tbuckley/cabot-search huggingface dataset:
Autoimmune Disorders Associated With Surgical Remission of Cushing’s Disease
Authors: Dennis Delasi Nyanyo, Masaaki Mikamoto, Francesca Galbiati, Ilan Remba-Shapiro, Kevin Bode, Sara Schoenfeld, Pamela S. Jones, Brooke Swearingen, Lisa B. Nachtigall
Journal: Annals of Internal Medicine (2024)

Background: Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described. Objective: To determine 1) the incidence of autoimmune disease in patients with CD after surgical remission compared with patients with nonfunctioning pituitary adenomas (NFPAs) and 2) the clinical presentation of and risk factors for development of autoimmune disease in CD after remission. Design: Retrospective matched cohort analysis. Setting: Academic medical center/pituitary center. Patients: Patients with CD with surgical remission and surgically treated NFPA. Measurements: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery. Assessment for hypercortisolemia included late-night salivary cortisol levels, 24-hour urine free cortisol (UFC) ratio (UFC value divided by the upper limit of the normal range for the assay), and dexamethasone suppression tests. Results: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery was higher in patients with CD (10.4% [95% CI, 5.7% to 15.1%]) than in those with NFPAs (1.6% [CI, 0% to 4.6%]) (hazard ratio, 7.80 [CI, 2.88 to 21.10]). Patients with CD showed higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and lower postoperative nadir serum cortisol levels (63.8 vs. 282.3 nmol/L) than patients with NFPAs. Compared with patients with CD without autoimmune disease, those who developed autoimmune disease had a lower preoperative 24-hour UFC ratio (2.7 vs. 6.3) and a higher prevalence of family history of autoimmune disease (41.2% vs. 20.9%). Limitation: The small sample of patients with autoimmune disease limited identification of independent risk factors. Conclusion: Patients achieving surgical remission of CD have higher incidence of autoimmune disease than age- and sex-matched patients with NFPAs. Family history of autoimmune disease is a potential risk factor. Adrenal insufficiency may be a trigger. Primary Funding Source: Recordati Rare Diseases Inc.
Phenotypic Expression and Clinical Outcomes in Patients With Arrhythmogenic Cardiomyopathies
Authors: Riccardo Bariani, Ilaria Rigato, Rudy Celeghin, Maria Bueno Marinas, Alberto Cipriani, Alessandro Zorzi, Valeria Pergola, Sabino Iliceto, Cristina Basso, Martina Perazzolo Marra, Domenico Corrado, Dario Gregori, Kalliopi Pilichou, Barbara Bauce
Journal: Journal of the American College of Cardiology (2024)
The impact of using reinforcement learning to personalize communication on medication adherence: findings from the REINFORCE trial
Authors: Julie C. Lauffenburger, Elad Yom-Tov, Punam A. Keller, Marie E. McDonnell, Katherine L. Crum, Gauri Bhatkhande, Ellen S. Sears, Kaitlin Hanken, Lily G. Bessette, Constance P. Fontanet, Nancy Haff, Seanna Vine, Niteesh K. Choudhry
Journal: npj Digital Medicine (2024)

Abstract Text messaging can promote healthy behaviors, like adherence to medication, yet its effectiveness remains modest, in part because message content is rarely personalized. Reinforcement learning has been used in consumer technology to personalize content but with limited application in healthcare. We tested a reinforcement learning program that identifies individual responsiveness (“adherence”) to text message content and personalizes messaging accordingly. We randomized 60 individuals with diabetes and glycated hemoglobin A1c [HbA1c] ≥ 7.5% to reinforcement learning intervention or control (no messages). Both arms received electronic pill bottles to measure adherence. The intervention improved absolute adjusted adherence by 13.6% (95%CI: 1.7%–27.1%) versus control and was more effective in patients with HbA1c 7.5- &lt; 9.0% (36.6%, 95%CI: 25.1%–48.2%, interaction p &lt; 0.001). We also explored whether individual patient characteristics were associated with differential response to tested behavioral factors and unique clusters of responsiveness. Reinforcement learning may be a promising approach to improve adherence and personalize communication at scale.
Airway epithelial cell response to RSV is mostly impaired in goblet and multiciliated cells in asthma
Authors: Aurore C A Gay, Martin Banchero, Orestes Carpaij, Tessa M Kole, Leonie Apperloo, Djoke van Gosliga, Putri Ayu Fajar, Gerard H Koppelman, Louis Bont, Rudi W Hendriks, Maarten van den Berge, Martijn C Nawijn
Journal: Thorax (2024)

In patients with asthma, respiratory syncytial virus (RSV) infections can cause disease exacerbation by infecting the epithelial layer of the airways, inducing subsequent immune response. The type I interferon antiviral response of epithelial cells upon RSV infection is found to be reduced in asthma in most-but not all-studies. Moreover, the molecular mechanisms causing the differences in the asthmatic bronchial epithelium in response to viral infection are poorly understood.
Focal adhesion protein Lasp1 links the Arp2/3 complex to adherens junctions and promotes motility of arthritic fibroblast-like synoviocytes
Authors: Denise Beckmann, Annika Krause, Uwe Hansen, Hans P Kiener, Thomas Karonitsch, Stephan Blüml, Joachim Kremerskothen, Hermann Pavenstädt, Thomas Pap, Adelheid Korb-Pap
Journal: Annals of the Rheumatic Diseases (2024)
Systemic inflammatory cytokine profiles in patients with gout during flare, intercritical and treat-to-target phases: TNFSF14 as new biomarker
Authors: Hang-Korng Ea, Brenda Kischkel, Twinu Wilson Chirayath, Viola Klück, Caroline Aparicio, Hoang-Uyen Loeung, Philippe Manivet, Tim Jansen, Mylène Zarka, Frédéric Lioté, Augustin Latourte, Thomas Bardin, Alan Gauffenic, Eric Vicaut, Tania Octavia Crișan, Mihai G Netea, Pascal Richette, Leo Joosten
Journal: Annals of the Rheumatic Diseases (2024)

Untreated gout is characterised by monosodium urate (MSU) crystal accumulation responsible for recurrent flares that are commonly separated by asymptomatic phases. Both phases are inflammatory conditions of variable intensity. Gout flares are self-limited inflammatory reactions involving multiple mediators. This study aimed to characterise the inflammatory profiles of gout at different phases.
Social media impact on athlete mental health: #RealityCheck
Authors: Margot Putukian, Cheri Blauwet, Alan Currie, Vincent Gouttebarge, David McDuff, Margo L Mountjoy, Scott Sloan, Abhinav Bindra, Richard Budgett, Lars Engebretsen, Rosemary Purcell
Journal: British Journal of Sports Medicine (2024)
Stellate cell-specific adhesion molecule protocadherin 7 regulates sinusoidal contraction
Authors: James K. Carter, Ming-Chao Tsai, Nicholas Venturini, Jiangting Hu, John J. Lemasters, Miguel Torres Martin, Daniela Sia, Shuang Wang, Youngmin A. Lee, Scott L. Friedman
Journal: Hepatology (2024)

Sustained inflammation and hepatocyte injury in chronic liver disease activate HSCs to transdifferentiate into fibrogenic, contractile myofibroblasts. We investigated the role of protocadherin 7 (PCDH7), a cadherin family member not previously characterized in the liver, whose expression is restricted to HSCs.
A modified Hospital Frailty Risk Score for patients with cirrhosis undergoing abdominal operations
Authors: Lucia Calthorpe, Sy Han Chiou, Jessica Rubin, Chiung-Yu Huang, Sandy Feng, Jennifer Lai
Journal: Hepatology (2024)

Background and Aims: Existing tools for perioperative risk stratification in patients with cirrhosis do not incorporate measures of comorbidity. The Hospital Frailty Risk Score (HFRS) is a widely used measure of comorbidity burden in administrative dataset analyses. However, it is not specific to patients with cirrhosis, and application of this index is limited by its complexity. Approach and Results: Adult patients with cirrhosis who underwent nontransplant abdominal operations were identified from the National Inpatient Sample, 2016–2018. Adjusted associations between HFRS and in-hospital mortality and length of stay were computed with logistic and Poisson regression. Lasso regularization was used to identify the components of the HFRS most predictive of mortality and develop a simplified index, the cirrhosis-HFRS. Of 10,714 patients with cirrhosis, the majority were male, the median age was 62 years, and 32% of operations were performed electively. HFRS was associated with an increased risk of both in-hospital mortality (OR=6.42; 95% CI: 4.93, 8.36) and length of stay (incidence rate ratio [IRR]=1.79; 95% CI: 1.72, 1.88), with adjustment. Using lasso, we found that a subset of 12 of the 109 ICD-10 codes within the HFRS resulted in superior prediction of mortality in this patient population (AUC = 0.89 vs. 0.79, p &lt; 0.001). Conclusions: While the 109-component HFRS was associated with adverse surgical outcomes, 12 components accounted for much of the association between the HFRS and mortality. We developed the cirrhosis-HFRS, a tool that demonstrates superior predictive accuracy for in-hospital mortality and more precisely reflects the specific comorbidity pattern of hospitalized patients with cirrhosis undergoing general surgery procedures.
Reply: Is the evidence convincing for the expansion of CHB treatment criteria to reduce the risk of HCC?
Authors: Daniel Q. Huang, Mindie H. Nguyen
Journal: Hepatology (2024)

We appreciate the comments from Dr. Zheng and colleagues regarding our work.1 We wish to clarify that we did not include patients with hepatitis C co-infection in our study. While we balanced multiple baseline characteristics, including age, sex, alanine aminotransferase, aspartate aminotransferase, DNA, HBeAg, platelet count, type 2 diabetes, and follow-up time, there may be confounders not adjusted for, as we have previously acknowledged in the discussion section of our manuscript. A prospective, randomized clinical trial may address these potential unmeasured confounders but requires a large sample size and long follow-up and may be challenging to execute. We believe that the data from this study has important implications for the expansion of treatment criteria to include some patients in the indeterminate phase of chronic hepatitis B.2 Preventing HCC with safe and effective antiviral therapy is likely to reduce the massive burden of HCC, and the time to act is now.3–5
Reply: Liver, heart, and kidney crosstalk in cirrhosis: POCUS is the focus
Authors: Madhumita Premkumar, Kamal Kajal, Manhal Izzy, Bhupendra K. Sihag
Journal: Hepatology (2024)

To the editor, We read with interest the letter by Agrawal and Ariga, and we thank them for the comments in response to our paper on point-of-care ultrasound in cirrhosis with hepatorenal syndrome-acute kidney injury).1 First, they comment on the lack of systolic dysfunction noted in this cohort. We noted left ventricular diastolic dysfunction in 53 (38%) patients, with 19 (14%), 25 (18%), and 9 (6%) having grades 1, 2, and 3 left ventricular diastolic dysfunction, respectively. Thus, 24% met the criteria for cirrhotic cardiomyopathy as per the 2020 cirrhotic cardiomyopathy consortium criteria.2 The study was carried out in an intensive care unit equipped with a point-of-care ultrasound device capable of tissue Doppler imaging but not speckle-tracking echocardiography. However, due to a low reported prevalence of abnormal global longitudinal strain (~1.5%) and lack of a universal definition of 'blunted response to stress,' we don't expect the lack of strain assessment to have affected the results.2,3 Alternatively, we assessed serial changes in velocity time integral, stroke volume, and cardiac index(CI) as surrogates for systolic function. A reduction in CI was shown in patients who failed to respond to terlipressin.2 The second observation related to mean arterial pressure that was maintained > 65-70 mm Hg in our cohort by optimizing volume status and, in this case, by use of a pressor agent (terlipressin). Therefore, we are unlikely to observe a significant reduction in mean arterial pressure in this setting. However, we found despite preserved mean arterial pressure, the CI may decline, which makes it a better indicator of tissue perfusion.4 Moreover, the authors brought up a valid point about the intravascular volume status for the study participants upon enrolment. When we used the inferior vena cava collapsibility index as a surrogate of volume status, there was no difference between responders (to terlipressin) and nonresponders at baseline, 48 h or 72 h after enrolment, as demonstrated in Table 2 in our manuscript. We respectfully disagree with the postulation of 2 distinct profiles in patients with cirrhosis and acute kidney injury, where responders to terlipressin were termed as patients with hepatorenal syndrome-acute kidney injury and nonresponders were termed as patients with hepato-cardio-renal syndrome. What may argue against the hepato-cardio-renal syndrome hypothesis is that, in our study, 18/34 (53%) of patients with cirrhotic cardiomyopathy still responded to terlipressin, but the response rate was reduced with high grades of left ventricular diastolic dysfunction. We believe that cardiac dysfunction in cirrhosis is a continuum that pertains to changes in myocardial contractility, structure, response to stress, renal perfusion, and tolerance for albumin and/or pressors, and this fascinating interplay warrants further investigation.
Letter to the Editor: Is the evidence convincing for the expansion of CHB treatment criteria to reduce the risk of HCC?
Authors: Zheng Li, Yi Zhang, Ying Li, Xi Chen, Jie Hu, Jiayun Yu, Yuzhu Hu, Shihong Nie, Nanjing Li, Qinglian Wen, Bingwen Zou
Journal: Hepatology (2024)

To the editor, Finding and removing the risk factors is one of the optimal strategies for the global prevention of HCC. With great enthusiasm, we read the significant cohort study1 by Huang et al published in Hepatology, in which a 70% reduction of HCC risk due to antiviral therapy was found among patients with indeterminate-phase chronic hepatitis B (CHB). The present results are an indispensable supplement for the relevant guideline in the expansion of the CHB treatment criteria to reduce the risk of HCC.1 If some key data could be further disclosed and analyzed, the strength of the evidence in this paper will be upgraded. The authors performed an inverse probability of treatment weighting analysis to balance baseline characteristics between the comparative groups in the Results section to reduce the risk of biases.1 The involved parameters for inverse probability of treatment weighting analyses included the presence of diabetes, alcohol, body mass index, and so on.1 However, some proven confounders were missing in the inverse probability of treatment weighting analyses, including some uncaptured risk factors and some uncaptured protective factors in Figure 1.2–5 The same flaws exist in the univariable and multivariable Cox proportional hazards regression analyses.1 As shown in Figure 1, the missing confounding factors of anti-HBV treatment (uncaptured risk/protective factors for HCC) include HDV and anti-HDV treatment, the use of glucagon-like peptide-1 receptor agonists for obesity, fatty liver disease and anti-fatty liver disease interventions, cardiovascular disease and use of statins, and smoking and well lifestyle interventions for smoking.2–5 The missing analyses of these uncaptured confounders are potential sources of biases. Therefore, supplementary analyses according to these uncaptured parameters should be performed to fully confirm the causality and its strength between anti-HBV treatment and the risk of HCC among patients with indeterminate-phase CHB.FIGURE 1: The multidimensional relationships among the risk factors/pathogeny, the protective factors/intervention, and the risk of HCC. Abbreviation: GLP-1, glucagon-like peptide-1.This multinational study1 by Huang et al is a necessary supplement for the future revision of relevant practice guidelines regarding antiviral treatment indications for patients with CHB. Therefore, we encourage the authors to make more efforts for the aforementioned data acquisition, sharing, and analysis, which is required to upgrade the strength of the evidence for the future revision of CHB guidelines.
Defining the activity of pro-reparative extracellular vesicles in wound healing based on miRNA payloads and cell type-specific lineage mapping
Authors: Dong Jun Park, Wooil Choi, Sakeef Sayeed, Robert A Dorschner, Joseph Rainaldi, Kayla Ho, Jenny Kezios, John P Nolan, Prashant Mali, Todd Costantini, Brian P Eliceiri
Journal: Molecular Therapy (2024)

Small extracellular vesicles (EVs) are released by cells and deliver biologically active payloads to coordinate the response of multiple cell types in cutaneous wound healing. Here we used a cutaneous injury model as a donor of pro-reparative EVs to treat recipient diabetic obese mice, a model of impaired wound healing. We established a functional screen for microRNAs (miRNAs) that increased the pro-reparative activity of EVs and identified a down-regulation of miR-425-5p in EVs in vivo and in vitro associated with the regulation of adiponectin. We tested a cell type-specific reporter of a tetraspanin CD9 fusion with GFP to lineage map the release of EVs from macrophages in the wound bed, based on the expression of miR-425-5p in macrophage-derived EVs and the abundance of macrophages in EV donor sites. Analysis of different promoters demonstrated that EV release under the control of a macrophage-specific promoter was most abundant and that these EVs were internalized by dermal fibroblasts. These findings suggested that pro-reparative EVs deliver miRNAs, such as miR-425-5p, that stimulate the expression of adiponectin that has insulin-sensitizing properties. We propose that EVs promote intercellular signaling between cell layers in the skin to resolve inflammation, induce proliferation of basal keratinocytes, and accelerate wound closure.
Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole-genome sequencing with histopathological features
Authors: Srinivasa Rao, Clare Verrill, Lucia Cerundolo, Nasullah Khalid Alham, Zeynep Kaya, Miriam O’Hanlon, Alicia Hayes, Adam Lambert, Martha James, Iain D. C. Tullis, Jane Niederer, Shelagh Lovell, Altan Omer, Francisco Lopez, Tom Leslie, Francesca Buffa, Richard J. Bryant, Alastair D. Lamb, Boris Vojnovic, David C. Wedge, Ian G. Mills, Dan J. Woodcock, Ian Tomlinson, Freddie C. Hamdy
Journal: Genome Medicine (2024)

Extension of prostate cancer beyond the primary site by local invasion or nodal metastasis is associated with poor prognosis. Despite significant research on tumour evolution in prostate cancer metastasis, the emergence and evolution of cancer clones at this early stage of expansion and spread are poorly understood. We aimed to delineate the routes of evolution and cancer spread within the prostate and to seminal vesicles and lymph nodes, linking these to histological features that are used in diagnostic risk stratification.
Global Epidemiology of Gallstones in the 21st Century: A Systematic Review and Meta-Analysis
Authors: Xin Wang, Wenqian Yu, Guoheng Jiang, Hongyu Li, Shiyi Li, Linjun Xie, Xuan Bai, Ping Cui, Qi Chen, Yanmei Lou, Li Zou, Sulian Li, Zhongfang Zhou, Chi Zhang, Peng Sun, Min Mao
Journal: Clinical Gastroenterology and Hepatology (2024)

Background & AimsGallstones are common and associated with substantial health and economic burden. We aimed to comprehensively evaluate the prevalence and incidence of gallstones in the 21st century.MethodsWe systematically searched PubMed and Embase to identify studies reporting the prevalence and/or incidence of gallstones between January 1, 2000, and November 18, 2023. Pooled prevalence and incidence were calculated using DerSimonian and Laird's random-effects model. We performed subgroup analyses and meta-regression based on age, sex, geographic location, population setting, and modality of detection to examine sources of heterogeneity.ResultsBased on 115 studies with 32,610,568 participants, the pooled prevalence of gallstones was 6.1% (95% CI, 5.6–6.5). Prevalence was higher in females vs males (7.6% vs 5.4%), in South America vs Asia (11.2% vs 5.1%), in upper-middle-income countries vs high-income countries (8.9% vs 4.0%), and with advancing age. On sensitivity analysis of population-based studies, the prevalence of gallstones was 5.5% (95% CI, 4.1–7.4; n = 44 studies), and when limiting subgroup analysis to imaging-based detection modalities, the prevalence was 6.7% (95% CI, 6.1–7.3; n = 101 studies). Prevalence has been stable over the past 20 years. Based on 12 studies, the incidence of gallstones was 0.47 per 100 person-years (95% CI, 0.37–0.51), without differences between males and females, and with increasing incidence in more recent studies.ConclusionsGlobally, 6% of the population have gallstones, with higher rates in females and in South America. The incidence of gallstones may be increasing. Our findings call for prioritizing research on the prevention of gallstones.