tbuckley/cabot-search huggingface dataset:
Limiting Overdistention or Collapse When Mechanically Ventilating Injured Lungs: A Randomized Study in a Porcine Model
Authors: Mayson L. A. Sousa, Bhushan H Katira, Sheena Bouch, Vanessa Hsing, Doreen Engelberts, Marcelo Amato, Martin Post, Laurent J. Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: It is unknown whether preventing overdistention or collapse is more important when titrating positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). Objective: To compare PEEP targeting either minimal overdistention, minimal collapse or using a compromise between collapse and overdistention in a randomized trial, and assess the impact on respiratory mechanics, gas exchange, inflammation, and hemodynamics. Methods: In a porcine model of ARDS, lung collapse and overdistention were estimated by electrical impedance tomography during a decremental PEEP titration. Pigs were randomized to three groups and ventilated for 12 hours: PEEP set at ≤3% of overdistention (low overdistention); ≤3% of collapse (low collapse); and crossing point of collapse and overdistention (crossing-point). Measurements and main results: Thirty-six pigs (12/group) were included. Median PEEP were 7(IQR:6-8)cmH2O, 11(10-11)cmH2O, and 15(12-16)cmH2O in the three groups, p<0.001. With low overdistension, 6(50%) pigs died whereas survival was 100% in both other groups. Cause of death was hemodynamic in nature, with high transpulmonary gradient and high epinephrine requirements. Compared to the other groups, pigs surviving with low overdistension had worse respiratory mechanics and gas exchange during the entire protocol. Minimal differences existed between crossing-point and low collapse animals in physiological parameters but postmortem alveolar density was more homogeneous in crossing-point. Inflammatory markers were not significantly different. Conclusions: PEEP to minimize overdistention resulted in high mortality in an animal model of ARDS. Minimizing collapse or choosing a compromise between collapse and overdistention may result in less lung injury, with potential benefits of the compromise approach.
Weight Loss Surgery Managed Blood Pressure for People With Obesity
Authors: Emily Harris
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Comparison of survival benefit and safety between surgery following conversion therapy versus surgery alone in patients with surgically resectable hepatocellular carcinoma at CNLC IIb/IIIa stage: a propensity score matching study
Authors: Zifeng Ma, Zhiyu Xiao, Pengfei yin, Kai Wen, Weidong Wang, Yongcong Yan, Zijian Lin, Zonglin Li, Haikuo Wang, Jianlong Zhang, Kai Mao
Journal: International Journal of Surgery (2024)

Objective: The objective of this study is to evaluate and compare the survival benefit and safety of surgery following conversion therapy versus surgery alone in patients diagnosed with surgically resectable hepatocellular carcinoma (HCC) at China Liver Cancer Staging (CNLC) IIb/IIIa stage. Methods: A total of 95 patients diagnosed with surgically resectable CNLC IIb/IIIa HCC were retrospectively enrolled in our study from November 2018 to December 2022. Among them, 30 patients underwent conversion therapy followed by hepatectomy, while the remaining 65 received surgery alone. The primary endpoint was recurrence-free survival (RFS). Propensity score matching (PSM) was employed to minimize bias in the retrospective analysis. Results: Compared to the surgery alone group, the conversion therapy group demonstrated a significantly prolonged median RFS (17.1 vs. 7.0 months; P =0.014), a reduced incidence of microvascular invasion (MVI, 23.3% vs. 81.5%; P &lt;0.001), and a comparable rate of achieving Textbook Outcome in Liver Surgery (TOLS, 83.3% vs. 76.9%; P =0.476). Multivariate analysis indicated that conversion therapy was independently associated with improved RFS after hepatectomy (HR=0.511, P =0.027). The same conclusions were obtained after PSM. Conclusions: The findings of our study offer preliminary evidence that preoperative conversion therapy significantly prolongs RFS in patients with surgically resectable HCC at CNLC IIb/IIIa stage. Furthermore, combining conversion therapy and hepatectomy represents a relatively safe treatment strategy.
ENIGMA Brain Morphometry in CHR-P—Risk Enrichment and Antipsychotics—Reply
Authors: Sophia Frangou, Shalaila S. Haas
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Lipoprotein(a), C-Reactive Protein, and Cardiovascular Risk in Primary and Secondary Prevention Populations
Authors: Aeron M. Small, Ashley Pournamdari, Giorgio E.M. Melloni, Benjamin M. Scirica, Deepak L. Bhatt, Itamar Raz, Eugene Braunwald, Robert P. Giugliano, Marc S. Sabatine, Gina M. Peloso, Nicholas A. Marston, Pradeep Natarajan
Journal: JAMA Cardiology (2024)

Elevated lipoprotein(a) (Lp[a]) is a putative causal risk factor for atherosclerotic cardiovascular disease (ASCVD). There are conflicting data as to whether Lp(a) may increase cardiovascular risk only in the presence of concomitant inflammation.
PHGDH is required for germinal center formation and is a therapeutic target in MYC-﻿﻿driven lymphoma
Authors: Annalisa D’Avola, Nathalie Legrave, Mylène Tajan, Probir Chakravarty, Ryan L. Shearer, Hamish W. King, Katarina Kluckova, Eric C. Cheung, Andrew J. Clear, Arief S. Gunawan, Lingling Zhang, Louisa K. James, James I. MacRae, John G. Gribben, Dinis P. Calado, Karen H. Vousden, John C. Riches
Journal: Journal of Clinical Investigation (2024)
Status check: next-generation sequencing for infectious-disease diagnostics
Authors: Kyle G Rodino, Patricia J Simner
Journal: Journal of Clinical Investigation (2024)

Next-generation sequencing (NGS) applications for the diagnostics of infectious diseases has demonstrated great potential with three distinct approaches: whole-genome sequencing (WGS), targeted NGS (tNGS), and metagenomic NGS (mNGS, also known as clinical metagenomics). These approaches provide several advantages over traditional microbiologic methods, though challenges still exist.
Hereditary hemorrhagic telangiectasia: from signaling insights to therapeutic advances
Authors: Tala Al Tabosh, Mohammad Al Tarrass, Laura Tourvieilhe, Alexandre Guilhem, Sophie Dupuis-Girod, Sabine Bailly
Journal: Journal of Clinical Investigation (2024)

Hereditary hemorrhagic telangiectsia (HHT) is an inherited vascular disorder with highly variable expressivity, affecting up to 1 in 5,000 individuals. This disease is characterized by small arteriovenous malformations (AVMs) in mucocutaneous areas (telangiectases) and larger visceral AVMs in the lungs, liver, and brain. HHT is caused by loss-of-function mutations in the BMP9-10/ENG/ALK1/SMAD4 signaling pathway. This Review presents up-to-date insights on this mutated signaling pathway and its crosstalk with proangiogenic pathways, in particular the VEGF pathway, that has allowed the repurposing of new drugs for HHT treatment. However, despite the substantial benefits of these new treatments in terms of alleviating symptom severity, this not-so-uncommon bleeding disorder still currently lacks any FDA- or European Medicines Agency-approved (EMA-approved) therapies.
Yoda1 opens the lymphatic path for craniosynostosis therapy
Authors: Aleksanteri Aspelund, Kari Alitalo
Journal: Journal of Clinical Investigation (2024)

The rediscovery of meningeal lymphatic vessels (MLVs) has sparked research interest in their function in numerous neurological pathologies. Craniosynostosis (CS) is caused by a premature fusion of cranial sutures during development. In this issue of the JCI, Matrongolo and colleagues show that Twist1-haploinsufficient mice that develop CS exhibit raised intracranial pressure, diminished cerebrospinal fluid (CSF) outflow, and impaired paravascular CSF-brain flow; all features that were associated with MLV defects and exacerbated pathology in mouse models of Alzheimer's disease. Activation of the mechanosensor Piezo1 with Yoda1 restored MLV function and CSF perfusion in CS models and in aged mice, opening an avenue for further development of therapeutics.
Symmetric Drug-Related Intertriginous and Flexural Exanthema
Authors: Miguel Mansilla Polo, Daniel Martín-Torregrosa
Journal: New England Journal of Medicine (2024)

A 42-year-old woman presented with a 10-day history of symmetric exanthema in her axillary, abdominal, and inguinal regions after taking a nonsteroidal antiinflammatory medication.
Cefepime–Taniborbactam in Complicated Urinary Tract Infection
Authors: Florian M Wagenlehner, Leanne B Gasink, Paul C McGovern, Greg Moeck, Patrick McLeroth, MaryBeth Dorr, Aaron Dane, Tim Henkel
Journal: New England Journal of Medicine (2024)

BackgroundCarbapenem-resistant Enterobacterales species and multidrug-resistant Pseudomonas aeruginosa are global health threats. Cefepime–taniborbactam is an investigational β-lactam and β-lactamase inhibitor combination with activity against Enterobacterales species and P. aeruginosa expressing serine and metallo-β-lactamases.MethodsIn this phase 3, double-blind, randomized trial, we assigned hospitalized adults with complicated urinary tract infection (UTI), including acute pyelonephritis, in a 2:1 ratio to receive intravenous cefepime–taniborbactam (2.5 g) or meropenem (1 g) every 8 hours for 7 days; this duration could be extended up to 14 days in case of bacteremia. The primary outcome was both microbiologic and clinical success (composite success) on trial days 19 to 23 in the microbiologic intention-to-treat (microITT) population (patients who had a qualifying gram-negative pathogen against which both study drugs were active). A prespecified superiority analysis of the primary outcome was performed after confirmation of noninferiority.Download a PDF of the Research Summary.ResultsOf the 661 patients who underwent randomization, 436 (66.0%) were included in the microITT population. The mean age of the patients was 56.2 years, and 38.1% were 65 years of age or older. In the microITT population, 57.8% of the patients had complicated UTI, 42.2% had acute pyelonephritis, and 13.1% had bacteremia. Composite success occurred in 207 of 293 patients (70.6%) in the cefepime–taniborbactam group and in 83 of 143 patients (58.0%) in the meropenem group. Cefepime–taniborbactam was superior to meropenem regarding the primary outcome (treatment difference, 12.6 percentage points; 95% confidence interval, 3.1 to 22.2; P=0.009). Differences in treatment response were sustained at late follow-up (trial days 28 to 35), when cefepime–taniborbactam had higher composite success and clinical success. Adverse events occurred in 35.5% and 29.0% of patients in the cefepime–taniborbactam group and the meropenem group, respectively, with headache, diarrhea, constipation, hypertension, and nausea the most frequently reported; the frequency of serious adverse events was similar in the two groups.ConclusionsCefepime–taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem. (Funded by Venatorx Pharmaceuticals and others; CERTAIN-1 ClinicalTrials.gov number, NCT03840148.) Quick Take Cefepime–Taniborbactam for Complicated UTI 2m 19s
Inhibition of CD40L with Frexalimab in Multiple Sclerosis
Authors: Patrick Vermersch, Cristina Granziera, Yang Mao-Draayer, Gary Cutter, Oleksandr Kalbus, Ivan Staikov, Michal Dufek, Stephane Saubadu, Raphael Bejuit, Philippe Truffinet, Biljana Djukic, Erik Wallstroem, Gavin Giovannoni
Journal: New England Journal of Medicine (2024)

The CD40-CD40L costimulatory pathway regulates adaptive and innate immune responses and has been implicated in the pathogenesis of multiple sclerosis. Frexalimab is a second-generation anti-CD40L monoclonal antibody being evaluated for the treatment of multiple sclerosis. In this phase 2, double-blind, randomized trial, we assigned, in a 4:4:1:1 ratio, participants with relapsing multiple sclerosis to receive 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose), or the matching placebos for each active treatment. The primary end point was the number of new gadolinium-enhancing T1-weighted lesions seen on magnetic resonance imaging at week 12 relative to week 8. Secondary end points included the number of new or enlarging T2-weighted lesions at week 12 relative to week 8, the total number of gadolinium-enhancing T1-weighted lesions at week 12, and safety. After 12 weeks, all the participants could receive open-label frexalimab. Of 166 participants screened, 129 were assigned to a trial group; 125 participants (97%) completed the 12-week double-blind period. The mean age of the participants was 36.6 years, 66% were women, and 30% had gadolinium-enhancing lesions at baseline. At week 12, the adjusted mean number of new gadolinium-enhancing T1-weighted lesions was 0.2 (95% confidence interval [CI], 0.1 to 0.4) in the group that received 1200 mg of frexalimab intravenously and 0.3 (95% CI, 0.1 to 0.6) in the group that received 300 mg of frexalimab subcutaneously, as compared with 1.4 (95% CI, 0.6 to 3.0) in the pooled placebo group. The rate ratios as compared with placebo were 0.11 (95% CI, 0.03 to 0.38) in the 1200-mg group and 0.21 (95% CI, 0.08 to 0.56) in the 300-mg group. Results for the secondary imaging end points were generally in the same direction as those for the primary analysis. The most common adverse events were coronavirus disease 2019 and headaches. In a phase 2 trial involving participants with multiple sclerosis, inhibition of CD40L with frexalimab had an effect that generally favored a greater reduction in the number of new gadolinium-enhancing T1-weighted lesions at week 12 as compared with placebo. Larger and longer trials are needed to determine the long-term efficacy and safety of frexalimab in persons with multiple sclerosis. (Funded by Sanofi; ClinicalTrials.gov number, NCT04879628.).
Electronic Nicotine-Delivery Systems for Smoking Cessation
Authors: Reto Auer, Anna Schoeni, Jean-Paul Humair, Isabelle Jacot-Sadowski, Ivan Berlin, Mirah J Stuber, Moa Lina Haller, Rodrigo Casagrande Tango, Anja Frei, Alexandra Strassmann, Philip Bruggmann, Florent Baty, Martin Brutsche, Kali Tal, Stéphanie Baggio, Julian Jakob, Nicolas Sambiagio, Nancy B Hopf, Martin Feller, Nicolas Rodondi, Aurélie Berthet
Journal: New England Journal of Medicine (2024)

Electronic nicotine-delivery systems - also called e-cigarettes - are used by some tobacco smokers to assist with quitting. Evidence regarding the efficacy and safety of these systems is needed.
High-Dose ERT, Rituximab, and Early HSCT in an Infant with Wolman’s Disease
Authors: Siawosh K Eskandari, Elisabeth G M Revenich, Dirk J Pot, Foekje de Boer, Marc Bierings, Francjan J van Spronsen, Peter M van Hasselt, Caroline A Lindemans, Charlotte M A Lubout
Journal: New England Journal of Medicine (2024)

Wolman's disease, a severe form of lysosomal acid lipase deficiency, leads to pathologic lipid accumulation in the liver and gut that, without treatment, is fatal in infancy. Although continued enzyme-replacement therapy (ERT) in combination with dietary fat restriction prolongs life, its therapeutic effect may wane over time. Allogeneic hematopoietic stem-cell transplantation (HSCT) offers a more definitive solution but carries a high risk of death. Here we describe an infant with Wolman's disease who received high-dose ERT, together with dietary fat restriction and rituximab-based B-cell depletion, as a bridge to early HSCT. At 32 months, the infant was independent of ERT and disease-free, with 100% donor chimerism in the peripheral blood.
Design of pH-responsive antimicrobial peptide melittin analog-camptothecin conjugates for tumor therapy
Authors: Sujie Huang, Yuxuan Gao, Ling Ma, Bo Jia, Wenhao Zhao, Yufan Yao, Wenyuan Li, Tongyi Lin, Rui Wang, Jingjing Song, Wei Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Melittin, a classical antimicrobial peptide, is a highly potent antitumor agent. However, its significant toxicity seriously hampers its application in tumor therapy. In this study, we developed novel melittin analogs with pH-responsive cell-penetrating and membrane-lytic activities by replacing arginine and lysine with histidine. After conjugation with camptothecin (CPT), CPT-AAM-1 and CPT-AAM-2 were capable of killing tumor cells by releasing CPT at low concentrations and disrupting cell membranes at high concentrations under acidic conditions. Notably, we found that the C-terminus of the melittin analogs was more suitable for drug conjugation than the N-terminus. CPT-AAM-1 significantly suppressed melanoma growth in vivo with relatively low toxicity. Collectively, the present study demonstrates that the development of antitumor drugs based on pH-responsive antimicrobial peptide-drug conjugates is a promising strategy.
Accurate determination of house dust mite sensitization in asthma and allergic rhinitis through cytometric detection of Der p 1 and Der p 2 binding on basophils (CytoBas)
Authors: Lin Hsin, Nirupama Varese, Pei Mun Aui, Bruce D. Wines, Anouk von Borstel, Laurent Mascarell, P. Mark Hogarth, Mark Hew, Robyn E. O’Hehir, Menno C. van Zelm
Journal: Journal of Allergy and Clinical Immunology (2024)

Graphical abstractAbstractBackgroundHouse dust mite (HDM) is the most common allergen trigger globally for allergic rhinitis and atopic asthma.ObjectivesTo expedite accurate confirmation of allergen sensitization, we designed fluorescent allergen tetramers to directly stain specific IgE on basophils to detect specific allergen sensitization using the flow cytometric CytoBas assay.MethodsRecombinant proteins of major HDM allergens (component), Der f 1, Der p 1, and Der p 2 were biotinylated and conjugated with fluorochrome streptavidins as tetramers. Blood samples from 64 patients who are HDM-allergic and 26 controls that are non–HDM-sensitized were incubated with allergen tetramers for evaluation of basophil binding (CytoBas) and activation (BAT) with flow cytometry.ResultsThe tetramers effectively bound and activated basophils from patients who are allergic but not from controls who are nonsensitized. CytoBas with Der p 1 as a single allergen had comparable sensitivity and specificity (92% and 100%) to BAT (91% and 100%) in detecting allergen sensitization, as did CytoBas with Der p 2 (95% and 96%) to BAT (95% and 87%). A positive staining for Der p 1 and/or Der p 2 in CytoBas was 100% sensitive and 96% specific for HDM allergy.ConclusionsCytoBas has diagnostic accuracy for group 1 and group 2 HDM allergens that is comparable to BAT, but with additional advantages of multiple allergen components in a single tube and no requirement for in vitro basophil activation. These findings endorse a single, multiplex CytoBas assay for accurate and component-resolved diagnosis of aeroallergen sensitization in patients with allergic asthma and/or rhinitis.
Role of ketogenic diet in neurodegenerative diseases focusing on Alzheimer diseases: The guardian angle
Authors: Hayder M. Al-kuraishy, Majid S. Jabir, Ali K. Albuhadily, Ali I. Al-Gareeb, Sabrean F. Jawad, Ayman A. Swelum, Najah R. Hadi
Journal: Ageing Research Reviews (2024)
Small-diameter vascular graft composing of core-shell structured micro-nanofibers loaded with heparin and VEGF for endothelialization and prevention of neointimal hyperplasia
Authors: Md Abdullah Al Fahad, Hyun-Yong Lee, Seongsu Park, Minji Choi, Prayas Chakma Shanto, Myeongki Park, Sang Ho Bae, Byong-Taek Lee
Journal: Biomaterials (2024)
Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy
Authors: Chenglin Liang, Ge Zhang, Linlin Guo, Xinyi Ding, Heng Yang, Hongling Zhang, Zhenzhong Zhang, Lin Hou
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy, but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration. Herein, we designed a cancer-associated fibroblasts (CAFs) triggered structure-transformable nano-assembly (HSD-P@V), which can directionally deliver valsartan (Val, CAFs regulator) and doxorubicin (DOX, senescence inducer) to the specific targets. In detail, DOX is conjugated with hyaluronic acid (HA) via diselenide bonds (Se-Se) to form HSD micelles, while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer, which is coated on Val nanocrystals (VNs) surface for improving the stability and achieving responsive release. Once arriving at tumor microenvironment and touching CAFs, HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment. VNs can degrade the extracellular matrix, leading to the enhanced penetration of HSD. HSD targets tumor cells, releases DOX to induce senescence, and recruits effector immune cells. Furthermore, senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy. In vitro and in vivo results show that the nano-assembly remarkably inhibits tumor growth as well as lung metastasis, and extends tumor-bearing mice survival. This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.