Journal of Internal Medicine最新文献

{"title":"IL-1β/DNA complex elevation distinguishes autoinflammatory disorders from autoimmune and infectious diseases","authors":"Anastasia-Maria Natsi, Efstratios Gavriilidis, Christina Antoniadou, Evangelos Papadimitriou, Vasileios Papadopoulos, Victoria Tsironidou, Dimitris Anastasios Palamidas, Loukas Chatzis, Eleni Sertaridou, Dimitrios Tsilingiris, Dimitrios T. Boumpas, Athanasios G. Tzioufas, Charalampos Papagoras, Konstantinos Ritis, Panagiotis Skendros","doi":"10.1111/joim.13809","DOIUrl":"10.1111/joim.13809","url":null,"abstract":"<p>IL-1-mediated autoinflammatory diseases (AID) consist of a heterogeneous group of innate immunity disorders [<span>1</span>]. Despite increasing awareness and research, differential diagnosis, particularly from other febrile conditions, allowing the timely initiation of appropriate therapy remains challenging because no diagnostic assay suitable for everyday clinical practice exists. In this context, several reports have shown that circulating levels of free IL-1 are neither informative nor correlated with disease causality and/or flare [<span>2</span>]. However, previous studies indicated that the release of neutrophil extracellular traps (NETs) carrying IL-1β on their DNA structure is a prominent feature of inflammatory attacks in familial Mediterranean fever and other AID [<span>3, 4</span>]. Despite the established role of microscopy methods to study NETs [<span>5</span>], we sought to develop a simple assay, not dependent on freshly isolated neutrophils, which could easily determine the amount of IL-1β being in complex with extracellular DNA in circulation and evaluate its diagnostic utility in AID.</p><p>First, we confirmed by immunofluorescence microscopy that neutrophils, ex vivo isolated from representative patients suffering from inflammatory attacks of a typical AID, were characterized by spontaneous formation of IL-1β-enriched NETs (Fig. 1A–F). These results were consistent with the high amounts of IL-1β detected in complex with circulating DNA, as determined by a novel “in-house” IL-1β/DNA complex-specific ELISA assay in plasma samples concurrently isolated from the same patients (Fig. 1G). Additionally, the mean fluorescence intensity of microscopy sections correlated well with IL-1β/DNA complex values (Fig. 1H).</p><p>Next, considering that circulating IL-1β/DNA complex levels were consistent with IL-1β-bearing NETs, we extended our study by evaluating the IL-1β/DNA complex assay in different control groups of well-characterized patients with inflammatory disorders. Significantly higher values of IL-1β/DNA complexes in AID flare, compared to active autoimmune rheumatic diseases (ARD), acute infections (INF), and healthy individuals were observed (Fig. 1I). These results were further supported by immunofluorescence microscopy in randomly selected patients from the control groups (Fig. S1). A cut-off of >0.050 arbitrary units was sufficient to distinguish AID from either INF or ARD with a sensitivity of 92.0% and a specificity of 86.4% (AUC of the ROC 0.922 ± 0.042; <i>p</i> < 10<sup>−6</sup>) (Fig. 1J, Table S1). Of note, levels of circulating free IL-1β and cell-free DNA, as measured simultaneously by a commercially available IL-1β ELISA and SYTOX-green dye, respectively, did not differ among groups (Fig. 1K,L). Moreover, in the total number of samples, IL-1β/DNA complex values did not correlate with free IL-1β (Fig. 1M) or cell-free DNA levels (Fig. 1N). These data suggest that the IL-1β/DNA complex assay can selectively ","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 3","pages":"298-301"},"PeriodicalIF":9.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13809","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trend in prevalence, associated risk factors, and longitudinal outcomes of sarcopenia in China: A national cohort study","authors":"Weida Qiu,&nbsp;Anping Cai,&nbsp;Liwen Li,&nbsp;Yingqing Feng","doi":"10.1111/joim.13808","DOIUrl":"10.1111/joim.13808","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To estimate the contemporary trend in the prevalence of sarcopenia and evaluate its risk factors and the longitudinal associations with multiple chronic conditions and mortality among Chinese middle-aged and older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a nationwide, prospective cohort study using data from the China Health and Retirement Longitudinal Study. The definition of sarcopenia was based on the Asian Working Group for Sarcopenia 2019 algorithm. In the cross-sectional analysis, we estimated the trend in the weighted prevalence of sarcopenia from 2011 to 2015 and examined the associated risk factors for sarcopenia severity in 2011. In the longitudinal analysis, we assessed the longitudinal associations between sarcopenia and 14 chronic conditions and mortality during a 9-year follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The weighted prevalence of sarcopenia remained consistently high in the overall population from 2011 (15.9%, 95% confidence intervals [CI]: 15.1, 16.6) to 2015 (15.0%, 95% CI: 14.3, 15.6; <i>p</i> for trend = 0.075). A range of risk factors were independently associated with the severity of sarcopenia, including older age, female sex, lower socioeconomic status, smoking status, malnutrition, and several chronic conditions. Possible sarcopenic and sarcopenic individuals had higher odds of several chronic conditions (i.e., heart disease, chronic lung disease, and memory-related disease) and increased risks of mortality (possible sarcopenia: odds ratios (OR): 1.66, 95% CI: 1.37, 2.00; sarcopenia: OR: 1.69, 95% CI: 1.36, 2.11) in 9 years of follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The prevalence of sarcopenia remained consistently high in the investigated population. Various risk factors were significantly associated with a higher prevalence of sarcopenia. Sarcopenic individuals had higher odds of several chronic conditions and increased risks of mortality, highlighting that the urgent need for dedicated efforts to improve the management of sarcopenic patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 2","pages":"156-167"},"PeriodicalIF":9.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MASLD and MASH at the crossroads of hepatology trials and cardiorenal metabolic trials","authors":"Faiez Zannad,&nbsp;Arun J. Sanyal,&nbsp;Javed Butler,&nbsp;João Pedro Ferreira,&nbsp;Nicolas Girerd,&nbsp;Veronica Miller,&nbsp;Ambarish Pandey,&nbsp;Chirag R. Parikh,&nbsp;Vlad Ratziu,&nbsp;Zobair M. Younossi,&nbsp;Stephen A. Harrison","doi":"10.1111/joim.13793","DOIUrl":"10.1111/joim.13793","url":null,"abstract":"<p>Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease. Conversely, patients with cardiometabolic conditions have a high prevalence of SLD. In addition to epidemiological evidence linking many of these conditions, there is evidence of shared pathophysiological processes. In December 2022, a unique multi-stakeholder, multi-specialty meeting, called MOSAIC (Metabolic multi Organ Science Accelerating Innovation in Clinical Trials) was convened to foster collaboration across metabolic, hepatology, nephrology and CV disorders. One of the goals of the meeting was to consider approaches to drug development that would speed regulatory approval of treatments for multiple disorders by combining liver and cardiorenal endpoints within a single study. Non-invasive tests, including biomarkers and imaging, are needed in hepatic and cardiorenal trials. They can be used as trial endpoints, to enrich trial populations, to diagnose and risk stratify patients and to assess treatment efficacy and safety. Although they are used in proof of concept and phase 2 trials, they are often not acceptable for regulatory approval of therapies. The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 1","pages":"24-38"},"PeriodicalIF":11.1,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13793","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelets as an inter-player between hyperlipidaemia and atherosclerosis","authors":"Nailin Li","doi":"10.1111/joim.13794","DOIUrl":"10.1111/joim.13794","url":null,"abstract":"<p>Platelet hyperreactivity and hyperlipidaemia contribute significantly to atherosclerosis. Thus, it is desirable to review the platelet–hyperlipidaemia interplay and its impact on atherogenesis. Native low-density lipoprotein (nLDL) and oxidized LDL (oxLDL) are the key proatherosclerotic components of hyperlipidaemia. nLDL binds to the platelet-specific LDL receptor (LDLR) ApoE-R2′, whereas oxLDL binds to the platelet-expressed scavenger receptor CD36, lectin-type oxidized LDLR 1 and scavenger receptor class A 1. Ligation of nLDL/oxLDL induces mild platelet activation and may prime platelets for other platelet agonists. Platelets, in turn, can modulate lipoprotein metabolisms. Platelets contribute to LDL oxidation by enhancing the production of reactive oxygen species and LDLR degradation via proprotein convertase subtilisin/kexin type 9 release. Platelet-released platelet factor 4 and transforming growth factor β modulate LDL uptake and foam cell formation. Thus, platelet dysfunction and hyperlipidaemia work in concert to aggravate atherogenesis. Hypolipidemic drugs modulate platelet function, whereas antiplatelet drugs influence lipid metabolism. The research prospects of the platelet–hyperlipidaemia interplay in atherosclerosis are also discussed.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 1","pages":"39-52"},"PeriodicalIF":11.1,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-throughput molecular assays for inclusion in personalised oncology trials – State-of-the-art and beyond","authors":"Anders Edsjö,&nbsp;Hege G. Russnes,&nbsp;Janne Lehtiö,&nbsp;David Tamborero,&nbsp;Eivind Hovig,&nbsp;Albrecht Stenzinger,&nbsp;Richard Rosenquist,&nbsp;the PCM4EU consortium","doi":"10.1111/joim.13785","DOIUrl":"10.1111/joim.13785","url":null,"abstract":"<p>In the last decades, the development of high-throughput molecular assays has revolutionised cancer diagnostics, paving the way for the concept of personalised cancer medicine. This progress has been driven by the introduction of such technologies through biomarker-driven oncology trials. In this review, strengths and limitations of various state-of-the-art sequencing technologies, including gene panel sequencing (DNA and RNA), whole-exome/whole-genome sequencing and whole-transcriptome sequencing, are explored, focusing on their ability to identify clinically relevant biomarkers with diagnostic, prognostic and/or predictive impact. This includes the need to assess complex biomarkers, for example microsatellite instability, tumour mutation burden and homologous recombination deficiency, to identify patients suitable for specific therapies, including immunotherapy. Furthermore, the crucial role of biomarker analysis and multidisciplinary molecular tumour boards in selecting patients for trial inclusion is discussed in relation to various trial concepts, including drug repurposing. Recognising that today's exploratory techniques will evolve into tomorrow's routine diagnostics and clinical study inclusion assays, the importance of emerging technologies for multimodal diagnostics, such as proteomics and in vivo drug sensitivity testing, is also discussed. In addition, key regulatory aspects and the importance of patient engagement in all phases of a clinical trial are described. Finally, we propose a set of recommendations for consideration when planning a new precision cancer medicine trial.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"295 6","pages":"785-803"},"PeriodicalIF":11.1,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13785","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses","authors":"Eirini Apostolou,&nbsp;Anders Rosén","doi":"10.1111/joim.13792","DOIUrl":"10.1111/joim.13792","url":null,"abstract":"<p>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease presenting with severe fatigue, post-exertional malaise, and cognitive disturbances—among a spectrum of symptoms—that collectively render the patient housebound or bedbound. Epigenetic studies in ME/CFS collectively confirm alterations and/or malfunctions in cellular and organismal physiology associated with immune responses, cellular metabolism, cell death and proliferation, and neuronal and endothelial cell function. The sudden onset of ME/CFS follows a major stress factor that, in approximately 70% of cases, involves viral infection, and ME/CFS symptoms overlap with those of long COVID. Viruses primarily linked to ME/CFS pathology are the symbiotic herpesviruses, which follow a bivalent latent–lytic lifecycle. The complex interaction between viruses and hosts involves strategies from both sides: immune evasion and persistence by the viruses, and immune activation and viral clearance by the host. This dynamic interaction is imperative for herpesviruses that facilitate their persistence through epigenetic regulation of their own and the host genome. In the current article, we provide an overview of the epigenetic signatures demonstrated in ME/CFS and focus on the potential strategies that latent viruses—particularly Epstein–Barr virus—may employ in long-term epigenetic reprograming in ME/CFS. Epigenetic studies could aid in elucidating relevant biological pathways impacted in ME/CFS and reflect the physiological variations among the patients that stem from environmental triggers, including exogenous viruses and/or altered viral activity.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 1","pages":"93-115"},"PeriodicalIF":11.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13792","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140828414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of integrated person-centered interventions for older people's care: Review of Swedish experiences and experts’ perspective","authors":"Mariam Kirvalidze,&nbsp;Anne-Marie Boström,&nbsp;Ann Liljas,&nbsp;Megan Doheny,&nbsp;Anne Hendry,&nbsp;Brendan McCormack,&nbsp;Laura Fratiglioni,&nbsp;Sulin Ali,&nbsp;Zahra Ebrahimi,&nbsp;Sölve Elmståhl,&nbsp;Maria Eriksdotter,&nbsp;Pascal Gläske,&nbsp;Lena-Karin Gustafsson,&nbsp;Åsa Hedberg Rundgren,&nbsp;Helena Hvitfeldt,&nbsp;Carin Lennartsson,&nbsp;Lena Marmstål Hammar,&nbsp;Gunnar H Nilsson,&nbsp;Peter Nilsson,&nbsp;Joakim Öhlén,&nbsp;Anna Sandgren,&nbsp;Annika Söderman,&nbsp;Karl Swedberg,&nbsp;Nicoline Vackerberg,&nbsp;Davide Liborio Vetrano,&nbsp;Helle Wijk,&nbsp;Janne Agerholm,&nbsp;Amaia Calderón-Larrañaga","doi":"10.1111/joim.13784","DOIUrl":"10.1111/joim.13784","url":null,"abstract":"<p>Older adults have multiple medical and social care needs, requiring a shift toward an integrated person-centered model of care. Our objective was to describe and summarize Swedish experiences of integrated person-centered care by reviewing studies published between 2000 and 2023, and to identify the main challenges and scientific gaps through expert discussions. Seventy-three publications were identified by searching MEDLINE and contacting experts. Interventions were categorized using two World Health Organization frameworks: (1) Integrated Care for Older People (ICOPE), and (2) Integrated People-Centered Health Services (IPCHS). The included 73 publications were derived from 31 unique and heterogeneous interventions pertaining mainly to the micro- and meso-levels. Among publications measuring mortality, 15% were effective. Subjective health outcomes showed improvement in 24% of publications, morbidity outcomes in 42%, disability outcomes in 48%, and service utilization outcomes in 58%. Workshop discussions in Stockholm (Sweden), March 2023, were recorded, transcribed, and summarized. Experts emphasized: (1) lack of rigorous evaluation methods, (2) need for participatory designs, (3) scarcity of macro-level interventions, and (4) importance of transitioning from person- to people-centered integrated care. These challenges could explain the unexpected weak beneficial effects of the interventions on health outcomes, whereas service utilization outcomes were more positively impacted. Finally, we derived a list of recommendations, including the need to engage care organizations in interventions from their inception and to leverage researchers’ scientific expertise. Although this review provides a comprehensive snapshot of interventions in the context of Sweden, the findings offer transferable perspectives on the real-world challenges encountered in this field.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"295 6","pages":"804-824"},"PeriodicalIF":11.1,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13784","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140654913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preoperative prediction of metastatic pheochromocytoma and paraganglioma using clinical, genetic, and biochemical markers: A cohort study","authors":"Seung Shin Park,&nbsp;Chang Ho Ahn,&nbsp;Seunghoo Lee,&nbsp;Woochang Lee,&nbsp;Won Woong Kim,&nbsp;Yu-Mi Lee,&nbsp;Su Jin Kim,&nbsp;Tae-Yon Sung,&nbsp;Kyu Eun Lee,&nbsp;Jung Hee Kim,&nbsp;Seung Hun Lee,&nbsp;Jung-Min Koh","doi":"10.1111/joim.13791","DOIUrl":"10.1111/joim.13791","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The prevalence of metastatic pheochromocytoma and paraganglioma (PPGL) is approximately 15%–20%. Although there are indicators to assess metastatic risks, none of them predict metastasis reliably. Therefore, we aimed to develop and validate a scoring system using clinical, genetic, and biochemical risk factors to preoperatively predict the metastatic risk of PPGL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the cross-sectional cohort (<i>n</i> = 180), clinical, genetic, and biochemical risk factors for metastasis were identified using multivariate logistic regression analysis, and a novel scoring system was developed. The scoring system was validated and compared with the age, size of tumor, extra-adrenal location, and secretory type (ASES) score in the longitudinal cohort (<i>n</i> = 114).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the cross-sectional cohort, pseudohypoxia group-related gene variants (<i>SDHB</i>, <i>SDHD</i>, or <i>VHL</i>), methoxytyramine &gt;0.16 nmol/L, and tumor size &gt;6.0 cm were independently associated with metastasis after multivariate logistic regression. Using them, the gene variant, methoxytyramine, and size of tumor (GMS) score were developed. In the longitudinal cohort, Harrell's concordance index of the GMS score (0.873, 95% confidence interval [CI]: 0.738–0.941) was higher than that of the ASES score (0.713, 95% CI: 0.567–0.814, <i>p</i> = 0.007). In the longitudinal cohort, a GMS score ≥2 was significantly associated with a higher risk of metastasis (hazard ratio = 25.07, 95% CI: 5.65–111.20). A GMS score ≥2 (<i>p</i> &lt; 0.001), but not ASES score ≥2 (<i>p</i> = 0.090), was associated with shorter progression-free survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The GMS scoring system, which integrates gene variant, methoxytyramine level, and tumor size, provides a valuable preoperative approach to assess metastatic risk in PPGL.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 1","pages":"68-79"},"PeriodicalIF":11.1,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140661414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early transfusion patterns improve the Molecular International Prognostic Scoring System (IPSS-M) prediction in myelodysplastic syndromes","authors":"Maria Creignou,&nbsp;Elsa Bernard,&nbsp;Alessandro Gasparini,&nbsp;Anna Tranberg,&nbsp;Gabriele Todisco,&nbsp;Pedro Luis Moura,&nbsp;Elisabeth Ejerblad,&nbsp;Lars Nilsson,&nbsp;Hege Garelius,&nbsp;Petar Antunovic,&nbsp;Fryderyk Lorenz,&nbsp;Bengt Rasmussen,&nbsp;Gunilla Walldin,&nbsp;Teresa Mortera-Blanco,&nbsp;Monika Jansson,&nbsp;Magnus Tobiasson,&nbsp;Chiara Elena,&nbsp;Jacqueline Ferrari,&nbsp;Anna Gallì,&nbsp;Sara Pozzi,&nbsp;Luca Malcovati,&nbsp;Gustaf Edgren,&nbsp;Michael J. Crowther,&nbsp;Martin Jädersten,&nbsp;Elli Papaemmanuil,&nbsp;Eva Hellström-Lindberg","doi":"10.1111/joim.13790","DOIUrl":"10.1111/joim.13790","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The Molecular International Prognostic Scoring System (IPSS-M) is the new gold standard for diagnostic outcome prediction in patients with myelodysplastic syndromes (MDS). This study was designed to assess the additive prognostic impact of dynamic transfusion parameters during early follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrieved complete transfusion data from 677 adult Swedish MDS patients included in the IPSS-M cohort. Time-dependent erythrocyte transfusion dependency (E-TD) was added to IPSS-M features and analyzed regarding overall survival and leukemic transformation (acute myeloid leukemia). A multistate Markov model was applied to assess the prognostic value of early changes in transfusion patterns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Specific clinical and genetic features were predicted for diagnostic and time-dependent transfusion patterns. Importantly, transfusion state both at diagnosis and within the first year strongly predicts outcomes in both lower (LR) and higher-risk (HR) MDSs. In multivariable analysis, 8-month landmark E-TD predicted shorter survival independently of IPSS-M (<i>p</i> &lt; 0.001). A predictive model based on IPSS-M and 8-month landmark E-TD performed significantly better than a model including only IPSS-M. Similar trends were observed in an independent validation cohort (<i>n</i> = 218). Early transfusion patterns impacted both future transfusion requirements and outcomes in a multistate Markov model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The transfusion requirement is a robust and available clinical parameter incorporating the effects of first-line management. In MDS, it provides dynamic risk information independently of diagnostic IPSS-M and, in particular, clinical guidance to LR MDS patients eligible for potentially curative therapeutic intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 1","pages":"53-67"},"PeriodicalIF":11.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.13790","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140672265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational diabetes mellitus is associated with greater incidence of dementia during long-term post-partum follow-up","authors":"Yang Zhang,&nbsp;Darui Gao,&nbsp;Ying Gao,&nbsp;Jing Li,&nbsp;Chenglong Li,&nbsp;Yang Pan,&nbsp;Yongqian Wang,&nbsp;Junqing Zhang,&nbsp;Fanfan Zheng,&nbsp;Wuxiang Xie","doi":"10.1111/joim.13787","DOIUrl":"10.1111/joim.13787","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The impact of gestational diabetes mellitus (GDM) on incident dementia is unknown. Our aim was to evaluate the relationship between GDM and all-cause dementia and the mediating effects of chronic diseases on this relationship.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective cohort study included women from the UK Biobank who were grouped based on GDM history. Multivariate Cox proportional hazard models were used to explore the associations between GDM and dementia. We further analysed the mediating effects of chronic diseases on this relationship and the interactions of covariates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1292 women with and 204,171 women without a history of GDM were included. During a median follow-up period of 45 years after first birth, 2921 women were diagnosed with dementia. Women with a GDM history had a 67% increased risk of incident dementia (hazard ratio 1.67, 95% confidence interval: 1.03–2.69) compared with those without a GDM history. According to mediation analyses, type 2 diabetes, coronary heart disease, chronic kidney disease and comorbidities (diagnosed with any two of the three diseases) explained 34.5%, 8.4%, 5.2% and 18.8% of the mediating effect on the relationship. Subgroup analyses revealed that physical activity modified the association between GDM history and dementia (<i>p</i> for interaction = 0.030). Among physically inactive women, GDM was significantly associated with incident dementia; however, this association was not observed among physically active women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A history of GDM was associated with a greater risk of incident dementia. Type 2 diabetes partially mediated this relationship. Strategies for dementia prevention might be considered for women with a history of GDM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"295 6","pages":"774-784"},"PeriodicalIF":11.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140612223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}