tbuckley/cabot-search huggingface dataset:
CPX-351 exploits the gut microbiota to promote mucosal barrier function, colonization resistance, and immune homeostasis
Authors: Giorgia Renga, Emilia Nunzi, Claudia Stincardini, Marilena Pariano, Matteo Puccetti, Giuseppe Pieraccini, Claudia Di Serio, Maurizio Fraziano, Noemi Poerio, Vasileios Oikonomou, Paolo Mosci, Enrico Garaci, Luana Fianchi, Livio Pagano, Luigina Romani
Journal: Blood (2024)

Abstract CPX-351, a liposomal combination of cytarabine plus daunorubicin, has been approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes, because it improves survival and outcome of patients who received hematopoietic stem cell transplant compared with the continuous infusion of cytarabine plus daunorubicin (referred to as “7 + 3” combination). Because gut dysbiosis occurring in patients with AML during induction chemotherapy heavily affects the subsequent phases of therapy, we have assessed whether the superior activity of CPX-351 vs “7 + 3” combination in the real-life setting implicates an action on and by the intestinal microbiota. To this purpose, we have evaluated the impact of CPX-351 and “7 + 3” combination on mucosal barrier function, gut microbial composition and function, and antifungal colonization resistance in preclinical models of intestinal damage in vitro and in vivo and fecal microbiota transplantation. We found that CPX-351, at variance with “7 + 3” combination, protected from gut dysbiosis, mucosal damage, and gut morbidity while increasing antifungal resistance. Mechanistically, the protective effect of CPX-351 occurred through pathways involving both the host and the intestinal microbiota, namely via the activation of the aryl hydrocarbon receptor–interleukin-22 (IL-22)–IL-10 host pathway and the production of immunomodulatory metabolites by anaerobes. This study reveals how the gut microbiota may contribute to the good safety profile, with a low infection-related mortality, of CPX-351 and highlights how a better understanding of the host-microbiota dialogue may contribute to pave the way for precision medicine in AML.
Resistant Hypertension in Dialysis: Epidemiology, Diagnosis, and Management
Authors: Panagiotis I. Georgianos, Rajiv Agarwal
Journal: Journal of the American Society of Nephrology (2024)

Apparent treatment-resistant hypertension is defined as an elevated BP despite the use of ≥3 antihypertensive medications from different classes or the use of ≥4 antihypertensives regardless of BP levels. Among patients receiving maintenance hemodialysis or peritoneal dialysis, using this definition, the prevalence of apparent treatment-resistant hypertension is estimated to be between 18% and 42%. Owing to the lack of a rigorous assessment of some common causes of pseudoresistance, the burden of true resistant hypertension in the dialysis population remains unknown. What distinguishes apparent treatment-resistance from true resistance is white-coat hypertension and adherence to medications. Accordingly, the diagnostic workup of a dialysis patient with apparent treatment-resistant hypertension on dialysis includes the accurate determination of BP control status with the use of home or ambulatory BP monitoring and exclusion of nonadherence to the prescribed antihypertensive regimen. In a patient on dialysis with inadequately controlled BP, despite adherence to therapy with maximally tolerated doses of a β -blocker, a long-acting dihydropyridine calcium channel blocker, and a renin-angiotensin system inhibitor, volume-mediated hypertension is the most important treatable cause of resistance. In daily clinical practice, such patients are often managed with intensification of antihypertensive therapy. However, this therapeutic strategy is likely to fail if volume overload is not adequately recognized or treated. Instead of increasing the number of prescribed BP-lowering medications, we recommend diet and dialysate restricted in sodium to facilitate achievement of dry weight. The achievement of dry weight is facilitated by an adequate time on dialysis of at least 4 hours for delivering an adequate dialysis dose. In this article, we review the epidemiology, diagnosis, and management of resistant hypertension among patients on dialysis.
Impact of the COVID-19 Pandemic on Medical Expenditures Among Medicare Fee-for-Service Beneficiaries Aged ≥67 Years With Diabetes
Authors: Yu Wang, Ping Zhang, Xilin Zhou, Deborah Rolka, Giuseppina Imperatore
Journal: Diabetes Care (2024)

OBJECTIVE To compare total and out-of-pocket (OOP) medical expenditures between pre–COVID-19 (March 2019 to February 2020) and COVID-19 (March 2020 to February 2022) periods among Medicare beneficiaries with diabetes. RESEARCH DESIGN AND METHODS Data were from 100% Medicare fee-for-service claims. Diabetes was identified using ICD-10 codes. We calculated quarterly total and OOP medical expenditures at the population and per capita level in total and by service type. Per capita expenditures were calculated by dividing the population expenditure by the number of beneficiaries with diabetes in the same quarter. Changes in expenditures were calculated as the differences in the same quarters between the prepandemic and pandemic years. RESULTS Population total expenditure fell to $33.6 billion in the 1st quarter of the pandemic from $41.7 billion in the same prepandemic quarter; it then bounced back to $36.8 billion by the 4th quarter of the 2nd pandemic year. The per capita total expenditure fell to $5,356 in the 1st quarter of the pandemic from $6,500 in the same prepandemic quarter. It then increased to $6,096 by the 4th quarter of the 2nd pandemic year, surpassing the same quarter in the prepandemic year ($5,982). Both population and per capita OOP expenditures during the pandemic period were lower than the prepandemic period. Changes in per capita expenditure between the pre–COVID-19 and COVID-19 periods by service type varied. CONCLUSIONS COVID-19 had a significant impact on both total and per capita medical expenditures among Medicare beneficiaries with diabetes. The COVID-19 pandemic was associated with lower OOP expenditures.
<i>TREX1</i> Inactivation Unleashes Cancer Cell STING–Interferon Signaling and Promotes Antitumor Immunity
Authors: Tetsuo Tani, Haritha Mathsyaraja, Marco Campisi, Ze-Hua Li, Koji Haratani, Caroline G. Fahey, Keiichi Ota, Navin R. Mahadevan, Yingxiao Shi, Shin Saito, Kei Mizuno, Tran C. Thai, Nobunari Sasaki, Mizuki Homme, Choudhury Fabliha B. Yusuf, Adam Kashishian, Jipsa Panchal, Min Wang, Benjamin J. Wolf, Thanh U. Barbie, Cloud P. Paweletz, Prafulla C. Gokhale, David Liu, Ravindra Uppaluri, Shunsuke Kitajima, Jennifer Cain, David A. Barbie
Journal: Cancer Discovery (2024)

Abstract A substantial fraction of cancers evade immune detection by silencing Stimulator of Interferon Genes (STING)-Interferon (IFN) signaling. Therapeutic reactivation of this program via STING agonists, epigenetic, or DNA-damaging therapies can restore antitumor immunity in multiple preclinical models. Here we show that adaptive induction of three prime exonuclease 1 (TREX1) restrains STING-dependent nucleic acid sensing in cancer cells via its catalytic function in degrading cytosolic DNA. Cancer cell TREX1 expression is coordinately induced with STING by autocrine IFN and downstream STAT1, preventing signal amplification. TREX1 inactivation in cancer cells thus unleashes STING–IFN signaling, recruiting T and natural killer (NK) cells, sensitizing to NK cell–derived IFNγ, and cooperating with programmed cell death protein 1 blockade in multiple mouse tumor models to enhance immunogenicity. Targeting TREX1 may represent a complementary strategy to induce cytosolic DNA and amplify cancer cell STING–IFN signaling as a means to sensitize tumors to immune checkpoint blockade (ICB) and/or cell therapies. Significance: STING–IFN signaling in cancer cells promotes tumor cell immunogenicity. Inactivation of the DNA exonuclease TREX1, which is adaptively upregulated to limit pathway activation in cancer cells, recruits immune effector cells and primes NK cell–mediated killing. Targeting TREX1 has substantial therapeutic potential to amplify cancer cell immunogenicity and overcome ICB resistance. This article is featured in Selected Articles from This Issue, p. 695
Inflammatory recruitment of healthy hematopoietic stem and progenitor cells in the acute myeloid leukemia niche
Authors: Ding-Wen Chen, Jian-Meng Fan, Julie M. Schrey, Dana V. Mitchell, Seul K. Jung, Stephanie N. Hurwitz, Empar B. Perez, Mauro J. Muraro, Martin Carroll, Deanne M. Taylor, Peter Kurre
Journal: Leukemia (2024)

Abstract Inflammation in the bone marrow (BM) microenvironment is a constitutive component of leukemogenesis in acute myeloid leukemia (AML). Current evidence suggests that both leukemic blasts and stroma secrete proinflammatory factors that actively suppress the function of healthy hematopoietic stem and progenitor cells (HSPCs). HSPCs are also cellular components of the innate immune system, and we reasoned that they may actively propagate the inflammation in the leukemic niche. In two separate congenic models of AML we confirm by evaluation of the BM plasma secretome and HSPC-selective single-cell RNA sequencing (scRNA-Seq) that multipotent progenitors and long-lived stem cells adopt inflammatory gene expression programs, even at low leukemic infiltration of the BM. In particular, we observe interferon gamma (IFN-γ) pathway activation, along with secretion of its chemokine target, CXCL10. We show that AML-derived nanometer-sized extracellular vesicles (EV AML ) are sufficient to trigger this inflammatory HSPC response, both in vitro and in vivo. Altogether, our studies indicate that HSPCs are an unrecognized component of the inflammatory adaptation of the BM by leukemic cells. The pro-inflammatory conversion and long-lived presence of HSPCs in the BM along with their regenerative re-expansion during remission may impact clonal selection and disease evolution.
Appraisal of amyloidosis imaging practices in the Middle East/North Africa (PYP-MENA)
Authors: Firas Al Badarin, Masoud Garashi, Ahmed Aljizeeri, Ramzi Tabbalat, Adel Allam, Salah Eddine Bouyoucef, Ammar Chauhdary
Journal:  (2024)

Abstract Aims Whereas recommendations to optimize performance and yield of cardiac scintigraphy studies with bone-seeking tracers have been published, little is known about real-world adherence to these best practices, especially outside North America and Europe. Accordingly, we described imaging practices with this modality in a sample of nuclear laboratories in the Middle East/North Africa (MENA) region. Methods and results Laboratories performing radionuclide imaging for cardiac amyloidosis in the MENA region were invited to participate in this study to describe installed camera systems, type and dose of bone-avid tracers used, imaging protocols, and criteria used for study interpretation. Out of 19 invited sites, 10 completed the survey (70% government-run; 90% accredited), sites have been involved with amyloid imaging for a median of 49 months (interquartile range 24–60). The median injected dose was 20 mCi (range 10–25), and PYP was used by 90% of sites in this sample. Planar imaging with single photon emission computed tomography (SPECT) reconstruction was performed at all sites, including seven sites that performed SPECT/CT reconstruction. Lastly, only 50% of sites relied on evidence of myocardial uptake by SPECT to confirm the diagnosis of ATTR cardiomyopathy, while the rest relied on visual assessment and heart/contralateral ratio. Conclusion This study is the first to describe variation in imaging practices across sites in the MENA region, especially in acquisition protocols and interpretation standards. Eliminating heterogeneities identified by this study will harmonize image interpretation and reporting and will facilitate successful conduct of regional multi-centre studies.
Looking Beyond the Lower Airways for Microbes Affecting Pulmonary Fibrosis
Authors: Fares Darawshy, Philip L. Molyneaux, Leopoldo N. Segal
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Looking Beyond the Lower Airways for Microbes Affecting Pulmonary Fibrosis." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Response by Sayols-Baixeras et al to Letter Regarding Article, “ <i>Streptococcus</i> Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort”
Authors: Sergi Sayols-Baixeras, Koen F. Dekkers, Marju Orho-Melander, Tove Fall
Journal: Circulation (2024)
Coronary Artery Calcification: Current Concepts and Clinical Implications
Authors: Carlotta Onnis, Renu Virmani, Kenji Kawai, Valentina Nardi, Amir Lerman, Filippo Cademartiri, Roberta Scicolone, Alberto Boi, Terenzio Congiu, Gavino Faa, Peter Libby, Luca Saba
Journal: Circulation (2024)

Coronary artery calcification (CAC) accompanies the development of advanced atherosclerosis. Its role in atherosclerosis holds great interest because the presence and burden of coronary calcification provide direct evidence of the presence and extent of coronary artery disease; furthermore, CAC predicts future events independently of concomitant conventional cardiovascular risk factors and to a greater extent than any other noninvasive biomarker of this disease. Nevertheless, the relationship between CAC and the susceptibility of a plaque to provoke a thrombotic event remains incompletely understood. This review summarizes the current understanding and literature on CAC. It outlines the pathophysiology of CAC and reviews laboratory, histopathological, and genetic studies, as well as imaging findings, to characterize different types of calcification and to elucidate their implications. Some patterns of calcification such as microcalcification portend increased risk of rupture and cardiovascular events and may improve prognosis assessment noninvasively. However, contemporary computed tomography cannot assess early microcalcification. Limited spatial resolution and blooming artifacts may hinder estimation of degree of coronary artery stenosis. Technical advances such as photon counting detectors and combination with nuclear approaches (eg, NaF imaging) promise to improve the performance of cardiac computed tomography. These innovations may speed achieving the ultimate goal of providing noninvasively specific and clinically actionable information.
Pathogenic Variants of Scavenger Receptor <i>CD36</i> Lead to Decreased Efferocytosis and Predispose to Myocarditis Following Vaccination With Pfizer-BioNTech BNT162b2 Against Coronavirus Infection (COVID-19)
Authors: Christina Canavati, Ahmad Siam, Sapir Labes, Nirit Trabelsi, Eshcar Regev, Elchanan Parnasa, Barhoum Barhoum, Nur Magadle, Ofer Perzon, Maya Braun, Hagar Mor-Shaked, Ora Schueler-Furman, Yuval Tabach, Dror Mevorach
Journal: Circulation (2024)
High-Sensitivity Cardiac Troponin I for Long-Term Cardiovascular Risk Stratification in a Cancer Clinic Population
Authors: Peter A Kavsak, Joshua O Cerasuolo, David Kirkwood, Richard Perez, Hsien Seow, Jinhui Ma, Andrew Worster, Dennis T Ko, Sukhbinder Dhesy-Thind, Darryl Leong
Journal: JACC CardioOncology (2024)
Clinical Outcomes Among Immunotherapy-Treated Patients With Primary Cardiac Soft Tissue Sarcomas
Authors: Amin H. Nassar, Edward El-Am, Ryan Denu, Sarah Abou Alaiwi, Talal El Zarif, Walid Macaron, Noha Abdel-Wahab, Aakash Desai, Caleb Smith, Kaushal Parikh, Muhannad Abbasi, Elias Bou Farhat, James M. Williams, Jeremy D. Collins, Ahmad Al-Hader, Rana R. McKay, Carmel Malvar, Mohamad Sabra, Caiwei Zhong, Raquelle El Alam, Omar Chehab, Joao Lima, Minh Phan, Hanna Ferreira Dalla Pria, Alexandra Trevino, Tomas G. Neilan, Jennifer M. Kwan, Vinod Ravi, Hari Deshpande, George Demetri, Toni K. Choueiri, Abdul Rafeh Naqash
Journal: JACC CardioOncology (2024)

Primary cardiac soft tissue sarcomas (CSTS) affect young adults, with dismal outcomes. The aim of this study was to investigate the clinical outcomes of patients with CSTS receiving immune checkpoint inhibitors (ICIs). A retrospective, multi-institutional cohort study was conducted among patients with CSTS between 2015 and 2022. The patients were treated with ICI-based regimens. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates were determined according to Response Evaluation Criteria in Solid Tumors version 1.1. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events version 5.0. Among 24 patients with CSTS, 17 (70.8%) were White, and 13 (54.2%) were male. Eight patients (33.3%) had angiosarcoma. At the time of ICI treatment, 18 patients (75.0%) had metastatic CSTS, and 4 (16.7%) had locally advanced disease. ICIs were administered as the first-line therapy in 6 patients (25.0%) and as the second-line therapy or beyond in 18 patients (75.0%). For the 18 patients with available response data, objective response rate was 11.1% (n = 2 of 18). The median PFS and median OS in advanced and metastatic CSTS (n = 22) were 5.7 months (95% CI: 2.8-13.3 months) and 14.9 months (95% CI: 5.7-23.7 months), respectively. The median PFS and OS were significantly shorter in patients with cardiac angiosarcomas than in those with nonangiosarcoma CSTS: median PFS was 1.7 vs 11 months, respectively (P < 0.0001), and median OS was 3.0 vs 24.0 months, respectively (P = 0.008). Any grade treatment-related adverse events occurred exclusively in the 15 patients with nonangiosarcoma CSTS (n = 7 [46.7%]), of which 6 (40.0%) were grade ≥3. Although ICIs demonstrate modest activity in CSTS, durable benefit was observed in a subset of patients with nonangiosarcoma, albeit with higher toxicity.
Impact of the ESC Cardio-Oncology Guidelines Biomarker Criteria on Incidence of Cancer Therapy–Related Cardiac Dysfunction
Authors: Albulena Mecinaj, Geeta Gulati, Anne Hansen Ree, Berit Gravdehaug, Helge Røsjø, Kjetil Steine, Torbjørn Wisløff, Jürgen Geisler, Torbjørn Omland, Siri Lagethon Heck
Journal: JACC CardioOncology (2024)

The impact of recent consensus definitions of cancer therapy-related cardiac dysfunction (CTRCD) from the European Society of Cardiology cardio-oncology guidelines on the reported incidence of CTRCD has not yet been assessed.
Use of extracorporeal shockwave therapies for athletes and physically active individuals: a systematic review
Authors: Hye Chang Rhim, Jaehyung Shin, Jane Kang, Paige Dyrek, Zack Crockett, Pearl Galido, Carrie Wade, Karsten Hollander, Joanne Borg-Stein, Steven Sampson, Adam S Tenforde
Journal: British Journal of Sports Medicine (2024)

Objective To determine the efficacy of extracorporeal shockwave therapy (ESWT) and investigate outcomes following the use of ESWT for athletes and physically active individuals. Design Systematic review. Data sources We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and searched four databases: PubMed (NLM), Embase (Elsevier), CINAHL Complete (EBSCO) and Web of Science (Clarivate). Eligibility criteria for selecting studies Included studies were randomised controlled trials, cohort and case–control studies, cases series and reports that evaluated outcomes following ESWT for athletes, physically active individuals and occupational groups requiring regular physical activity such as military cadets. Results 56 studies with 1874 athletes or physically active individuals were included. Using the Oxford level of evidence rating, included studies were 18 level I (32.1%), 3 level II (5.4%), 10 level III (17.9%), 13 level IV (23.2%) and 12 level V (21.4%). Based on the level I studies, ESWT may be effective alone in plantar fasciitis, lateral epicondylitis and proximal hamstring tendinopathy and as an adjunct to exercise treatment in medial tibial stress syndrome and osteitis pubis in athletes or physically active individuals. In most studies, athletes were allowed to continue activities and training and tolerated ESWT with minimal side effects. Conclusion ESWT may offer an efficacious treatment alone or as an adjunct to concurrent exercise therapy in selected sports-related injuries and without major adverse events. Further high-level research is needed to better define the role and clinical outcomes of ESWT.
Abstract 14594: Dual Contrast-Enhanced Micro-Computed Tomography for Simultaneous Characterization of Macrocalcification and Tri-Layered Structural Remodeling in Explanted Human Aortic Valves
Authors: Mustapha El Zeini, Angela Kabiri, Arturas Vailionis, John Perrino, Kristin C Jensen, Thomas A Burdon, Yasuhiro Shudo, Jack Boyd, Y Joe Woo, Lydia Marie-Joubert, Ian Y Chen
Journal: Circulation (2023)

Background: Micro-computed tomography (microCT) is excellent for detecting macrocalcification but ineffective at revealing other pathologically relevant structural details in the valves affected by aortic stenosis (AS). Here, we aimed to develop a dual contrast-enhanced microCT technique to simultaneously assess macrocalcification and layer-specific remodeling in diseased human aortic valves. Methods: Diseased (n=15) and normal (n=9) aortic valve leaflets were obtained from human subjects undergoing aortic valve replacement for AS and heart transplantation/autopsy, respectively. Leaflets were fixed (4% paraformaldehyde and 2% glutaraldehyde), stained with dual contrast (1% osmium tetroxide and 1% uranyl acetate), and embedded in epoxy resin. Additional unstained leaflets (n=3 diseased, n=3 normal), similarly processed otherwise, served as staining controls. MicroCT of embedded leaflets was performed using a ZEISS Xradia 520 Versa scanner, with low energy beam (80 kVp, 5 W, LE4 filter) and high-resolution acquisitions (15 μm x 15 μm, 5 sec exposure x 1601 projections). Reconstructed images were analyzed for leaflet/layer thicknesses at midline and macrocalcification volume using Dragonfly. Results: The tri-layered tissue structure was only visualized in stained but not unstained leaflets ( p =0.002). With staining, each layer was found to be thicker in the diseased than the normal leaflets (0.28±0.13 mm vs 0.18±0.07 mm, p =0.0002 for fibrosa; 0.64±0.68 mm vs 0.29±0.19 mm, p =0.012 for spongiosa; 0.32±0.16 mm vs 0.16±0.07 mm, p &lt;0.0001 for ventricularis). The macrocalcification volume in the diseased leaflets was greater than that in the normal leaflets (84.7±84.4 mm 3 vs 0 mm 3 , p &lt;0.0001) and correlated only with the thickness of spongiosa ( r =0.79, p &lt;0.001) but not other layers ( p =0.67, p =0.26). Macrocalcification was as frequently observed in spongiosa as in fibrosa (66.7% vs 66.7% of diseased leaflets, p =0.3) but never in ventricularis. Conclusions: Dual contrast-enhanced microCT enables high-quality imaging of both macrocalcification and layer-specific remodeling in diseased human aortic valves. The results here suggest an intimate relationship between macrocalcification and spongiosa that warrants further investigation.
Correction: hsa_circ_0007919 induces LIG1 transcription by binding to FOXA1/TET1 to enhance the DNA damage response and promote gemcitabine resistance in pancreatic ductal adenocarcinoma
Authors: Lei Xu, Xiao Ma, Xiuzhong Zhang, Chong Zhang, Yi Zhang, Shuai Gong, Nai Wu, Peng Zhang, Xinyu Feng, Jiaxuan Guo, Mengmeng Zhao, Zeqiang Ren, Pengbo Zhang
Journal: Molecular Cancer (2024)
Reply to ‘Cognitive criteria in HIV: greater consensus is needed’
Authors: Sam Nightingale, Paola Cinque, Ameet Dravid, Anna J. Dreyer, Magnus Gisslén, John A. Joska, Judith Kwasa, Ana-Claire Meyer, Nombeko Mpongo, Noeline Nakasujja, Roger Pebody, Anton Pozniak, Richard W. Price, Deanna Saylor, Kevin G. F. Thomas, Jonathan Underwood, Jaime H. Vera, Alan Winston
Journal: Nature Reviews Neurology (2024)