tbuckley/cabot-search huggingface dataset:
Infant brain tumor trials: Beyond feasibility
Authors: Eric Bouffet, Lucie Lafay-Cousin
Journal: Neuro-Oncology (2022)

The management of infants and young children with embryonal tumors of the central nervous system (CNS) remains a major challenge. Early cooperative trials conducted 4 decades ago were designed with the aim to delay the use of craniospinal radiotherapy until the age of 3 years. These trials showed a high rate of progression, usually early during the course of chemotherapy, and as a consequence, a high proportion of these patients received salvage radiotherapy for a 3-year overall survival (OS) ranging between 20% and 50% depending on the type of embryonal tumor. Subsequent trials have explored various concepts, including the use of more intensive chemotherapy and high-dose chemotherapy with autologous bone marrow or stem cell transplant, the administration of intrathecal or intraventricular chemotherapy, the addition of focal irradiation or reduced-dose craniospinal irradiation (CSI) as well as the addition of maintenance chemotherapy. Although progress has been achieved, the outcome of children with embryonal tumors of the CNS remains—with the exception of children with desmoplastic medulloblastoma (MB)—globally unsatisfactory and new treatment modalities are urgently needed. Leary et al report the results of a pilot study, PBTC-026, that tested the feasibility of adding non-cytotoxic agents (vorinostat and isotretinoin) to a sequential high-dose chemotherapy backbone for young children with CNS embryonal tumors.1 The rationale for this combination was essentially based on data supporting the activity and the synergism of the 2 compounds in preclinical models of MB.
THE IMPACT OF COAPTATION RESERVE AND ADDRESSABLE COAPTATION AREA FOR OPTIMAL REDUCTION IN MITRAL REGURGITATION AND LONG-TERM SURVIVAL WITH TRANSCATHETER EDGE-TO-EDGE REPAIR
Authors: Hirotomo Sato, Joao L. Cavalcante, Richard Y. Bae, Vinayak Nilkanth Bapat, Garcia Santiago, Mario Goessl, Go Hashimoto, Miho Fukui, Maurice Enriquez-Sarano, Paul Sorajja
Journal: Journal of the American College of Cardiology (2022)
ASSOCIATION BETWEEN LEFT VENTRICULAR EJECTION FRACTION AND LIPID CORE BURDEN INDEX IN PREDIABETIC PATIENTS.
Authors: Mairita Karantajere, Evija Knoka, Laima Caunite, Maris Lapsovs, Matiss Karantajers, Sanda Jegere, Indulis Kumsars, Inga Narbute, Ieva Briede, Karlis Trusinskis, Andrejs Erglis
Journal: Journal of the American College of Cardiology (2022)
CLO22-050: Hospitalization and Supportive Care Medication (SCM) Utilization in Patients (pts) With Advanced Non-Small Cell Lung Cancer (aNSCLC) in EMPOWER-Lung 1
Authors: Mahmut Gümüş, Ahmet Sezer, Eric Yan, Saadettin Kilickap, Igor Bondarenko, Mustafa Özgüroğlu, Miranda Gogishvili, Giuseppe Gullo, Petra Rietschel, Ruben GW Quek
Journal: Journal of the National Comprehensive Cancer Network (2022)

"CLO22-050: Hospitalization and Supportive Care Medication (SCM) Utilization in Patients (pts) With Advanced Non-Small Cell Lung Cancer (aNSCLC) in EMPOWER-Lung 1" published on 31 Mar 2022 by National Comprehensive Cancer Network.
Re: Christopher Soliman, Niranjan J. Sathianathen, Gianluca Giannarini, et al. There is a Need for a Universal Language in the Reporting and Grading of Complication and Intervention Events to Ensure Comparability and Improvement of Surgical Care. Eur Urol. 2022;81:440–5.
Authors: Mara Koelker, Michael Rink, Malte W. Vetterlein
Journal: European Urology (2022)
Commemorating World Tuberculosis Day 2022: recent <i>ERJ</i> articles of critical relevance to ending TB and saving lives
Authors: Giovanni Battista Migliori, Dennis Falzon, Guy B. Marks, Delia Goletti, Tereza Kasaeva, Susanna Esposito, Marc Humbert
Journal: European Respiratory Journal (2022)

Tuberculosis (TB) remains a major public health concern worldwide. In 2020, it was the 13th leading cause of death and the second leading infectious killer after coronavirus disease 2019 (COVID-19), above HIV/AIDS. In 2020 a total of 1.5 million people died from TB, while about 10 million people are estimated to have suffered from the disease: 5.6 million men, 3.3 million women and 1.1 million children [1]. The ERJ commemorates World TB Day 2022 by publishing relevant articles to contribute to the fight against tuberculosis <https://bit.ly/3gNby7P>
Tether-free photothermal deep-brain stimulation in freely behaving mice via wide-field illumination in the near-infrared-II window
Authors: Xiang Wu, Yuyan Jiang, Nicholas J. Rommelfanger, Fan Yang, Qi Zhou, Rongkang Yin, Junlang Liu, Sa Cai, Wei Ren, Andrew Shin, Kyrstyn S. Ong, Kanyi Pu, Guosong Hong
Journal: Nature Biomedical Engineering (2022)
PROGNOSTIC SIGNIFICANCE OF PULMONARY HYPERTENSION IN PATIENTS WITH OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY AFTER SEPTAL MYECTOMY
Authors: Aaron Lee, Xianying Liu, Michael Yaoyao Yin, Daniel Patrick McGrath, Kelly Ohlrich, Navin Kapur, Michael Robich
Journal: Journal of the American College of Cardiology (2022)
Vaccine breakthrough infections with SARS-CoV-2 Alpha mirror mutations in Delta Plus, Iota, and Omicron
Authors: Brenda Martínez-González, Lucía Vázquez-Sirvent, María E. Soria, Pablo Mínguez, Llanos Salar-Vidal, Carlos García-Crespo, Isabel Gallego, Ana I. de Ávila, Carlos Llorens, Beatriz Soriano, Ricardo Ramos-Ruiz, Jaime Esteban, Ricardo Fernandez-Roblas, Ignacio Gadea, Carmen Ayuso, Javier Ruíz-Hornillos, Concepción Pérez-Jorge, Esteban Domingo, Celia Perales
Journal: Journal of Clinical Investigation (2022)

Replication of SARS-CoV-2 in the human population is defined by distributions of mutants that are present at different frequencies within the infected host and can be detected by ultra-deep sequencing techniques. In this study, we examined the SARS-CoV-2 mutant spectra of amplicons from the spike-coding (S-coding) region of 5 nasopharyngeal isolates derived from patients with vaccine breakthrough. Interestingly, all patients became infected with the Alpha variant, but amino acid substitutions that correspond to the Delta Plus, Iota, and Omicron variants were present in the mutant spectra of the resident virus. Deep sequencing analysis of SARS-CoV-2 from patients with vaccine breakthrough revealed a rich reservoir of mutant types and may also identify tolerated substitutions that can be represented in epidemiologically dominant variants.
DREAM-ICD-II Study
Authors: Christian Steinberg, Nicolas Dognin, Amit Sodhi, Catherine Champagne, John A. Staples, Jean Champagne, Zachary W. Laksman, Jean-François Sarrazin, Matthew T. Bennett, Benoit Plourde, Marc W. Deyell, Jason G. Andrade, Karine Roy, John A. Yeung-Lai-Wah, Nathaniel M. Hawkins, Blandine Mondésert, Louis Blier, Isabelle Nault, Gilles O’Hara, Andrew D. Krahn, François Philippon, Santabhanu Chakrabarti
Journal: Circulation (2021)

Background: Regulatory authorities of most industrialized countries recommend 6 months of private driving restriction after implantation of a secondary prevention implantable cardioverter-defibrillator (ICD). These driving restrictions result in significant inconvenience and social implications. This study aimed to assess the incidence rate of appropriate device therapies in contemporary recipients of a secondary prevention ICD. Methods: This retrospective study at 3 Canadian tertiary care centers enrolled consecutive patients with new secondary prevention ICD implants between 2016 and 2020. Results: For a median of 760 days (324, 1190 days), 721 patients were followed up. The risk of recurrent ventricular arrhythmia was highest during the first 3 months after device insertion (34.4%) and decreased over time (10.6% between 3 and 6 months, 11.7% between 6 and 12 months). The corresponding incidence rate per 100 patient-days was 0.48 (95% CI, 0.35–0.64) at 90 days, 0.28 (95% CI, 0.17–0.45) at 180 days, and 0.21 (95% CI, 0.13–0.33) between 181 and 365 days after ICD insertion ( P &lt;0.001). The cumulative incidence of arrhythmic syncope resulting in sudden cardiac incapacitation was 1.8% within the first 90 days and subsequently dropped to 0.4% between 91 and 180 days ( P &lt;0.001) after ICD insertion. Conclusions: The incidence rate of appropriate therapies resulting in sudden cardiac incapacitation in contemporary recipients of a secondary prevention ICD is much lower than previously reported and declines significantly after the first 3 months. Lowering driving restrictions to 3 months after the index cardiac event seems safe, and revision of existing guidelines should be considered in countries still adhering to a 6-month period. Existing restrictions for private driving after implantation of a secondary prevention ICD should be reconsidered.
Macrophage compartmentalization in the brain and cerebrospinal fluid system
Authors: David A. D. Munro, Kiavash Movahedi, Josef Priller
Journal: Science Immunology (2022)

Macrophages reside within the diverse anatomical compartments of the central nervous system (CNS). Within each compartment, these phagocytes are exposed to unique combinations of niche signals and mechanical stimuli that instruct their tissue-specific identities. Whereas most CNS macrophages are tissue-embedded, the macrophages of the cerebrospinal fluid (CSF) system are bathed in an oscillating liquid. Studies using multiomics technologies have recently uncovered the transcriptomic and proteomic profiles of CSF macrophages, enhancing our understanding of their cellular characteristics in both rodents and humans. Here, we review the relationships between CNS macrophage populations, with a focus on the origins, phenotypes, and functions of CSF macrophages in health and disease.
WHIPPLE-ING IN THE VALVES: TROPHERYMA WHIPPLEI BIOPROSTHETIC VALVE INFECTIVE ENDOCARDITIS REQUIRING REPLACEMENT AND AORTIC ROOT GRAFTING COMPLICATED BY HEART BLOCK
Authors: Marvyn Allen Chan, David Gruen, Patrick Benjamin, Olamide Oyenubi, Bisrat Teweldemedhin, Gerald Kristoffer E. Boy, Thomas J. Pettei
Journal: Journal of the American College of Cardiology (2022)
Neuroimmune Interactions in Peripheral Organs
Authors: Roel G.J. Klein Wolterink, Glendon S. Wu, Isaac M. Chiu, Henrique Veiga-Fernandes
Journal: Annual Review of Neuroscience (2022)

Interactions between the nervous and immune systems were recognized long ago, but recent studies show that this crosstalk occurs more frequently than was previously appreciated. Moreover, technological advances have enabled the identification of the molecular mediators and receptors that enable the interaction between these two complex systems and provide new insights on the role of neuroimmune crosstalk in organismal physiology. Most neuroimmune interactions occur at discrete anatomical locations in which neurons and immune cells colocalize. Here, we describe the interactions of the different branches of the peripheral nervous system with immune cells in various organs, including the skin, intestine, lung, and adipose tissue. We highlight how neuroimmune crosstalk orchestrates physiological processes such as host defense, tissue repair, metabolism, and thermogenesis. Unraveling these intricate relationships is invaluable to explore the therapeutic potential of neuroimmune interactions.
CORONARY MICROVASCULAR HEALTH IN PATIENTS WITH PRIOR COVID-19 INFECTION: IMPLICATIONS FOR LONG-COVID SYNDROME
Authors: Ahmed Ibrahim Ahmed, Jean Michel Saad, Yushui Han, Maan Malahfji, Faisal Nabi, John J. Mahmarian, William A. Zoghbi, Mouaz H. Al-Mallah
Journal: Journal of the American College of Cardiology (2022)
Genetic variation within the human papillomavirus type 16 genome is associated with oropharyngeal cancer prognosis
Authors: K.A. Lang Kuhs, D.L. Faden, L. Chen, D.K. Smith, M. Pinheiro, C.B. Wood, S. Davis, M. Yeager, J.F. Boland, M. Cullen, M. Steinberg, S. Bass, X. Wang, P. Liu, M. Mehrad, T. Tucker, J.S. Lewis, R.L. Ferris, L. Mirabello
Journal: Annals of Oncology (2022)
Numeric Errors in Results, Table, and Figures 2-4
Authors: Matthew Mcdonough, Jordan Dimitrakoff
Journal: JAMA Surgery (2022)

Javier Ripollés-Melchor, MD; José M Ramírez-Rodríguez, PhD; Rubén Casans-Francés, PhD; César Aldecoa, PhD; Ane Abad-Motos, MD; Margarita Logroño-Egea, MD; José Antonio García-Erce, PhD; Ángels Camps-Cervantes, MD; Carlos Ferrando-Ortolá, PhD; Alejandro Suarez de la Rica, PhD; Ana Cuellar-Martínez, MD; Sandra Marmaña-Mezquita, MD; Alfredo Abad-Gurumeta, PhD; José M. Calvo-Vecino, PhD; POWER Study Investigators Group for the Spanish Perioperative Audit and Research Network (REDGERM)
SEX-SPECIFIC STUDY ON THE COLLATERAL EFFECT OF COVID-19 PANDEMIC
Authors: Kamile Cerlinskaite-Bajore, Vilhelmas Bajoras, Rasa Visinskiene, Mindaugas Lizaitis, Povilas Budrys, Romualdas Gurevicius, Pranas Serpytis, Giedrius Davidavicius, Jelena Celutkiene
Journal: Journal of the American College of Cardiology (2022)
PREVALENCE OF ISCHEMIA ON STRESS ECHOCARDIOGRAPHY OR NUCLEAR IMAGING IN PATIENTS WITH ANOMALOUS LEFT CORONARY ARTERY ARISING FROM THE OPPOSITE SINUS OF VALSALVA
Authors: Mary-Tiffany A. Oduah, Nandan Sadanand Anavekar, Heidi M. Connolly, William R. Miranda
Journal: Journal of the American College of Cardiology (2022)
Noncoding RNAs in age-related cardiovascular diseases
Authors: Amela Jusic, Pınar Buket Thomas, Stephanie Bezzina Wettinger, Soner Dogan, Rosienne Farrugia, Carlo Gaetano, Bilge Güvenç Tuna, Florence Pinet, Emma L. Robinson, Simon Tual-Chalot, Konstantinos Stellos, Yvan Devaux
Journal: Ageing Research Reviews (2022)
Bone Tuberculous Granulomatous Inflammation Mimicking Malignancy on 68Ga-FAPI PET/CT
Authors: Weidong Gong, Xiao Yang, Chunru Mou, Huipan Liu, Chunyin Zhang
Journal: Clinical Nuclear Medicine (2022)

Abstract A 50-year-old woman presented with back pain for 1 month. Chest CT showed osteolytic destruction of T6 vertebral body. A malignancy was suspected. The patient was subsequently enrolled in the clinical trial of 68 Ga-FAPI PET/CT. 68 Ga-FAPI PET/CT revealed multiple bone destruction with increased FAPI activity. It was also highly suggestive of malignancy or metastases. However, pathological examination after T6 vertebral surgery confirmed the diagnosis of tuberculous granulomatous inflammation.
<scp>SARS‐CoV</scp>‐2 vaccination in patients with paroxysmal nocturnal hemoglobinuria: An Italian multicenter survey
Authors: Juri Alessandro Giannotta, Bruno Fattizzo, Marta Bortolotti, Corrado Girmenia, Claudia Ielo, Elisabetta Metafuni, Adele Visentin, Vincenzo Apolito, Alessandro Lucchesi, Valentina Giai, Eloise Beggiato, Eros Di Bona, Fabio Giglio, Simona Sica, Anna Paola Iori, Wilma Barcellini
Journal: American Journal of Hematology (2022)
T cell receptor engineering of primary NK cells to therapeutically target tumors and tumor immune evasion
Authors: Laura T Morton, Tassilo L A Wachsmann, Miranda H Meeuwsen, Anne K Wouters, Dennis F G Remst, Marleen M van Loenen, J H Frederik Falkenburg, Mirjam H M Heemskerk
Journal: Journal for ImmunoTherapy of Cancer (2022)

T cell receptor (TCR)-engineered cells can be powerful tools in the treatment of malignancies. However, tumor resistance by Human Leukocyte antigen (HLA) class I downregulation can negatively impact the success of any TCR-mediated cell therapy. Allogeneic natural killer (NK) cells have demonstrated efficacy and safety against malignancies without inducing graft-versus-host-disease, highlighting the feasibility for an 'off the shelf' cellular therapeutic. Furthermore, primary NK cells can target tumors using a broad array of intrinsic activation mechanisms. In this study, we combined the antitumor effector functions of NK cells with TCR engineering (NK-TCR), creating a novel therapeutic strategy to avoid TCR-associated immune resistance.BOB1, is a transcription factor highly expressed in all healthy and malignant B cell lineages, including multiple myeloma (MM). Expression of an HLA-B*07:02 restricted BOB1-specifc TCR in peripheral blood-derived NK cells was achieved following a two-step retroviral transduction protocol. NK-TCR was then compared with TCR-negative NK cells and CD8-T cells expressing the same TCR for effector function against HLA-B*07:02+ B-cell derived lymphoblastoid cell lines (B-LCL), B-cell acute lymphoblastic leukemia and MM cell lines in vitro and in vivo.Firstly, TCR could be reproducibly expressed in NK cells isolated from the peripheral blood of multiple healthy donors generating pure NK-TCR cell products. Secondly, NK-TCR demonstrated antigen-specific effector functions against malignancies which were previously resistant to NK-mediated lysis and enhanced NK efficacy in vivo using a preclinical xenograft model of MM. Moreover, antigen-specific cytotoxicity and cytokine production of NK-TCR was comparable to CD8 T cells expressing the same TCR. Finally, in a model of HLA-class I loss, tumor cells with B2M KO were lysed by NK-TCR in an NK-mediated manner but were resistant to T-cell based killing.NK-TCR cell therapy enhances NK cell efficacy against tumors through additional TCR-mediated lysis. Furthermore, the dual efficacy of NK-TCR permits the specific targeting of tumors and the associated TCR-associated immune resistance, making NK-TCR a unique cellular therapeutic.
MECHANICAL THROMBECTOMY IN A PATIENT WITH CONCURRENT PULMONARY EMBOLUS AND PATENT FORAMEN OVALE: THE UTILITY OF ECHOCARDIOGRAM WITH BUBBLE STUDY
Authors: Sharana Hegde, Eric Bucklew, Srikanth Radhakrishnan, Nazli Okumus, Adnan Khalif, Ali J. Noory, Mithun Chakravarthy
Journal: Journal of the American College of Cardiology (2022)
Selected Articles from This Issue
Journal: Clinical Cancer Research (2022)

Neratinib is an irreversible pan-HER inhibitor approved for patients with HER2 amplified breast cancer. MutHER trial evaluated the antitumor activity of neratinib and neratinib in combination with fulvestrant for HER2 non-amplified metastatic breast cancer harboring activating mutations in HER2, a population otherwise not eligible for HER2-targeted therapy. The study demonstrated the antitumor effect of neratinib, especially in invasive lobular breast cancer. Interestingly, responses were observed with the addition of trastuzumab to neratinib upon disease progression, suggesting dual HER2 blockade may be important in targeting HER2 mutation. Further investigation of trastuzumab in combination with neratinib is therefore warranted.Fusions involving the NTRK1/2/3 genes have been identified in many tumor types, several of which often metastasize to the CNS. Entrectinib is a potent TRK inhibitor that was specifically designed to penetrate and remain in the CNS. Demetri and colleagues present the latest results of an integrated analysis of three phase I/II trials: entrectinib continued to induce deep and durable systemic and intracranial responses across tumor types and was well tolerated. Entrectinib could address the need for a CNS-active treatment in NTRK fusion-positive solid tumors; therefore, encouraging broader NTRK fusion testing would improve patient access to effective, personalized treatments.Concurrent radiation therapy (RT) with cetuximab, an anti-EGFR monoclonal antibody (mAb), is a standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC); however, control in high-risk disease is suboptimal. CTLA-4+ T regulatory cells (Treg) dampen cellular immunity and correlate negatively with clinical outcomes. Ferris and colleagues conducted a phase I trial to evaluate the safety and preliminary efficacy of the CTLA-4 targeting mAb, ipilimumab, with standard, fixed cetuximab-RT. They identified the recommended phase II dose and observed acceptable PFS and OS without cytotoxic chemotherapy. High expression of coinhibitory receptors PD1/LAG3/CD39 on baseline tumor infiltrating Treg was marginally associated with worse PFS. This is the first trial to combine CTLA-4 targeting with definitive cetuximab-RT in HNSCC, integrating immune checkpoint inhibitors into curative-intent RT platforms.Otani and colleagues used immunofluorescence staining and RNA-seq to uncover a significant induction of MDSC cell populations into brains of tumor-bearing mice treated with oHSV. This was mediated by NOTCH induction. In human patients, NOTCH signaling also correlated with a higher myeloid cell infiltration. The tumor infiltrating myeloid cells further spread NOTCH signaling in tumors and also created a CCL-2 feed-forward loop to induce more myeloid cells into the tumors. Increased CCL2 was also observed in serum of GBM patients treated with oHSV. Blockade of NOTCH signaling rescued these immunosuppressive effects and enhanced antitumor immunity.
A CASE OF PERIPARTUM VENTRICULAR ARRHYTHMIA: DELIVERING OPTIMAL MULTIDISCIPLINARY CARE WHEN IT IS TIME TO DELIVER
Authors: Cecillia Y. Wong, Offdan Narvaez-Guerra, Lila Kaminsky, John Bartlett Dickey, Qi Zheng, Julianne Lauring, Leora Balsam, Mary Huerter, Colleen Harrington, Lara Kovell
Journal: Journal of the American College of Cardiology (2022)
Cost-effectiveness of ambulatory care management of primary spontaneous pneumothorax: an open-label, randomised controlled trial
Authors: Ramon Luengo-Fernandez, Filipa Landeiro, Rob Hallifax, Najib M Rahman
Journal: Thorax (2022)

Background Ambulatory management of primary spontaneous pneumothorax has been shown to reduce initial hospitalisation, but at the expense of increase adverse events. As a result, questions remain about the cost-effectiveness of this option. Objectives A within-trial economic evaluation alongside a randomised controlled trial was performed to assess the cost-effectiveness of ambulatory care when compared with standard guideline-based management. Methods Patients were randomly assigned to treatment with either an ambulatory device or standard guideline-based management (aspiration, standard chest tube insertion or both). Follow-up was 12 months. Outcomes included healthcare resource use and costs, quality of life, quality-adjusted life-years (QALYs) and cost-effectiveness. Results 236 patients were recruited and randomly assigned to ambulatory care (n=117) and standard care (n=119). After multiple imputation for missing data, patients in the ambulatory care group had significantly lower National Health Service healthcare costs (−£788, 95% CI difference: −1527 to −50; p=0.037) than those in the standard care group. There were no differences in the number of QALYs gained (mean difference: −0.001, 95% CI difference: −0.032 to 0.030; p=0.95). When standard care was compared with ambulatory care, the incremental cost-effectiveness ratio was £799 066 per QALY gained, well above current thresholds of cost-effectiveness. As a result, the probability of ambulatory care being cost-effective was 0.93. Conclusion Outpatient ambulatory management is highly likely to be a cost-effective option in the management of primary pneumothorax. Trial registration number ISRCTN79151659 .