tbuckley/cabot-search huggingface dataset:
Illness and Ekphrastic Poetry
Authors: Rafael Campo
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 JAMA+ AI 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
Long-Term Outcomes of Component Separation for Abdominal Wall Hernia Repair
Authors: Brian T. Fry, Leah J. Schoel, Ryan A. Howard, Jyothi R. Thumma, Abigail L. Kappelman, Alexander K. Hallway, Anne P. Ehlers, Sean M. O’Neill, Michael A. Rubyan, Jenny M. Shao, Dana A. Telem
Journal: JAMA Surgery (2024)

Component separation is a reconstructive technique used to facilitate midline closure of large or complex ventral hernias. Despite a contemporary surge in popularity, the incidence and long-term outcomes after component separation remain unknown.
Doxycycline Postexposure Prophylaxis (DoxyPEP) for Bacterial STI Prevention
Authors: Muhammad H. Junejo, Julia L. Marcus, Kenneth A. Katz
Journal: JAMA Dermatology (2024)

This Viewpoint describes what dermatologists should know about doxycycline postexposure prophylaxis (doxyPEP) for bacterial sexually transmitted infection (STI) prevention, specifically syphilis, chlamydia, and gonorrhea.
Hydrogel Elastic Energy: A Stressor Triggering an Adaptive Stress‐Mediated Cell Response
Authors: Sara Lipari, Pasquale Sacco, Michela Cok, Francesca Scognamiglio, Maurizio Romano, Francesco Brun, Piero Giulio Giulianini, Eleonora Marsich, Finn L. Aachmann, Ivan Donati
Journal: Advanced Healthcare Materials (2024)

Abstract The crosstalk between the cells and the extracellular matrix (ECM) is bidirectional and consists of a pushing/pulling stretch exerted by the cells and a mechanical resistance counteracted by the surrounding microenvironment. It is widely recognized that the stiffness of the ECM, its viscoelasticity, and its overall deformation are the most important traits influencing the response of the cells. Here these three parameters are combined into a concept of elastic energy, which in biological terms represents the mechanical feedback that cells perceive when the ECM is deformed. It is shown that elastic energy is a stress factor that influences the response of cells in three‐dimensional (3D) cultures. Strikingly, the higher the elastic energy of the matrix and thus the mechanical feedback, the higher the stress state of the cells, which correlates with the formation of G3BP‐mediated stress granules. This condition is associated with an increase in alkaline phosphatase (ALP) activity but a decrease in gene expression and is mediated by the nuclear translocation of Yes‐associated protein (YAP). This work supports the importance of considering the elastic energy as mechano‐controller in regulating cellular stress state in 3D cultures.
Hypoxia‐reduced <scp>YAP</scp> phosphorylation enhances expression of <scp>Mucin5AC</scp> in nasal epithelial cells of chronic rhinosinusitis with nasal polyps
Authors: Bing Zhong, Jing Liu, Hsiao Hui Ong, Jintao Du, Feng Liu, Yafeng Liu, Luo Ba, Silu Sun, De Yun Wang
Journal: Allergy (2024)

Abstract Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is an upper respiratory disease characterized by persistent inflammation of the nasal mucosa. However, the mechanism of abnormal Mucin5AC expression by CRSwNP epithelial cells is not fully understood. Objective We investigated the potential role of yes‐associated protein (YAP) underlying the mechanism of excessive epithelial Mucin5AC expression in CRSwNP in a hypoxic model. Methods Tissue biopsies of CRSwNP ( n = 60), chronic rhinosinusitis without nasal polyps (CRSsNP) ( n = 9) and healthy controls ( n = 30) were investigated together with a well‐established hypoxic model of primary human nasal epithelial cells (hNECs). The expression levels of hypoxia inducible factor (HIF)‐1α and YAP, and the effect of the signaling axis on mucus secretion in hNECs were analyzed. Results We observed a significant elevated expression levels of YAP in patients with CRSwNP and CRSsNP compared to controls. In addition, HIF‐1α expression of CRSwNP was higher than that of control group. Under hypoxic conditions, HIF‐1α was found to regulate the upregulation of YAP in hNECs. Further investigations revealed that HIF‐1α facilitated the activation and nuclear localization of active‐YAP by reducing the phosphorylation of YAP. This mechanism appeared to be linked to HIF‐1α‐mediated inhibition of LATS 1 phosphorylation and subsequent YAP degradation. HIF‐1α was shown to promote the expression of P63 and the levels of Mucin5AC in hNECs by enhancing YAP activation. Conclusion Our findings indicated that hypoxia enhances YAP activation by decreasing p‐LATS 1 and YAP phosphorylation. This has the potential to impact on the proliferation of basal cells and the differentiation of goblet cells in CRSwNP, ultimately leading to a pathological condition characterized by excessive Mucin5AC expression.
Immunotherapy-Related Neurotoxicity in the Central Nervous System of Children with Cancer
Authors: Jiasen He, Jeremy Connors, Andrew Meador, Shuo Xu, Heather Meador, Hong Jiang, Juan Fueyo, Candelaria Gomez-Manzano, Gregory K Friedman, Wafik Zaky, Zsila Sadighi, John M Slopis, Ali H Ahmad
Journal: Neuro-Oncology (2024)

Abstract Significant gaps remain in our understanding of immunotherapy-related neurotoxicity in pediatric patients, largely because much of our knowledge comes from studies in adults. Accurately identifying the adverse effects of immunotherapy in children is also challenging, owing to variations in terminology and grading systems. Moreover, the manifestation of immunotherapy-related neurotoxicity differs greatly across different diseases, various modalities, dosages, and delivery methods. Combining immunotherapy with other treatments might improve outcomes but introduces new complexities and potential for increased toxicities. Additionally, pediatric patients with intracranial malignancy have unique responses to immunotherapies and distinct neurotoxicity compared to those with extracranial malignancy. Consequently, we must enhance our understanding of the pathophysiology, prevalence, severity, and management of immunotherapy’s neurotoxic effects in this vulnerable group. This review consolidates the current knowledge of immunotherapy-related neurotoxicity in pediatric oncology, highlighting various types of neurotoxicity including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and tumor inflammation-associated neurotoxicity (TIAN), among others. Furthermore, we examine the unique features of neurotoxicity associated with adoptive cellular therapy (ACT), antibody-based therapies, immune checkpoint inhibitors (ICIs), oncolytic viruses (OV), and cancer vaccines.
C-reactive protein promotes diabetic kidney disease via Smad3 mediated NLRP3 inflammasome activation
Authors: Yifan Wang, Yong-Ke You, Jianbo Guo, Jianan Wang, Baoyi Shao, Haidi Li, Xiaoming Meng, Hui-Yao Lan, Haiyong Chen
Journal: Molecular Therapy (2024)

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney diseases resulting in enormous socio-economic burden. Accumulated evidence has indicated that C-reactive protein (CRP) exacerbates DKD by enhancing renal inflammation and fibrosis through TGF-β/Smad3 signaling. NLRP3 inflammasome is the key sensor contributing to renal inflammation. However, whether CRP enhances inflammation in DKD via NLRP3 inflammasome-related pathway remains unknown. In this study, we demonstrate that CRP promotes DKD via Smad3-mediated NLRP3 inflammasome activation as mice overexpressing human CRP gene exhibits accelerated renal inflammation in diabetic kidneys, which is associated with the activation of Smad3 and NLRP3 inflammasomes. In contrast, blockade of CPR signaling with a neutralizing anti-CD32 antibody attenuates CRP-induced activation of Smad3 and NLRP3 in vitro. Importantly, genetic deletion or pharmacological inhibition of Smad3 also mitigates CRP-induced activation of NLRP3 in diabetic kidneys or in high glucose-treated cells. Mechanistically, we reveal that Smad3 binds to the NLRP3 gene promoter, which is enhanced by CRP. Taken together, we conclude that CRP induces renal inflammation in DKD via a Smad3-NLRP3 inflammasome-dependent mechanism. Thus, targeting CRP or Smad3-NLRP3 pathways may be a new therapeutic potential for DKD.
Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study.
Authors: F Lordick, M E Mauer, G Stocker, C A Cella, I Ben-Aharon, G Piessen, L Wyrwicz, G Al-Haidari, T Fleitas-Kanonnikoff, V Boige, R Lordick Obermannová, U M Martens, C Gomez-Martin, P Thuss-Patience, V Arrazubi, A Avallone, K K Shiu, P Artru, B Brenner, C Buges Sanchez, I Chau, S Lorenzen, S Daum, M Sinn, B Merelli, N C T van Grieken, M Nilsson, M Collienne, A Giraut, E Smyth
Journal: Annals of Oncology (2024)

Patients with gastro-oesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastro-oesophageal cancer. We hypothesised that nivolumab/ipilimumab would be more effective than adjuvant chemotherapy in high-risk (ypN+ and/or R1) patients with gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and resection. VESTIGE was an academic international, multicentre, open-label, randomised phase II trial evaluating the efficacy of adjuvant nivolumab/ipilimumab versus chemotherapy in gastro-oesophageal adenocarcinoma at high risk of recurrence. Patients were randomised 1 : 1 to receive standard adjuvant chemotherapy (same regimen as neoadjuvant) or nivolumab 3 mg/kg intravenously (i.v.) every 2 weeks plus ipilimumab 1 mg/kg i.v. every 6 weeks for 1 year. Key inclusion criteria included ypN+ and/or R1 status after neoadjuvant chemotherapy plus surgery. The primary endpoint was disease-free survival in the intent-to-treat population. Secondary endpoints included overall survival, locoregional and distant failure rates, and safety according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. The independent Data Monitoring Committee reviewed data from 189 of the planned 240 patients in June 2022 and recommended stopping recruitment due to futility. At the time of final analysis, median follow-up was 25.3 months for 195 patients (98 nivolumab/ipilimumab and 97 chemotherapy). Median disease-free survival for the nivolumab/ipilimumab group was 11.4 months [95% confidence interval (CI) 8.4-16.8 months] versus 20.8 months (95% CI 15.0-29.9 months) for the chemotherapy group, hazard ratio 1.55 (95% CI 1.07-2.25, one-sided P = 0.99). The 12-month disease-free survival rates were 47.1% and 64.0%, respectively. There were no toxicity concerns or excess early discontinuations. Nivolumab/ipilimumab did not improve disease-free survival compared with chemotherapy in patients with ypN+ and/or R1 gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and surgery.
Abstract 4137991: Association of the 2022 AHA/ACC/HFSA Heart Failure Staging and Cardiovascular and Kidney Outcomes in Patients with Diabetes and Kidney Disease: A Secondary Analysis of the SCORED Trial
Authors: Ayodele Odutayo, Deepak Bhatt, Vikas Sridhar, Michael Szarek, Michael Davies, Phillip Banks, Manon Girard, Bertram Pitt, Philippe Steg, David Cherney
Journal: Circulation (2024)

Introduction: The 2022 AHA/ACC/HFSA heart failure (HF) classification newly incorporates cardiac biomarkers to identify patients at risk of HF. Research Question: Given shared risk factors between HF and other cardiorenal events, the HF stages may also guide prognosis and management of cardiovascular (CV) and kidney-related events beyond HF. Aims: Examine the association of HF stage with CV and kidney events. Methods: SCORED was a randomized trial in diabetes with kidney disease comparing sotagliflozin (sota) v. placebo on CV death, hospitalizations for HF, and urgent HF visits. SCORED participants were grouped by HF stage post hoc . Stage A: No HF, normal cardiac biomarkers (NT-proBNP; &lt;125 pg/mL, hs-cTnT; &lt;14 ng/L) and normal cardiac structure/function by echocardiography. Stage B (pre-HF): No HF but elevated NTproBNP, hsTNT or abnormal echocardiography. Stage C/D: symptomatic HF. Endpoints of interest included the primary composite endpoint (CV death and HF-related events), major adverse CV events (MACE), and kidney-related composites (See Figure caption). Using Cox regression, we examined the association between HF stage and these endpoints, and whether the effect of sota v. placebo varied by HF stage. Results: There were 741 patients in stage A, 6560 in stage B (pre-HF) and 3283 in stage C/D (established HF). The mean NTproBNP and hs-cTnT increased with HF stage. Stepwise increases in HF stage were associated with a 2-4 fold higher incidence of the primary, MACE and kidney endpoints in the placebo group, although the incidence of the kidney-specific composite was similar in stage B and C/D (Figure). The relative risk reduction with sota v. placebo for all endpoints was similar irrespective of HF stage (p-interaction&gt;0.05), with higher absolute benefit in each HF stage (Figure). The absolute benefit for the kidney-specific endpoint was comparable for stage B and C/D. Conclusions: Increasing HF stage is associated with higher risk of HF, MACE, and kidney events, but the risk of kidney events is similar in stage B (pre-HF) and stage C/D (established HF). Sota has similar relative benefits for all endpoints, irrespective of HF stage, with a corresponding increase in absolute benefits at higher stages.
Statin Use During Concurrent Chemoradiotherapy for Advanced Nasopharyngeal Cancer
Authors: Jung-Min Yu, Chia-Lun Chang, Kuan-Chou Lin, Wan-Ming Chen, Ben-Chang Shia, Szu-Yuan Wu
Journal: Journal of the National Comprehensive Cancer Network (2024)

Background: The objective of this study was to assess the impact of statin use on overall survival (OS) and nasopharyngeal cancer (NPC)–specific survival in patients with advanced NPC who underwent standard concurrent chemoradiotherapy (CCRT). Patients and Methods: This propensity score matched cohort study used data from the Taiwan Cancer Registry Database and National Health Insurance Research Database to examine the impact of statin use during CCRT on both OS and NPC-specific survival. Results: Statin use during CCRT demonstrated significant and independent prognostic value for both OS and NPC-specific survival. The adjusted hazard ratio for all-cause mortality in the statin group compared with the nonstatin group was 0.48 (95% CI, 0.34–0.68; P &lt;.0001). Similarly, the adjusted hazard ratio for NPC-specific mortality in the statin group compared with the nonstatin group was 0.43 (95% CI, 0.29–0.65; P &lt;.0001). Rosuvastatin, atorvastatin, and lovastatin demonstrated significant efficacy in improving NPC-specific survival outcomes. Moreover, our findings indicate a dose–response relationship, with higher cumulative defined daily doses and greater daily intensity of statin use associated with reduced mortality. Conclusions: This study suggests an association between statin use during the CCRT period for NPC and potential enhancements in both OS and NPC-specific survival. Our findings indicate a possible survival benefit of rosuvastatin, atorvastatin, and lovastatin for patients with NPC undergoing CCRT. The observed dose–response relationship underscores the potential importance of higher statin use in mitigating NPC-specific mortality, but further research is needed to establish a definitive causal relationship.
Abstract 4138007: Mechanisms of Mitral Regurgitation in Fabry Disease
Authors: Alena Vecerova, Ales Linhart
Journal: Circulation (2024)

Introduction: Fabry disease, caused by mutations in the gene encoding alpha-galactosidase A, results in the accumulation of globotriaosylceramide (Gb3), leading to systemic complications including cardiac involvement such as mitral regurgitation (MR). The aim of this study is to investigate the association between MR severity and mitral leaflet morphology in Fabry disease patients. A cohort of 38 symptomatic Fabry disease patients with moderate or significant MR was followed up. Mitral leaflet morphology was categorized as normal, fibrodegenerative changes, or leaflet thickening. MR severity varied, with the primary cause being leaflet restriction. Additionally, left ventricular outflow tract obstruction (LVOTO) and annular dilatation were observed. The study suggests that MR in Fabry disease is primarily due to leaflet restriction, either through degenerative changes or leaflet thickening. This study investigates the association between MR severity and mitral leaflet morphology in Fabry disease patients. Methods: A cohort of 38 symptomatic Fabry disease patients with moderate or significant MR was followed up. Echocardiographic assessments were conducted to determine MR severity and categorize mitral leaflet morphology. Statistical analyses were performed to evaluate associations between MR severity and leaflet morphology. Echocardiographic assessments of the mitral valve were conducted using a Vivid E95 Cardiac Ultrasound and meticulously analyzed using the EchoPAC TM and TOMTEC Imaging Systems. A crucial aspect of the examination involved measuring all components of the mitral valve and determining the requisite angles to evaluate each mechanism thoroughly. Results: Most patients exhibited leaflet restriction as the primary cause of MR, with varying degrees of severity. Mitral leaflet morphology was categorized as normal in 15,8%, fibrodegenerative changes were in 31,5% and leaflet thickening in 52,7%. In addition, outflow tract obstruction (LVOTO) was observed in 15,7% but without systolic anterior motion (SAM) and annular dilatation (dilatation of anteroposterior annulus more than 35 mm in systole) was present in 66%. Conclusion: The study suggests that MR in Fabry disease is primarily attributed to leaflet restriction, either due to degenerative changes or leaflet thickening. An additional, albeit not unexpected, finding not always considered is the presence of anteroposterior annular dilatation in some cases.
Abstract 4137905: The association between prehospital epinephrine administration and short-term outcomes in patients with shockable out-of-hospital cardiac arrest and extracorporeal cardiopulmonary resuscitation: a propensity matched analysis
Authors: Shoji Kawakami, Koga Hidenobu, Tetsuhisa Yamada, Junichiro Nishi
Journal: Circulation (2024)

Background: In out-of-hospital cardiac arrest (OHCA) patients with an initial shockable rhythm, epinephrine increases the likelihood of return of spontaneous circulation (ROSC), but its effect on neurological outcome remains uncertain. Epinephrine administered before extracorporeal resuscitation (ECPR), which is a non-pharmacological method to obtain ROSC, may have worsened neurological outcome. Aim: To evaluate the impact of prehospital epinephrine administration on the prognosis of OHCA patients undergoing ECPR. Methods: This is a retrospective analysis of a cohort study from a multicenter, prospective registry of 81234 OHCA patients between 2014 and 2021. After the application of exclusion criteria, 1061 OHCA patients with an initial shockable rhythm and who underwent ECPR were eligible for this study. The primary outcome was favorable neurological outcome at 30 days after the OHCA and the secondary outcome was ROSC during transfer. Patients who did and did not receive prehospital epinephrine were propensity score-matched on the basis of age, gender, witness arrest, bystander-initiated CPR, dispatcher-assisted CPR, advanced airway management, call-to-defibrillation interval, year and district. Results: Among 1061 eligible patients, 442 patients received epinephrine and 619 patients did not. Matching was successful in achieving covariate balance as shown by a standardized difference of &lt;10% for all variables (329 matched pairs). The proportion of patients with prehospital ROSC was significantly higher in those who received prehospital epinephrine than those who did not (36 [8%] vs 31 [5%]; adjusted odds ratio [OR] after propensity score-matching, 1.96 [95% CI 1.05-3.67], p=0.03). The proportion of patients with favorable neurological outcome at 30 days was not significantly lower in those who received prehospital epinephrine than those who did not (34 [8%] vs 78 [13%]; adjusted OR after propensity score-matching, 0.78 [95% CI 0.45-1.37], p=0.39). Conclusion: In patients with shockable OHCA and ECPR, prehospital epinephrine administration was significantly associated with increased ROSC before hospital arrival and not significantly with decreased favorable neurological outcome at 30 days.