tbuckley/cabot-search huggingface dataset:
Abstract 11912: Temporal Trends in the Incidence of Non-Shockable In-Hospital Cardiac Arrest in Septic Patients
Authors: Arham Pasha, Muddasir Ashraf, Arshad Jahangir
Journal: Circulation (2023)

Background: Owing to increased awareness of the timely recognition and treatment of sepsis in the USA, sepsis care has improved over time with better outcomes. Hypothesis: We hypothesized that the incidence of non-shockable in-hospital cardiac arrest (IHCA) has also improved over time with improving sepsis care. Aims: The primary objective was to evaluate temporal trends of non-shockable IHCA in septic patients. The secondary objective was to evaluate these trends stratified by age, sex, and race. Methods: Using the National Inpatient Sample, we studied all adult patients hospitalized with sepsis from 2005 to 2019. We used multivariate logistic regression for trend analysis. Results: Of 26 million adult patients admitted with sepsis from 2005 to 2019 in the USA, with a mean age of 66 ±0.043 years, 50% were females. The mean age decreased from 68 years in 2005 to 65 years in 2019. The risk-adjusted rates of non-shockable IHCA in septic patients decreased from 2.4% in 2005 to 1.1% in 2019 (Figure 1, Panel A) after accounting for differences in age, sex, and comorbidity burden. The risk-adjusted rates were highest in the age group 45-64 and lowest in the oldest age group ≥85 years (Panel B). Furthermore, the sex-stratified analysis showed consistently higher rates of non-shockable IHCA in males than in females throughout our study (Panel C). Finally, the risk-adjusted rates of non-shockable IHCA were consistently highest in Black patients compared to other races throughout our study period (Panel D). Conclusions: The incidence of non-shockable IHCA in septic patients has significantly improved with increased awareness and improved care of sepsis. Initiatives like Surviving Sepsis Campaign need continued implementation in hospitals, with constant monitoring of compliance with these guidelines to further improve the incidence of non-shockable IHCA in septic patients.
Abstract 11373: Suppression of Plasma Angiotensin II by GLP-1 in Humans is Independent of Changes in Plasma Angiotensinogen
Authors: Boye L Jensen, Ali Asmar
Journal: Circulation (2023)

Introduction: In humans, the natriuretic effect of GLP-1 depends on GLP-1 receptor interaction, is independent of changes in renal blood flow, renin, ANP, and aldosterone but is accompanied by suppression of angiotensin II (ANGII). The mechanism by which GLP-1 reduces ANGII independently of changes in renin is not clarified. Hypothesis: It was hypothesized that GLP-1 suppresses renin substrate, angiotensinogen, in plasma. Methods: To test this proposal, we measured arterial angiotensinogen concentration in biobanked plasma samples from healthy males during a 3-hour GLP-1 infusion that induced natriuresis (1). Samples were from a study with fixed sodium intake where eight healthy men were examined twice in random order during a 3-hour infusion of either GLP-1(1.5 pmol kg -1 min -1 ) or vehicle together with an intravenous infusion of 0.9% NaCl (750 mL/hour). Arterial plasma angiotensinogen was measured in plasma by dilution (1:200) and addition of excess exogenous human renin (Inst. Of Biological Standards UK). After prolonged incubation, ANGI was quantified by radioimmunoassay. Intraassay variation was 9-12%. Results: Arterial plasma angiotensinogen and renin levels decreased similarly and modestly (~15 and ~30%, respectively) after NaCl infusion during both studies whereas ANGII levels decreased significantly (~25%) only during GLP-1 infusion. Conclusions: Suppression of plasma angiotensinogen is less likely to account for GLP-1-mediated ANGII suppression in healthy young males. In perspective, GLP-1 could enhance pathways of ANGII degradation rather than inhibit its formation. 1. Asmar A et al. Extracellular fluid volume expansion uncovers a natriuretic action of GLP-1: a functional GLP-1-renal axis in man. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2509-2519.
Development of LAG-3/FGL1 blocking peptide and combination with radiotherapy for cancer immunotherapy
Authors: Yuzhen Qian, Yixuan Sun, Peishang Shi, Xiuman Zhou, Qiongqiong Zhang, Qingyu Dong, Shengzhe Jin, Lu Qiu, Xiaoshuang Niu, Xiaowen Zhou, Wenshan Zhao, Yahong Wu, Wenjie Zhai, Yanfeng Gao
Journal: Acta Pharmaceutica Sinica B (2023)

Aside from antibodies, peptides show great potential as immune checkpoint inhibitors (ICIs) due to several advantages, such as better tumor penetration and lower cost. Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Here, we found that LAG-3 expression was higher than programmed cell death protein 1 (PD-1) in multiple human cancers by TCGA databases, and successfully identified a LAG-3 binding peptide LFP-6 by phage display bio-panning, which specifically blocks the interaction of LAG-3/FGL1 but not LAG-3/MHC-II. Subsequently, d-amino acids were introduced to substitute the N- and C-terminus of LFP-6 to obtain the proteolysis-resistant peptide LFP-D1, which restores T cell function
High and intermediate risk pulmonary embolism in the ICU
Authors: Scott J. Millington, Nadia Aissaoui, Emma Bowcock, Daniel Brodie, Karine E. A. Burns, Ghislaine Douflé, François Haddad, Tim Lahm, Gregory Piazza, Olivier Sanchez, Laurent Savale, Antoine Vieillard-Baron
Journal: Intensive Care Medicine (2023)
Deucravacitinib, a selective, allosteric tyrosine kinase 2 inhibitor, in scalp psoriasis: A subset analysis of two phase 3 randomized trials in plaque psoriasis
Authors: Andrew Blauvelt, Phoebe Rich, Howard Sofen, Bruce Strober, Joseph F. Merola, Mark Lebwohl, Akimichi Morita, Jacek C. Szepietowski, Jo Lambert, Lauren Hippeli, Elizabeth Colston, Eugene Balagula, Subhashis Banerjee, Diamant Thaçi
Journal: Journal of the American Academy of Dermatology (2023)

BackgroundScalp involvement in plaque psoriasis is challenging to treat.ObjectiveTo evaluate the efficacy and safety of deucravacitinib (DEUC) in scalp psoriasis.MethodsPOETYK PSO-1 and PSO-2 were global phase 3, 52-week, double-blinded trials in adults with moderate to severe psoriasis. Patients were randomized 1:2:1 to oral placebo, DEUC 6 mg once daily, or apremilast 30 mg twice daily. This pooled secondary analysis evaluated scalp-specific Physician Global Assessment score of 0 or 1 (0/1), ≥90% improvement from baseline in Psoriasis Scalp Severity Index, and change from baseline in Psoriasis Scalp Severity Index. Adverse events were evaluated through week 16.ResultsOverall, 1084 patients with moderate to severe scalp psoriasis at baseline were included. At week 16, response rates were greater with DEUC versus placebo or apremilast for scalp-specific Physician Global Assessment 0/1 (64.0% vs 17.3% vs 37.7%; P < .0001), ≥90% improvement from baseline in Psoriasis Scalp Severity Index (50.6% vs 10.5% vs 26.1%; P < .0001), and change from baseline in Psoriasis Scalp Severity Index. Responses were maintained through 52 weeks with continuous DEUC. Safety was consistent with the entire study population.LimitationsLack of data in milder scalp psoriasis.ConclusionDEUC was significantly more efficacious than placebo or apremilast in improving moderate to severe scalp psoriasis and was well tolerated.
Loss of mitochondrial adaptation associates with deterioration of mitochondrial turnover and structure in metabolic dysfunction-associated steatotic liver disease
Authors: Theresia Sarabhai, Sabine Kahl, Sofiya Gancheva, Lucia Mastrototaro, Bedair Dewidar, Dominik Pesta, Jacqueline M. Ratter-Rieck, Pavel Bobrov, Kay Jeruschke, Irene Esposito, Matthias Schlensak, Michael Roden
Journal: Metabolism (2023)
Tailoring allocation policies and improving access to paediatric liver transplantation over a 16-year period
Authors: Marco Spada, Roberta Angelico, Silvia Trapani, Lucia Masiero, Francesca Puoti, Michele Colledan, Davide Cintorino, Renato Romagnoli, Umberto Cillo, Massimo Cardillo
Journal: Journal of Hepatology (2023)
Untargeted serum metabolomics reveals novel metabolite associations and disruptions in amino acid and lipid metabolism in Parkinson’s disease
Authors: Kimberly C. Paul, Keren Zhang, Douglas I. Walker, Janet Sinsheimer, Yu Yu, Cynthia Kusters, Irish Del Rosario, Aline Duarte Folle, Adrienne M. Keener, Jeff Bronstein, Dean P. Jones, Beate Ritz
Journal: Molecular Neurodegeneration (2023)

Abstract Background Untargeted high-resolution metabolomic profiling provides simultaneous measurement of thousands of metabolites. Metabolic networks based on these data can help uncover disease-related perturbations across interconnected pathways. Objective Identify metabolic disturbances associated with Parkinson’s disease (PD) in two population-based studies using untargeted metabolomics. Methods We performed a metabolome-wide association study (MWAS) of PD using serum-based untargeted metabolomics data derived from liquid chromatography with high-resolution mass spectrometry (LC-HRMS) using two distinct population-based case-control populations. We also combined our results with a previous publication of 34 metabolites linked to PD in a large-scale, untargeted MWAS to assess external validation. Results LC-HRMS detected 4,762 metabolites for analysis (HILIC: 2716 metabolites; C18: 2046 metabolites). We identified 296 features associated with PD at FDR&lt;0.05, 134 having a log 2 fold change (FC) beyond ±0.5 (228 beyond ±0.25). Of these, 104 were independently associated with PD in both discovery and replication studies at p &lt;0.05 (170 at p &lt;0.10), while 27 were associated with levodopa-equivalent dose among the PD patients. Intriguingly, among the externally validated features were the microbial-related metabolites, p-cresol glucuronide (FC=2.52, 95% CI=1.67, 3.81, FDR=7.8e-04) and p-cresol sulfate. P-cresol glucuronide was also associated with motor symptoms among patients. Additional externally validated metabolites associated with PD include phenylacetyl-L-glutamine, trigonelline, kynurenine, biliverdin, and pantothenic acid. Novel associations include the anti-inflammatory metabolite itaconate (FC=0.79, 95% CI=0.73, 0.86; FDR=2.17E-06) and cysteine-S-sulfate (FC=1.56, 95% CI=1.39, 1.75; FDR=3.43E-11). Seventeen pathways were enriched, including several related to amino acid and lipid metabolism. Conclusions Our results revealed PD-associated metabolites, confirming several previous observations, including for p-cresol glucuronide, and newly implicating interesting metabolites, such as itaconate. Our data also suggests metabolic disturbances in amino acid and lipid metabolism and inflammatory processes in PD.
Time in Tight Glucose Range in Type 1 Diabetes: Predictive Factors and Achievable Targets in Real-World Users of the MiniMed 780G System
Authors: Javier Castañeda, Arcelia Arrieta, Tim van den Heuvel, Tadej Battelino, Ohad Cohen
Journal: Diabetes Care (2023)

We studied time in tight range (TITR) (70-140 mg/dL) in real-world users of the MiniMed 780G system (MM780G).
Spatially Resolved Tumor Microenvironment Predicts Treatment Outcomes in Relapsed/Refractory Hodgkin Lymphoma
Authors: Tomohiro Aoki, Aixiang Jiang, Alexander Xu, Yifan Yin, Alicia Gamboa, Katy Milne, Katsuyoshi Takata, Tomoko Miyata-Takata, Shanee Chung, Shinya Rai, Shaocheng Wu, Mary Warren, Celia Strong, Talia Goodyear, Kayleigh Morris, Lauren C. Chong, Monirath Hav, Anthony R. Colombo, Adele Telenius, Merrill Boyle, Susana Ben-Neriah, Maryse Power, Alina S. Gerrie, Andrew P. Weng, Aly Karsan, Andrew Roth, Pedro Farinha, David W. Scott, Kerry J. Savage, Brad H. Nelson, Akil Merchant, Christian Steidl
Journal: Journal of Clinical Oncology (2023)

About a third of patients with relapsed or refractory classic Hodgkin lymphoma (r/r CHL) succumb to their disease after high-dose chemotherapy followed by autologous stem-cell transplantation (HDC/ASCT). Here, we aimed to describe spatially resolved tumor microenvironment (TME) ecosystems to establish novel biomarkers associated with treatment failure in r/r CHL.
Pulmonary Fibrosis Stakeholder Summit: A Joint NHLBI, Three Lakes Foundation, and Pulmonary Fibrosis Foundation Workshop Report
Authors: Sydney B. Montesi, Christian R. Gomez, Michael Beers, Robert Brown, Ishanu Chattopadhyay, Kevin R. Flaherty, Christine Kim Garcia, Brigitte Gomperts, Lida P. Hariri, Cory M. Hogaboam, R. Gisli Jenkins, Naftali Kaminski, Grace Hyun J. Kim, Melanie Königshoff, Martin Kolb, Darrell N. Kotton, Jonathan A. Kropski, Joseph Lasky, Chelsea M. Magin, Toby M. Maher, Mark McCormick, Bethany B. Moore, Cheryl Nickerson-Nutter, Justin Oldham, Anna J. Podolanczuk, Ganesh Raghu, Ivan Rosas, Steven M. Rowe, William T. Schmidt, David Schwartz, Jessica E. Shore, Cathie Spino, J. Matthew Craig, Fernando J. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Despite progress in elucidation of disease mechanisms, identification of risk factors, biomarker discovery, and the approval of two medications to slow lung function decline in idiopathic pulmonary fibrosis and one medication to slow lung function decline in progressive pulmonary fibrosis, pulmonary fibrosis remains a disease with a high morbidity and mortality. In recognition of the need to catalyze ongoing advances and collaboration in field of pulmonary fibrosis, the National Heart, Lung, and Blood Institute, Three Lakes Foundation, and Pulmonary Fibrosis Foundation hosted the Pulmonary Fibrosis Stakeholder Summit on November 8-9, 2022. This workshop was held virtually and organized into three topic areas: 1) novel models and research tools to better study pulmonary fibrosis and uncover new therapies, 2) early disease risk factors and methods to improve diagnosis, and 3) innovative approaches towards clinical trial design for pulmonary fibrosis. In this workshop report, we summarize the content of the presentations and discussions, enumerating research opportunities for advancing our understanding of pathogenesis, treatment, and outcomes of pulmonary fibrosis.
Five principles for the development of minimally disruptive digital medicine
Authors: Tiphaine Lenfant, Philippe Ravaud, Victor M. Montori, Gro R. Berntsen, Viet-Thi Tran
Journal: BMJ (2023)

Experts predict that no society or healthcare system will be able to sustainably care for patients with chronic conditions in the next 20 years. 1 Similarly, healthcare is increasingly unsustainable for patients, overwhelmed by the work of accessing and using healthcare services and enacting self-care routines.
Abstract 12278: A Case of Hereditary Transthyretin Amyloidosis Caused by a Rare Mutation
Authors: Leah Stinson, Spencer Carter, Jill Waldron, Josef Stehlik, Amandeep Godara, Konstantinos Sideris, Lina Brinker, Ryan Mooney
Journal: Circulation (2023)

Introduction: Transthyretin amyloidosis (ATTR) is an underdiagnosed multisystem disease caused by dissociation of the tetrameric structure, misfolding, and deposition of the protein transthyretin. More than 100 known mutations that decrease the stability of transthyretin have been implicated in hereditary ATTR (ATTRv). Organ tropism and disease progression can vary significantly depending on the specific mutation, though cardiomyopathy and neuropathy are the most common phenotypes (Figure 1b). Reproducibly tracking the pattern of end organ dysfunction in ATTRv caused by novel mutations may help elucidate the mechanism of mutation-specific organ tropism and predict the potential disease course for patients with the same mutation. Case: The index patient is an 86-year-old male with a history of atrial fibrillation, tachy-brady syndrome requiring a pacemaker, orthostatic hypotension, peripheral neuropathy, and left ventricular hypertrophy (interventricular septum 1.4 cm prior to diagnosis) on echocardiogram. The constellation of symptoms raised the clinical suspicion for amyloidosis which was confirmed on endomyocardial biopsy. Given his age, he was presumed to have wild type ATTR by the local team. Upon referral to our center, genetic testing was performed which revealed the missense mutation c.229G&gt;A which results in the amino acid substitution p.Gly77Arg, and has previously only been reported in one patient in Sweden. We initiated family screening and identified multiple family members with the mutation with varying phenotypes including no symptoms, cardiomyopathy, and neuropathy (figure 1a). Discussion: We identified a family with a rare c.229G&gt;A mutation, and report on a mixed cardiomyopathy and neuropathy phenotype. Our report highlights the importance of screening for pathologic genetic variants in all patients with a diagnosis of ATTR given the treatment and prognostic implications for patients and their family members.
Abstract 13587: Hemoglobin Levels Can Predict Early Rehospitalization in Advanced Heart Failure Patients Listed for Heart Transplantation Without Inotropes or Mechanical Circulatory Support
Authors: Tomoyasu Suenaga, Takeo Fujino, Yusuke Ishikawa, Keisuke Shinohara, Toru Hashimoto, Shouji Matsushima, Tomomi Ide, Miho Yagita, Hitoshi Komman, Masayo Toyosawa, Hiroyuki Tsutsui, Akira Shiose, Shintaro Kinugawa
Journal: Circulation (2023)

Background: Anemia is a common comorbidity which often coexists in patients with heart failure (HF), and is associated with poor clinical outcome. However, it is unclear whether hemoglobin value has clinical impact in advanced HF patients. Hypothesis: Hemoglobin value influence the clinical outcome of patients with advanced HF. Methods: We retrospectively reviewed clinical data of ambulatory advanced HF patients who were listed for heart transplantation at our institute without intravenous inotropes or mechanical circulatory support (MCS) between 2011 and 2022. We divided the patients with a hemoglobin of lower or higher than the median value, and compared a composite of all-cause death and rehospitalization for HF within 1 year. Results: We enrolled consecutive 38 HF patients (28 males, 49±11 years old). All patients had New York Heart Association III or IV symptoms. The median hemoglobin value at the time of listing for heart transplantation was 12.9 g/dL, 42% met the criteria of anemia, and 67% had iron deficiency. Patients in the lower hemoglobin group were characterized by lower body mass index (19.7±3.0 vs. 21.7±3.1 kg/m 2 , P=0.049), lower systolic blood pressure (84.0±7.6 vs. 88.9±6.2 mmHg, P=0.034) and lower albumin (4.0±0.4 vs. 4.3±0.3 g/dL, P=0.031) than those in the higher hemoglobin group. Age, prevalence of male, left ventricular ejection fraction and brain natriuretic peptide were comparable between the two groups. No patient died in either group at 1 year. The HF rehospitalization-free survival rate was significantly lower in the lower hemoglobin group (41% vs. 82% at 1 year, P=0.020). By multivariate Cox regression analyses, hemoglobin as a continuous variable was an independent predictor for early HF rehospitalization (odds ratio 0.70, 95% confidence interval 0.49-0.97, P=0.030). Conclusion: Lower hemoglobin was a predictor of early HF rehospitalization in ambulatory advanced HF patients listed for heart transplantation without inotropes or MCS.
Abstract 14605: Association of SGLT-2 Inhibition With Size of Myocardial Infarction in Patients With Type 2 Diabetes Mellitus
Authors: Istvan Bojti, Felicitas Bojti, Tau Hartikainen, Philipp Breitbart, Christian Valina, Nikolaus Löffelhardt, Klaus Kaier, Dennis Wolf, Dirk Westermann, Christoph B Olivier
Journal: Circulation (2023)

Introduction: Preclinical data suggest that sodium-glucose-cotransporter-2 inhibitors (SGLT-2i) reduce the size of myocardial infarction (MI). This study aimed to assess the association of SGLT-2i use with the size of MI and clinical outcome. Methods: In a retrospective single center cohort study, patients with diagnosed diabetes mellitus type 2 who were admitted for MI and treated with PCI between November 2015 and November 2022 were analyzed and grouped according to SGLT-2i use. Following PCI, serial high sensitivity troponin T (cTn, Roche) measurements were performed according to in-house protocol. The primary outcome was the size of MI determined by the peak cTn normalized on the endangered myocardial area (EMA) calculated according to culprit lesion localization and coronary arterial dominance. Secondary outcomes were in-hospital adverse events (i.e. in-hospital death or stroke) and length of intensive care unit (ICU) treatment. The propensity score method was used to assess the association with outcomes. Results: 631 patients were identified: 85 with ongoing SGLT-2i therapy and 537 with other antidiabetic medication. Patients using SGLT-2i were younger (median age [years]: 67 [interquartile range, IQR 59-73] vs. 73 [64-79], p&lt;0.01) and had a higher eGFR at admission (75 [57-91] vs. 68 [49-88] ml/min/1.73m 2 , p=0.03). The median cTn samples per patient was 6 (5-8). There was no significant difference in the peak cTn levels between the two groups (SGLT-2i use vs. no SGLT-2i use: 53 (12-173) vs. 65 (20-174) х the upper limit of normal [ULN], p=0.26). After augmented inverse-probability weighted propensity score matching, ongoing SGLT-2i therapy was significantly associated with a reduced MI size (difference between means: -2.19 [95% confidence interval, -4.07 to -0.31] x ULN/EMA (1/%), p=0.02). SGLT-2i use was associated with less in-hospital adverse events (-4.69 [-8.70 to -0.69] %, p=0.02) and with less days on ICU (-0.27 [-0.53 to -0.01] days, p=0.045). Conclusion: In this retrospective cohort study of patients with DM presenting with MI, prior prescription of SGLT-2i was associated with reduced MI size and fewer adverse events during hospitalization. This might indicate that SGLT2i reduces the size of MI.
Abstract 13567: Comparison of Change in Lipoprotein(a) Mass and Molar Concentrations by Alirocumab and Risk of Subsequent Cardiovascular Events in ODYSSEY OUTCOMES
Authors: Michael Szarek, Esther Reijnders, Philippe G Steg, J W Jukema, Markus Schwertfeger, Deepak Bhatt, Vera A Bittner, Rafael Diaz, Sergio fazio, Genevieve Garon, Shaun G Goodman, Robert A Harrington, Harvey D White, Andreas M Zeiher, Christa Cobbaert, Gregory G Schwartz
Journal: Circulation (2023)

Background: Baseline (BL) lipoprotein(a) (Lp(a)) concentration is similarly related to cardiovascular (CV) risk when measured in either mass or molar units by immunoassay (IA). Because of Lp(a) isoform variation in mass, differences may exist between Lp(a) measurement methods in terms of relating change to risk reduction. We determined whether the reduction in major adverse cardiovascular events (MACE) by PCSK9 inhibitor alirocumab (ALI) had a similar relationship to the reduction in Lp(a) concentration as measured by 3 different methods. Methods: Lp(a) was measured by IA-mass (Siemens), IA-molar (Roche), and mass spectrometry (MS)-molar assays at BL and month 4 (M4) in a subgroup of patients in the ODYSSEY OUTCOMES trial which compared PCSK9 inhibitor ALI with placebo in patients with recent acute coronary syndrome. Changes in Lp(a) from BL to M4 were related to subsequent risk of MACE (coronary heart disease (CHD) death, nonfatal myocardial infarction (NFMI), fatal + nonfatal ischemic stroke, or unstable angina hospitalization) in the ALI group. Proportional hazards models were adjusted for BL Lp(a), BL LDL-C and its change from BL to M4, and other patient characteristics. Hazard ratios (HR) were calculated for the median change of each Lp(a) assay. All analyses were by intention-to-treat. Results: Among 5500 patients randomized to ALI with available data from all 3 Lp(a) assays, 443 experienced a subsequent MACE. Changes in Lp(a) IA-mass and MS-molar concentration were significantly related to reduced MACE risk, while change in IA-molar concentration was marginally significant; associations were more evident with CHD death + NFMI ( Figure ). MACE HRs for median change were similar across tests. Conclusion: With caveats of a modest number of MACE for analysis, moderately elevated Lp(a) levels, and intra-patient variability in serial values, 3 Lp(a) assay methods appeared similarly predictive of ALI MACE reduction.