrolysis with hinged external fixation, total synovectomy, and ulnar nerve release and anteriorization, was performed in 48 elbows in 43 patients with rheumatoid arthritis and early joint destruction. Mobility (flexion-extension and pronation-supination), Mayo Elbow Performance Score (MEPS), visual analog scale (VAS) score, muscle strength, nerve symptoms, postoperative complications, and recurrent synovitis were evaluated 9–11 years (average, 9.88 years) postoperatively. The mobility of the elbow was significantly improved over the preoperative period either in extension, flexion, protonation, supination (P < .001, P < .001, P < .001, P = .002). The mean MEPS was significantly improved from 56.25 points (range, 30–90) to 87.40 points (range, 40–100) (P < .001). The pain was relieved, and the mean VAS score was reduced from 3.56 (range, 0–8) to 1.08 (range, 0–5) points (P < .001). Preoperative ulnar nerve symptoms were observed in 17 patients and relieved in 10 (59%) patients, and the mean Amadio score was raised from 6.9 (range, 3–9) to 7.96 (range, 4–9) points (P < .001). Through surgical treatment and postoperative rehabilitation, the mean grip strength of the patients was significantly improved from an average of 9.01 (range, 3.4–18.5) to 17.56 kg (range, 3.9–40.2) (P < .001). Five elbows developed recurrent synovitis, and one underwent total elbow arthroplasty. Postoperative complications were uncommon and not severe. Surgical treatment is a reliable procedure for rheumatoid elbow stiffness and can be effective in improving elbow mobility, function, muscle strength, pain relief, and relief of nerve symptoms.
INDIRECT TRANSFER TO CATHETERIZATION LABORATORY FOR ST ELEVATION MYOCARDIAL INFARCTION IS ASSOCIATED WITH MORTALITY INDEPENDENT OF SYSTEM DELAYS: INSIGHTS FROM THE FRANCE-PCI REGISTRY
Authors: Farzin Beygui, Fabrice Ivanes, Vincent Roule, Thierry Dechery, Laurent Roussel, Philippe Dequenne, Marc Antoine Arnould, Nicolas Combaret, Jean-Philippe Collet, Philippe Commeau, Guillaume Cayla, Gilles Montalescot, Hakim Benamer, Pascal Motreff, Denis Angoulvant, Pierre Marcollet, Stephan Chassaing, Katrien Blanchart, Rene Koning, Gregoire Range
Journal: Journal of the American College of Cardiology (2022)
Abstract P5-06-15: Enabling therapeutic decisions for a breast cancer patient cohort using matched diseased and normal tissue in tumor organoids
Authors: Liam Deems, Dmitry Shvartsman, Maria Ivanova, Cheryl Murphy, David Deems
Journal: Cancer Research (2022)

Abstract Pre-clinical cancer studies have been limited by the availability of patient cell models that accurately represent the diversity of patient populations. The utility of these studies is further impacted by the lack of normal tissue from the same patient. Furthermore, clinical evaluation of targeted therapeutics, like tarceva (erlotinib), would benefit from patient models expressing the target for robust characterization of drug response. Moreover, individual patient responses to the same anti-cancer compound cannot be assessed with high precision unless healthy controls are used from the same tumor donor. Here, we present six breast cancer patient-derived tumor models, accompanied by cancer (tumor)-associated fibroblasts (CAFs) and mesenchymal stem cells (MSCs). These paired and matched sample cohorts were studied in the context of spheroid models of the metastatic breast cancer niche. We show that these models allow an increased understanding of chemotherapy modulation by non-cancerous cells, which are present within the tumor but not targeted by the current chemotherapies or other anti-tumor approaches. We used a three-drug set to create a viability profile for each patient-associated tumor sample, which in turn can be used to aid clinical decision-making and increase the personalization of each treatment for an individual. Further, our approach shows different genomic and proteomic profiles for the co-culture models when compared between the tumor 3D and healthy controls. Citation Format: Liam Deems, Dmitry Shvartsman, Maria Ivanova, Cheryl Murphy, David Deems. Enabling therapeutic decisions for a breast cancer patient cohort using matched diseased and normal tissue in tumor organoids [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-06-15.
Preclinical Development and Evaluation of Allogeneic CAR T Cells Targeting CD70 for the Treatment of Renal Cell Carcinoma
Authors: Siler H. Panowski, Surabhi Srinivasan, Nguyen Tan, Silvia K. Tacheva-Grigorova, Bryan Smith, Yvonne S.L. Mak, Hongxiu Ning, Jonathan Villanueva, Dinali Wijewarnasuriya, Shanshan Lang, Zea Melton, Adit Ghosh, Mathilde Dusseaux, Roman Galetto, Jonathan R. Heyen, Tao Sai, Thomas Van Blarcom, Javier Chaparro-Riggers, Barbra J. Sasu
Journal: Cancer Research (2022)

CD70 is highly expressed in renal cell carcinoma (RCC), with limited expression in normal tissue, making it an attractive CAR T target for an immunogenic solid tumor indication. Here we generated and characterized a panel of anti-CD70 single-chain fragment variable (scFv)-based CAR T cells. Despite the expression of CD70 on T cells, production of CAR T cells from a subset of scFvs with potent in vitro activity was achieved. Expression of CD70 CARs masked CD70 detection in cis and provided protection from CD70 CAR T cell-mediated fratricide. Two distinct classes of CAR T cells were identified with differing memory phenotype, activation status, and cytotoxic activity. Epitope mapping revealed that the two classes of CARs bind unique regions of CD70. CD70 CAR T cells displayed robust antitumor activity against RCC cell lines and patient-derived xenograft mouse models. Tissue cross-reactivity studies identified membrane staining in lymphocytes, thus matching the known expression pattern of CD70. In a cynomolgus monkey CD3-CD70 bispecific toxicity study, expected findings related to T-cell activation and elimination of CD70-expressing cells were observed, including cytokine release and loss of cellularity in lymphoid tissues. Finally, highly functional CD70 allogeneic CAR T cells were produced at large scale through elimination of the T-cell receptor by TALEN-based gene editing. Taken together, these efficacy and safety data support the evaluation of CD70 CAR T cells for the treatment of RCC and has led to the advancement of an allogeneic CD70 CAR T-cell candidate into phase I clinical trials.These findings demonstrate the efficacy and safety of fratricide-resistant, allogeneic anti-CD70 CAR T cells targeting renal cell carcinoma and the impact of CAR epitope on functional activity. See related commentary by Adotévi and Galaine, p. 2517.
Preclinical studies of Flonoltinib Maleate, a novel JAK2/FLT3 inhibitor, in treatment of JAK2V617F-induced myeloproliferative neoplasms
Authors: Mengshi Hu, Tao Yang, Linyu Yang, Lu Niu, Jinbing Zhu, Ailin Zhao, Mingsong Shi, Xue Yuan, Minghai Tang, Jianhong Yang, Heying Pei, Zhuang Yang, Qiang Chen, Haoyu Ye, Ting Niu, Lijuan Chen
Journal: Blood Cancer Journal (2022)

Abstract Janus kinase 2 (JAK2) hyperactivation by JAK2 V617F mutation leads to myeloproliferative neoplasms (MPNs) and targeting JAK2 could serve as a promising therapeutic strategy for MPNs. Here, we report that Flonoltinib Maleate (FM), a selective JAK2/FLT3 inhibitor, shows high selectivity for JAK2 over the JAK family. Surface plasmon resonance assays verified that FM had a stronger affinity for the pseudokinase domain JH2 than JH1 of JAK2 and had an inhibitory effect on JAK2 JH2V617F. The cocrystal structure confirmed that FM could stably bind to JAK2 JH2, and FM suppressed endogenous colony formation of primary erythroid progenitor cells from patients with MPNs. In several JAK2 V617F -induced MPN murine models, FM could dose-dependently reduce hepatosplenomegaly and prolong survival. Similar results were observed in JAK2 V617F bone marrow transplantation mice. FM exhibited strong inhibitory effects on fibrosis of the spleen and bone marrow. Long-term FM treatment showed good pharmacokinetic/pharmacodynamic characteristics with high drug exposure in tumor-bearing tissues and low toxicity. Currently, FM has been approved by the National Medical Products Administration of China (CXHL2000628), and this study will guide clinical trials for patients with MPNs.
PHOSPHORYLATION AND FRAGMENTATION PATTERN OF CARDIAC MYOSIN-BINDING PROTEIN C FOR THE DIFFERENTIATION BETWEEN DIFFERENT TYPES OF MYOCARDIAL INJURY
Authors: Bashir Alaour, Yu Jin Chung, Thomas Edward Kaier, Jasmine India Helen Quraishi, Helen Heath, Zilan Demir, Sakthivel Sadayappan, Simon R. Redwood, Brian Raymond Weil, John M. Canty, Michael S. Marber
Journal: Journal of the American College of Cardiology (2022)
Abstract P1-10-06: Effect of aging and mTOR inhibition on human mammary stem cells and early breast cancer progression markers
Authors: Larry E Broome, Hakim Bouamar, Kate Lathrop, Ismail Jatoi, Andrew Brenner, Michael Garcia, Alia Nazarullah, Karla Moncada, Virginia Kaklamani, Lu-Zhe Sun
Journal: Cancer Research (2022)

Abstract Ductal carcinoma in situ (DCIS) is the most common form of breast cancer and is a predecessor to invasive carcinoma development. The origins for early breast cancer have been attributed to aberrant single cells, which may include adult stem and progenitor cells. We performed a window trial with mTOR inhibitor sirolimus in patients with atypical ductal hyperplasia (ADH) or DCIS and investigated the epithelial populations in adjacent normal and ADH/DCIS breast tissues along with their residing stem and progenitor cell activity. Differences associated with age, menopausal status, and treatment by sirolimus have also been explored. While the mammary epithelial populations were seen to be unchanged in aging, we found that age correlates with a decline in stem cell activity. mTOR inhibition was also able to abrogate mammary stem cell activity and decrease luminal progenitor passaging lifespan, particularly in postmenopausal patients. While mTOR inhibition had no effect on myoepithelial populations, it did decrease premenopausal luminal cell populations and reduced prognostic markers associated with breast cancer progression from DCIS to invasive breast cancer. These markers include p16INK4A, COX-2, and Ki67, which were reduced in DCIS breast tissue from patients administered with sirolimus as shown through quantitative analysis of immunohistochemistry. Overall, these findings indicate a link from mTOR signaling to mammary stem cell activity and cancer progression. mTOR inhibitors may have potential for breast cancer prevention. Citation Format: Larry E Broome, Hakim Bouamar, Kate Lathrop, Ismail Jatoi, Andrew Brenner, Michael Garcia, Alia Nazarullah, Karla Moncada, Virginia Kaklamani, Lu-Zhe Sun. Effect of aging and mTOR inhibition on human mammary stem cells and early breast cancer progression markers [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-10-06.
CARDIOVASCULAR COMORBIDITIES PREDISPOSE TO CARDIOVASCULAR COMPLICATIONS IN HOSPITALIZED PATIENTS WITH COVID-19 INFECTION
Authors: Shadi Razipour, Abdel Hadi El Hajjar, Christopher Pottle, Chan Ho Lim, Yichi Zhang, Noor Makan, Mario Mekhael, Tarek Hassan Ayoub, Charbel Noujaim, Zaina Abdel Karim, Nassir F. Marrouche
Journal: Journal of the American College of Cardiology (2022)
EFFECTS OF SGLT2 INHIBITORS ON LEFT VENTRICULAR MASS, VOLUME AND FUNCTION IN PATIENTS WITH HEART FAILURE AND REDUCED EJECTION FRACTION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED STUDIES
Authors: Francisco Romeo, Marco Giuseppe Del Buono, Juan Ignacio Damonte, Juan Guido Chiabrando, Jose S. Aguilar-Gallardo, Marta Lorente-Ros, Salvatore Carbone, Antonio Abbate
Journal: Journal of the American College of Cardiology (2022)
TARGETING SYNCHRONIZED ELECTROGRAM ISLANDS WITHIN ATRIAL FIBRILLATION FOR ABLATION
Authors: Prasanth Ganesan, Brototo Deb, Ruibin Feng, Miguel Rodrigo, Samuel Ruiperez-Campillo, Neal K. Bhatia, Albert J. Rogers, Paul Clopton, Wouter-Jan Rappel, Sanjiv M. Narayan
Journal: Journal of the American College of Cardiology (2022)
Targeting adaptive radioresistance in glioblastoma
Authors: Satoru Osuka
Journal: Neuro-Oncology (2022)

Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis.1 Radiotherapy is effective for GBM and is used as a standard treatment. However, its effect is temporary and not sufficient to prevent recurrence.2 Therefore, research is ongoing to identify mechanisms of radioresistance and develop new treatments to increase the radiation sensitivity of GBM. Past studies showed that cells with stem cell properties and mesenchymal phenotype play an essential role in radioresistance3,4; however, no effective treatment has been developed for radioresistant GBM cells. A subpopulation of tumor cells in a pre-treatment GBM display innate radioresistance due to preexisting genetic mutations that activate resistance pathways and these cells can expand after treatment. Tumor cells can also become resistant by progressively adapting to repeated radiotherapy, a process called adaptive radioresistance (Figure 1A).2,3,5 The mechanisms of adaptive radioresistance of GBM cells are still not well understood. Intrinsic mechanisms of resistance can be analyzed by looking at cell survival after a single dose of radiation; however, studying adaptive mechanisms requires experimental models using long-term fractionated irradiation. Past studies using models with fractionated irradiation have shown that GBM cells increase their radioresistance through dynamic alteration of cellular characteristics, including stemness, mesenchymal change, and DNA damage repair.3,5 Adaptive radioresistance can be triggered by changes in gene expression through epigenetic changes, alternative splicing, and posttranslational protein modifications. This reprogramming can occur through signals of the tumor environment or stochastic intracellular events. Prior studies have evidenced signaling modifications in IGF-1R, Akt, and N-cadherin.2,3,5
EFFICACY OF ERTUGLIFLOZIN ON HEART FAILURE HOSPITALIZATION AND HF DEATH ACROSS THE WATCH-DM RISK SCORE: A SECONDARY ANALYSIS OF THE VERTIS CV TRIAL
Authors: Matthew Segar, Darren K. McGuire, Robert Frederich, David Z.I. Cherney, Christopher P. Cannon, Francesco Cosentino, Samuel Dagogo-Jack, Richard Pratley, Nilo B. Cater, Mario Maldonado, Birol Emir, Darren Jeng, Harry Shi, Ambarish Pandey
Journal: Journal of the American College of Cardiology (2022)
Diagnostic, prognostic and differential-diagnostic relevance of pulmonary haemodynamic parameters during exercise: a systematic review
Authors: Katarina Zeder, Chiara Banfi, Gregor Steinrisser-Allex, Bradley A. Maron, Marc Humbert, Gregory D. Lewis, Andrea Berghold, Horst Olschewski, Gabor Kovacs
Journal: European Respiratory Journal (2022)

Background The cardiopulmonary haemodynamic profile observed during exercise may identify patients with early-stage pulmonary vascular and primary cardiac diseases, and is used clinically to inform prognosis. However, a standardised approach to interpreting haemodynamic parameters is lacking. Methods We performed a systematic literature search according to PRISMA guidelines to identify parameters that may be diagnostic for an abnormal haemodynamic response to exercise and offer optimal prognostic and differential-diagnostic value. We performed random-effects meta-analyses of the normal values and report effect sizes as weighted mean± sd . Results of diagnostic and prognostic studies are reported descriptively. Results We identified 45 eligible studies with a total of 5598 subjects. The mean pulmonary arterial pressure (mPAP)/cardiac output (CO) slope, pulmonary arterial wedge pressure (PAWP)/CO slope and peak cardiac index (or CO) provided the most consistent prognostic haemodynamic parameters during exercise. The best cut-offs for survival and cardiovascular events were a mPAP/CO slope &gt;3 Wood units (WU) and PAWP/CO slope &gt;2 WU. A PAWP/CO slope cut-off &gt;2 WU best differentiated pre- from post-capillary causes of PAP elevation during exercise. Upper limits of normal (defined as mean+2 sd ) for the mPAP/CO and PAWP/CO slopes were strongly age-dependent and ranged in 30–70-year-old healthy subjects from 1.6 to 3.3 WU and 0.6 to 1.8 WU, respectively. Conclusion An increased mPAP/CO slope during exercise is associated with impaired survival and an independent, prognostically relevant cut-off &gt;3 WU has been validated. A PAWP/CO slope &gt;2 WU may be suitable for the differentiation between pre- and post-capillary causes of PAP increase during exercise.