tbuckley/cabot-search huggingface dataset:
Development of a Follow-Up Measure to Ensure Complete Screening for Colorectal Cancer
Authors: Elizabeth L. Ciemins, Jeff T. Mohl, Carlos A. Moreno, Francis Colangelo, Robert A. Smith, Mary Barton
Journal: JAMA Network Open (2024)

Importance The current quality performance measure for colorectal cancer (CRC) screening is limited to initial screening. Despite low rates, there is no measure for appropriate follow-up with colonoscopy after receipt of an abnormal result of a stool-based screening test (SBT) for CRC. A quality performance measure is needed. Objective To develop and test a quality performance measure for follow-up colonoscopy within 6 months of an abnormal result of an SBT for CRC. Design, Setting, and Participants This retrospective quality improvement study examined data from January 1, 2016, to December 31, 2020, with 2018 plus 6 months of follow-up as the primary measurement period to verify performance rates, specify a potential measure, and test for validity, reliability, and feasibility. The Optum Labs Data Warehouse (OLDW), a deidentified database of health care claims and clinical data, was accessed. The OLDW contains longitudinal health information on enrollees and patients, representing a diverse mixture of ages and geographic regions across the US. For the database study, adults from 38 health care organizations (HCOs) aged 50 to 75 years who completed an initial CRC SBT with an abnormal result were observed to determine follow-up colonoscopy rates within 6 months. Rates were stratified by race, ethnicity, sex, insurance, and test modality. Three HCOs participated in the feasibility field testing. Data were analyzed from June 1, 2022, to May 31, 2023. Main Outcome and Measures The primary outcome consisted of follow-up colonoscopy rates following an abnormal SBT result for CRC. Reliability statistics were also calculated across HCOs, race, ethnicity, and measurement year. Results Among 20 581 adults (48.6% men and 51.4% women; 307 [1.5%] Asian, 492 [7.2%] Black, 644 [3.1%] Hispanic, and 17 705 [86.0%] White; mean [SD] age, 63.6 [7.1] years) in 38 health systems, 47.9% had a follow-up colonoscopy following an abnormal SBT result for CRC within 6 months. There was significant variation between HCOs. Notably, significantly fewer Black patients (37.1% [95% CI, 34.6%-39.5%]) and patients with Medicare (49.2% [95% CI, 47.7%-50.6%]) or Medicaid (39.2% [95% CI, 36.3%-42.1%]) insurance received a follow-up colonoscopy. A quality performance measure that tracks rates of follow-up within 6 months of an abnormal SBT result was observed to be feasible, valid, and reliable, with a median reliability statistic between HCOs of 94.5% (range, 74.3%-99.7%). Conclusions and Relevance The findings of this observational study of 20 581 adults suggest that a measure of follow-up colonoscopy within defined periods after an abnormal result of an SBT test for CRC is warranted based on low current performance rates and would be feasible to collect by health systems and produce valid, reliable results.
Artificial Intelligence Simulation of Adolescents’ Responses to Vaping-Prevention Messages
Authors: Paschal Sheeran, Alexander Kenny, Andrea Bermudez, Kurt Gray, Emily F. Galper, Marcella Boynton, Seth M. Noar
Journal: JAMA Pediatrics (2024)

This quality improvement study investigates if a large language model could simulate adolescents’ responses to vaping-prevention campaigns and identify the most effective messages to address the public health crisis of adolescent vaping.
Does Industry Really Develop Less Medicine With Clinical Benefit?—Reply
Authors: Leeza Osipenko
Journal: JAMA Internal Medicine (2024)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 2024 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 Internal Medicine journal
Visual Pathway Outcomes Based on Sample Size in Clinical Neuroprotection Research
Authors: Sebastian Küchlin, Gabriele Ihorst, Sven P. Heinrich, Pablo Márquez Neila, Philipp Albrecht, Martin J. Hug, Wolf A. Lagrèze
Journal: JAMA Neurology (2024)

This cohort study calculates clinical trial sample sizes powered by visual pathway outcomes of acute optic neuritis in neuroprotection research.
Eligibility and Projected Benefits of Rapid Initiation of Quadruple Therapy for Newly Diagnosed Heart Failure
Authors: Stephen J. Greene, Iyanuoluwa Ayodele, Jacob B. Pierce, Muhammad Shahzeb Khan, Sabra C. Lewsey, Clyde W. Yancy, Brooke Alhanti, Harriette G.C. Van Spall, Larry A. Allen, Gregg C. Fonarow
Journal: JACC Heart Failure (2024)

US nationwide estimates of the proportion of patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) eligible for quadruple medical therapy, and the associated benefits of rapid implementation, are not well characterized. This study sought to characterize the degree to which patients newly diagnosed with HFrEF are eligible for quadruple medical therapy, and the projected benefits of in-hospital initiation. Among patients hospitalized for newly diagnosed HFrEF in the Get With The Guidelines – Heart Failure registry from 2016-2023, eligibility criteria based on regulatory labeling, guidelines, and expert consensus documents were applied for ARNI, beta-blocker, MRA, and SGLT2i therapies. Of those eligible, the projected effect of quadruple therapy on 12-month mortality was modeled using treatment effects from pivotal clinical trials utilized by the ACC/AHA/HFSA heart failure guidelines, and compared with observed outcomes among patients treated with ACEI/ARB and beta-blockers. Of 33,036 patients newly diagnosed with HFrEF, 27,158 (82%) were eligible for quadruple therapy, and 30,613 (93%) were eligible for ≥3 components. From 2021-2023, of patients eligible for quadruple therapy, 15.3% were prescribed quadruple therapy and 41.5% were prescribed triple therapy. Among Medicare beneficiaries eligible for quadruple therapy, 12-month incidence of mortality was 24.7% and HF hospitalization was 22.2%. Applying the relative risk reductions in clinical trials, complete implementation of quadruple therapy by time of discharge was projected to yield absolute risk reductions in 12-month mortality of 10.4% (number-needed-to-treat [NNT]=10) compared with ACEI/ARB and beta-blocker, and 24.8% (NNT=4) compared with no GDMT. In this nationwide US cohort of patients hospitalized for newly diagnosed for HFrEF, more than 4 of 5 patients were projected as eligible for quadruple therapy at discharge, yet less than 1 in 6 were prescribed it. If clinical trial benefits can be fully realized, in-hospital initiation of quadruple medical therapy for newly diagnosed HFrEF would yield large absolute reductions in mortality.
Viable Vitreous Grafts of Whole Porcine Menisci for Transplant in the Knee and Temporomandibular Joints
Authors: Shangping Wang, Dustin Mueller, Peng Chen, Ge Pan, Marshall Wilson, Shuchun Sun, Zhenzhen Chen, Thomas Lee, Brooke Damon, R. Glenn Hepfer, Cherice Hill, Michael J. Kern, William M. Pullen, Yongren Wu, Kelvin G. M. Brockbank, Hai Yao
Journal: Advanced Healthcare Materials (2024)

Abstract The shortage of suitable donor meniscus grafts from the knee and temporomandibular joint (TMJ) impedes treatments for millions of patients. Vitrification offers a promising solution by transitioning these tissues into a vitreous state at cryogenic temperatures, protecting them from ice crystal damage using high concentrations of cryoprotectant agents (CPAs). However, vitrification's success is hindered for larger tissues (&gt;3 mL) due to challenges in CPA penetration. Dense avascular meniscus tissues require extended CPA exposure for adequate penetration; however, prolonged exposure becomes cytotoxic. Balancing penetration and reducing cell toxicity is required. To overcome this hurdle, a simulation‐based optimization approach is developed by combining computational modeling with microcomputed tomography (µCT) imaging to predict 3D CPA distributions within tissues over time accurately. This approach minimizes CPA exposure time, resulting in 85% viability in 4‐mL meniscal specimens, 70% in 10‐mL whole knee menisci, and 85% in 15‐mL whole TMJ menisci (i.e., TMJ disc) post‐vitrification, outperforming slow‐freezing methods (20%–40%), in a pig model. The extracellular matrix (ECM) structure and biomechanical strength of vitreous tissues remain largely intact. Vitreous meniscus grafts demonstrate clinical‐level viability (≥70%), closely resembling the material properties of native tissues, with long‐term availability for transplantation. The enhanced vitrification technology opens new possibilities for other avascular grafts.
Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development
Authors: Elena Dvoretskova, May C. Ho, Volker Kittke, Florian Neuhaus, Ilaria Vitali, Daniel D. Lam, Irene Delgado, Chao Feng, Miguel Torres, Juliane Winkelmann, Christian Mayer
Journal: Nature Neuroscience (2024)

Abstract The mammalian telencephalon contains distinct GABAergic projection neuron and interneuron types, originating in the germinal zone of the embryonic basal ganglia. How genetic information in the germinal zone determines cell types is unclear. Here we use a combination of in vivo CRISPR perturbation, lineage tracing and ChIP–sequencing analyses and show that the transcription factor MEIS2 favors the development of projection neurons by binding enhancer regions in projection-neuron-specific genes during mouse embryonic development. MEIS2 requires the presence of the homeodomain transcription factor DLX5 to direct its functional activity toward the appropriate binding sites. In interneuron precursors, the transcription factor LHX6 represses the MEIS2–DLX5-dependent activation of projection-neuron-specific enhancers. Mutations of Meis2 result in decreased activation of regulatory enhancers, affecting GABAergic differentiation. We propose a differential binding model where the binding of transcription factors at cis -regulatory elements determines differential gene expression programs regulating cell fate specification in the mouse ganglionic eminence.
rs822336 binding to C/EBPβ and NFIC modulates induction of PD-L1 expression and predicts anti-PD-1/PD-L1 therapy in advanced NSCLC
Authors: Giovanna Polcaro, Luigi Liguori, Valentina Manzo, Annalisa Chianese, Giuliana Donadio, Alessandro Caputo, Giosuè Scognamiglio, Federica Dell’Annunziata, Maddalena Langella, Graziamaria Corbi, Alessandro Ottaiano, Marco Cascella, Francesco Perri, Margot De Marco, Jessica Dal Col, Giovanni Nassa, Giorgio Giurato, Pio Zeppa, Amelia Filippelli, Gianluigi Franci, Fabrizio Dal Piaz, Valeria Conti, Stefano Pepe, Francesco Sabbatino
Journal: Molecular Cancer (2024)

Abstract Efficient predictive biomarkers are needed for immune checkpoint inhibitor (ICI)-based immunotherapy in non-small cell lung cancer (NSCLC). Testing the predictive value of single nucleotide polymorphisms (SNPs) in programmed cell death 1 ( PD-1 ) or its ligand 1 ( PD-L1 ) has shown contrasting results. Here, we aim to validate the predictive value of PD-L1 SNPs in advanced NSCLC patients treated with ICIs as well as to define the molecular mechanisms underlying the role of the identified SNP candidate. rs822336 efficiently predicted response to anti-PD-1/PD-L1 immunotherapy in advanced non-oncogene addicted NSCLC patients as compared to rs2282055 and rs4143815. rs822336 mapped to the promoter/enhancer region of PD-L1 , differentially affecting the induction of PD-L1 expression in human NSCLC cell lines as well as their susceptibility to HLA class I antigen matched PBMCs incubated with anti-PD-1 monoclonal antibody nivolumab. The induction of PD-L1 expression by rs822336 was mediated by a competitive allele-specificity binding of two identified transcription factors: C/EBPβ and NFIC. As a result, silencing of C/EBPβ and NFIC differentially regulated the induction of PD-L1 expression in human NSCLC cell lines carrying different rs822336 genotypes. Analysis by binding microarray further validated the competitive allele-specificity binding of C/EBPβ and NFIC to PD-L1 promoter/enhancer region based on rs822336 genotype in human NSCLC cell lines. These findings have high clinical relevance since identify rs822336 and induction of PD-L1 expression as novel biomarkers for predicting anti-PD-1/PD-L1-based immunotherapy in advanced NSCLC patients.
Inhibition of oxidized low-density lipoprotein with orticumab inhibits coronary inflammation and reduces residual inflammatory risk in psoriasis: a pilot randomized, double-blind placebo-controlled trial
Authors: Christopher J Farina, Michael H Davidson, Prediman K Shah, Charles Stark, Wenqi Lu, Cheerag Shirodaria, Timothy Wright, Charalambos A Antoniades, Jan Nilsson, Nehal N Mehta
Journal: Cardiovascular Research (2024)
British societies guideline on the management of emergencies in implantable left ventricular assist device recipients in transplant centres
Authors: Waqas Akhtar, Veronica Rial Baston, Marius Berman, Sai Bhagra, Colin Chue, Charles D. Deakin, Jonathan R. Dalzell, Joel Dunning, John Dunning, Roy S. Gardner, Kristine Kiff, Shishir Kore, Sern Lim, Guy MacGowan, Ian Naldrett, Marlies Ostermann, Sofia Pinto, Stephen Pettit, Fernando Riesgo Gil, Alex Rosenberg, Antonio Rubino, Rana Sayeed, Joao Sequeira, Neil Swanson, Steven Tsui, Christopher Walker, Stephen Webb, Andrew Woods, Rajamiyer Ventkateswaran, Christopher T. Bowles
Journal: Intensive Care Medicine (2024)

An implantable left ventricular assist device (LVAD) is indicated as a bridge to transplantation or recovery in the United Kingdom (UK). The mechanism of action of the LVAD results in a unique state of haemodynamic stability with diminished arterial pulsatility. The clinical assessment of an LVAD recipient can be challenging because non-invasive blood pressure, pulse and oxygen saturation measurements may be hard to obtain. As a result of this unusual situation and complex interplay between the device and the native circulation, resuscitation of LVAD recipients requires bespoke guidelines. Through collaboration with key UK stakeholders, we assessed the current evidence base and developed guidelines for the recognition of clinical deterioration, inadequate circulation and time-critical interventions. Such guidelines, intended for use in transplant centres, are designed to be deployed by those providing immediate care of LVAD patients under conditions of precipitous clinical deterioration. In summary, the Joint British Societies and Transplant Centres LVAD Working Group present the UK guideline on management of emergencies in implantable LVAD recipients for use in advanced heart failure centres. These recommendations have been made with a UK resuscitation focus but are widely applicable to professionals regularly managing patients with implantable LVADs.
Integration of polygenic and gut metagenomic risk prediction for common diseases
Authors: Yang Liu, Scott C. Ritchie, Shu Mei Teo, Matti O. Ruuskanen, Oleg Kambur, Qiyun Zhu, Jon Sanders, Yoshiki Vázquez-Baeza, Karin Verspoor, Pekka Jousilahti, Leo Lahti, Teemu Niiranen, Veikko Salomaa, Aki S. Havulinna, Rob Knight, Guillaume Méric, Michael Inouye
Journal: Nature Aging (2024)

Abstract Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18 years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.
<i>Lactiplantibacillus plantarum</i> strains KABP011, KABP012, and KABP013 modulate bile acids and cholesterol metabolism in humans
Authors: Teresa Padro, Victoria Santisteban, Pol Huedo, Montserrat Puntes, Meritxell Aguiló, Jordi Espadaler-Mazo, Lina Badimon
Journal: Cardiovascular Research (2024)

Probiotics with high bile salt hydrolase (BSH) activity have shown to promote cardiovascular health. However, their mechanism(s) of action remain poorly understood. Here, we performed a pilot exploratory study to investigate effects of a 4-week intervention with escalating doses of a BSH-active formula containing Lactiplantibacillus plantarum strains KABP011, KABP012, and KABP013 on bile acid (BA), lipid profile, and lipoprotein function.
Provision of Medications for Self-Managed Abortion Before and After the <i>Dobbs v Jackson Women’s Health Organization </i>Decision
Authors: Abigail R. A. Aiken, Elisa S. Wells, Rebecca Gomperts, James G. Scott
Journal: JAMA (2024)

The Supreme Court decision in Dobbs v Jackson Women's Health Organization overturned the right to choose abortion in the US, with at least 16 states subsequently implementing abortion bans or 6-week gestational limits. Prior research indicates that in the 6 months following Dobbs, approximately 32 360 fewer abortions were provided within the US formal health care setting. However, trends in the provision of medications for self-managed abortion outside the formal health care setting have not been studied.
Physiologic Effects of ECMO in Patients with Severe Acute Respiratory Distress Syndrome
Authors: Elena Spinelli, Marco Giani, Douglas Slobod, Bertrand Pavlovsky, Michela di Pierro, Stefania Crotti, Alfredo Lissoni, Giuseppe Foti, Giacomo Grasselli, Tommaso Mauri
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: Blood flow rate affects mixed venous oxygenation (SvO2) during venovenous extracorporeal membrane oxygenation (ECMO), with possible effects on the pulmonary circulation and the right heart function. Objectives: We aimed at describing the physiologic effects of different levels of SvO2 obtained by changing ECMO blood flow, in patients with severe ARDS receiving ECMO and controlled mechanical ventilation. Methods: Low (SvO2 target 70-75%), intermediate (SvO2 target 75-80%) and high (SvO2 target > 80%) ECMO blood flows were applied for 30 minutes in random order in 20 patients. Mechanical ventilation settings were left unchanged. The hemodynamic and pulmonary effects were assessed with pulmonary artery catheter and electrical impedance tomography (EIT). Measurements and Main Results: Cardiac output decreased from low to intermediate and to high blood flow/SvO2 (9.2 [6.2-10.9] vs 8.3 [5.9-9.8] vs 7.9 [6.5-9.1] L/min, p = 0.014), as well as mean pulmonary artery pressure (34 ± 6 vs 31 ± 6 vs 30 ± 5 mmHg, p < 0.001), and right ventricle stroke work index (14.2 ± 4.4 vs 12.2 ± 3.6 vs 11.4 ± 3.2 g*m/beat/m2, p = 0.002). Cardiac output was inversely correlated with mixed venous and arterial PO2 values (R2 = 0.257, p = 0.031 and R2 = 0.324, p = 0.05). Pulmonary artery pressure was correlated with decreasing mixed venous PO2 (R2 = 0.29, p <0.001) and with increasing cardiac output (R2 = 0.378 p < 0.007). Measures of ventilation/perfusion mismatch did not differ between the three steps. Conclusions: In severe ARDS patients, increased ECMO blood flow rate resulting in higher SvO2 decreases pulmonary artery pressure, cardiac output, and right heart workload.
Recent advances in the prevention and treatment of decompensated cirrhosis and acute-on-chronic liver failure (ACLF) and the role of biomarkers
Authors: Jonel Trebicka, Ruben Hernaez, Debbie Lindsay Shawcross, Alexander L Gerbes
Journal: Gut (2024)

The progression of cirrhosis with clinically significant portal hypertension towards decompensated cirrhosis remains clinically challenging and the evolution towards acute-on-chronic liver failure (ACLF), with one or more extrahepatic organ failures, is associated with very high mortality. In the last decade, significant progress has been made in the understanding of the mechanisms leading to decompensation and ACLF. As portal hypertension advances, bacterial translocation across an impaired gut barrier culminates in endotoxaemia, systemic inflammation and cirrhosis-associated immune dysfunction (CAID). Gut-derived systemic inflammation and CAID have become the logical targets for innovative therapies that prevent hepatic decompensation episodes and the progression to ACLF. Furthermore, classification of disease and biomarker discovery to personalise care have advanced in the field. This review discusses progress in biomarker discovery and personalisation of treatment in decompensated cirrhosis and ACLF.
Eukaryotic-driven directed evolution of Cas9 nucleases
Authors: Giulia Vittoria Ruta, Matteo Ciciani, Eyemen Kheir, Michele Domenico Gentile, Simone Amistadi, Antonio Casini, Anna Cereseto
Journal: Genome biology (2024)

Abstract Background Further advancement of genome editing highly depends on the development of tools with higher compatibility with eukaryotes. A multitude of described Cas9s have great potential but require optimization for genome editing purposes. Among these, the Cas9 from Campylobacter jejuni , CjCas9, has a favorable small size, facilitating delivery in mammalian cells. Nonetheless, its full exploitation is limited by its poor editing activity. Results Here, we develop a Eukaryotic Platform to Improve Cas Activity (EPICA) to steer weakly active Cas9 nucleases into highly active enzymes by directed evolution. The EPICA platform is obtained by coupling Cas nuclease activity with yeast auxotrophic selection followed by mammalian cell selection through a sensitive reporter system. EPICA is validated with CjCas9, generating an enhanced variant, UltraCjCas9, following directed evolution rounds. UltraCjCas9 is up to 12-fold more active in mammalian endogenous genomic loci, while preserving high genome-wide specificity. Conclusions We report a eukaryotic pipeline allowing enhancement of Cas9 systems, setting the ground to unlock the multitude of RNA-guided nucleases existing in nature.
Response to Correspondence to “Short‐course subcutaneous treatment with <scp>PQ</scp> Grass strongly improves symptom and medication scores in grass allergy”
Authors: P. J. de Kam, S. Zielen, J. A. Bernstein, U. Berger, M. Berger, M. Cuevas, D. Cypcar, A. Fuhr‐Horst, W. A. Greisner, M. Jandl, S. Laßmann, M. Worm, J. Matz, E. Sher, C. Smith, G. C. Steven, R. Mösges, M. H. Shamji, L. DuBuske, F. Borghese, K. Oluwayi, T. Zwingers, M. Seybold, O. Armfield, M. D. Heath, S. J. Hewings, M. F. Kramer, M. A. Skinner
Journal: Allergy (2024)

Data sharing is not applicable to this article as no new data were created or analyzed in this study.