European Journal of Clinical Investigation最新文献_第10页

Body temperature, systemic inflammation and risk of adverse events in patients with acute coronary syndromes 急性冠状动脉综合征患者的体温、全身炎症和不良事件风险。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-09-30 DOI: 10.1111/eci.14314

Jan Gerrit van der Stouwe, Konstantin Godly, Simon Kraler, Julia Godly, Christian M. Matter, Florian A. Wenzl, Arnold von Eckardstein, Lorenz Räber, François Mach, Slayman Obeid, Christian Templin, Thomas F. Lüscher, David Niederseer, the SPUM-ACS investigators

Background

Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS.

Methods

From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE-ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin-T (hs-cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni- and multivariable regression models were fit to assess associations of BT with future MACE risk.

Results

Among patients with STEMI, BT was not predictive of 1-year MACE, but a U-shaped relationship between BT and MACE risk was noted in those with NSTE-ACS (p = .029), translating into a 2.4-fold (HR, 2.44, 95% CI, 1.16–5.16) increased 1-year MACE risk in those with BT >36.8°C (reference: 36.6–36.8°C). Results remained robust in multivariable-adjusted analyses accounting for sex, age, diabetes, renal function and hs-cTnT. However, when introducing hs-CRP, the BT-MACE association did not prevail.

Conclusions

In prospectively recruited patients with ACS, initial BT shows a U-shaped relationship with 1-year MACE risk among those with NSTE-ACS, but not in those with STEMI. BT is a broadly available low-cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti-inflammatory intervention.

Registration

ClinicalTrials.gov Identifier: NCT01000701.

背景：炎症过程可诱发急性冠状动脉综合征（ACS），这可能导致核心体温（BT）升高，而核心体温是一种广泛使用的低成本全身炎症标志物。在此，我们旨在根据初始 BT 划分 ST 段抬高型心肌梗死（STEMI）和非 ST 段抬高型 ACS（NSTE-ACS）患者的基线特征，并评估其对指数 ACS 后主要不良心血管事件（MACE）的预测作用：从2012年到2017年，苏黎世大学医院共招募了1044名ACS患者，其中517名为STEMI患者，527名为NSTE-ACS患者。在冠状动脉造影术前，通过数字耳温计测量BT以及高敏C反应蛋白（hs-CRP）和心肌肌钙蛋白-T（hs-cTnT）水平。根据初始BT对患者进行分层，并拟合单变量和多变量回归模型以评估BT与未来MACE风险的关系：在 STEMI 患者中，BT 对 1 年 MACE 没有预测作用，但在 NSTE-ACS 患者中，BT 与 MACE 风险呈 U 型关系（p = 0.029），即 BT >36.8°C 的患者 1 年 MACE 风险增加 2.4 倍（HR，2.44，95% CI，1.16-5.16）（参考值：36.6-36.8°C）。在考虑性别、年龄、糖尿病、肾功能和 hs-cTnT 的多变量调整分析中，结果依然稳健。然而，当引入hs-CRP时，BT与MACE的关系并不占优势：在前瞻性招募的 ACS 患者中，初始 BT 与 NSTE-ACS 患者的 1 年 MACE 风险呈 U 型关系，但与 STEMI 患者无关。BT是一种可广泛使用的低成本标记物，可用于识别炎症负担重、复发缺血性事件风险高的ACS患者，因此可能适合进行抗炎干预：注册：ClinicalTrials.gov Identifier：注册：ClinicalTrials.gov Identifier：NCT01000701。

{"title":"Body temperature, systemic inflammation and risk of adverse events in patients with acute coronary syndromes","authors":"Jan Gerrit van der Stouwe, Konstantin Godly, Simon Kraler, Julia Godly, Christian M. Matter, Florian A. Wenzl, Arnold von Eckardstein, Lorenz Räber, François Mach, Slayman Obeid, Christian Templin, Thomas F. Lüscher, David Niederseer, the SPUM-ACS investigators","doi":"10.1111/eci.14314","DOIUrl":"10.1111/eci.14314","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE-ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin-T (hs-cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni- and multivariable regression models were fit to assess associations of BT with future MACE risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among patients with STEMI, BT was not predictive of 1-year MACE, but a <i>U</i>-shaped relationship between BT and MACE risk was noted in those with NSTE-ACS (<i>p</i> = .029), translating into a 2.4-fold (HR, 2.44, 95% CI, 1.16–5.16) increased 1-year MACE risk in those with BT >36.8°C (reference: 36.6–36.8°C). Results remained robust in multivariable-adjusted analyses accounting for sex, age, diabetes, renal function and hs-cTnT. However, when introducing hs-CRP, the BT-MACE association did not prevail.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In prospectively recruited patients with ACS, initial BT shows a <i>U</i>-shaped relationship with 1-year MACE risk among those with NSTE-ACS, but not in those with STEMI. BT is a broadly available low-cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti-inflammatory intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov Identifier: NCT01000701.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A weekly 4-methylpyrazole treatment attenuates the development of non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) in male mice: Role of JNK 每周一次的4-甲基吡唑治疗可减轻雄性小鼠非肥胖代谢功能障碍相关性脂肪性肝病（MASLD）的发展：JNK的作用

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-09-29 DOI: 10.1111/eci.14320

Katharina Burger, Finn Jung, Raphaela Staltner, Katja Csarmann, Kerstin Schweiger, Annette Brandt, Anja Baumann, Julia Scholda, Florian Kopp, Ina Bergheim

Background

4-methylpyrazole (4MP, fomepizole) is a competitive inhibitor of alcohol dehydrogenase (ADH) preventing the metabolism of ethylene glycol and methanol, respectively, into their toxic metabolites. 4MP seems also to possess a potential in the treatment of intoxication from other substance, for example, acetaminophen, and to modulate JNK-dependent signalling. Here, we determined if a treatment with 4MP once weekly affects the development of diet-induced non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) in C57BL/6 mice.

Methods

Male C57BL/6 mice (6–8 weeks old, n = 7-8/group) were pair-fed either a liquid control diet (C) or a liquid sucrose-, fat- and cholesterol-rich diet (SFC) for 8 weeks while being concomitantly treated with 4MP (50 mg/kg bw i.p.) or vehicle once a week. Liver damage, inflammatory markers and glucose tolerance were assessed. Moreover, in endotoxin-challenged J774A.1 cells pretreated with 4MP, pro-inflammatory markers were assessed.

Results

The concomitant treatment of SFC-fed mice with 4MP attenuated the increase in JNK phosphorylation and pro-inflammatory markers like IFNγ, IL-6 and 3-nitrotyrosine protein adducts in liver tissue found in vehicle-treated SFC-fed mice, while not affecting impairments of glucose tolerance or the increase in portal endotoxin levels. Moreover, a pretreatment of endotoxin-stimulated J774A.1 cells with 4MP significantly attenuated the increases in JNK phosphorylation and pro-inflammatory mediators like IL-6 and Mcp1.

Conclusions

Taken together, our results suggest that a treatment with 4MP once weekly attenuates the activation of JNK and dampens the development of non-obese MASLD in mice.

背景：4-甲基吡唑（4MP，fomepizole）是乙醇脱氢酶（ADH）的竞争性抑制剂，可阻止乙二醇和甲醇分别代谢为有毒的代谢物。4MP 似乎还具有治疗其他物质（如对乙酰氨基酚）中毒的潜力，并能调节依赖于 JNK 的信号传导。在此，我们确定了每周一次使用 4MP 是否会影响 C57BL/6 小鼠饮食诱导的非肥胖代谢功能障碍相关性脂肪性肝病（MASLD）的发展：雄性 C57BL/6 小鼠（6-8 周大，n = 7-8/组）配对饲喂流质对照饮食（C）或富含蔗糖、脂肪和胆固醇的流质饮食（SFC）8 周，同时每周一次接受 4MP （50 毫克/千克体重，i.p. ）或药物治疗。对肝损伤、炎症指标和葡萄糖耐量进行了评估。此外，还评估了用 4MP 预处理的内毒素挑战 J774A.1 细胞的促炎标记物：结果：同时用 4MP 处理 SFC 饲养的小鼠可减轻车辆处理的 SFC 饲养小鼠肝组织中 JNK 磷酸化和 IFNγ、IL-6、3-硝基酪氨酸蛋白加合物等促炎标记物的增加，但不会影响葡萄糖耐量的损害或门静脉内毒素水平的增加。此外，用 4MP 对内毒素刺激的 J774A.1 细胞进行预处理，可显著减轻 JNK 磷酸化以及 IL-6 和 Mcp1 等促炎介质的增加：综上所述，我们的研究结果表明，每周使用一次 4MP 可减轻 JNK 的活化，并抑制小鼠非肥胖性 MASLD 的发展。

{"title":"A weekly 4-methylpyrazole treatment attenuates the development of non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) in male mice: Role of JNK","authors":"Katharina Burger, Finn Jung, Raphaela Staltner, Katja Csarmann, Kerstin Schweiger, Annette Brandt, Anja Baumann, Julia Scholda, Florian Kopp, Ina Bergheim","doi":"10.1111/eci.14320","DOIUrl":"10.1111/eci.14320","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>4-methylpyrazole (4MP, fomepizole) is a competitive inhibitor of alcohol dehydrogenase (ADH) preventing the metabolism of ethylene glycol and methanol, respectively, into their toxic metabolites. 4MP seems also to possess a potential in the treatment of intoxication from other substance, for example, acetaminophen, and to modulate JNK-dependent signalling. Here, we determined if a treatment with 4MP once weekly affects the development of diet-induced non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) in C57BL/6 mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male C57BL/6 mice (6–8 weeks old, <i>n</i> = 7-8/group) were pair-fed either a liquid control diet (C) or a liquid sucrose-, fat- and cholesterol-rich diet (SFC) for 8 weeks while being concomitantly treated with 4MP (50 mg/kg bw i.p.) or vehicle once a week. Liver damage, inflammatory markers and glucose tolerance were assessed. Moreover, in endotoxin-challenged J774A.1 cells pretreated with 4MP, pro-inflammatory markers were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The concomitant treatment of SFC-fed mice with 4MP attenuated the increase in JNK phosphorylation and pro-inflammatory markers like IFNγ, IL-6 and 3-nitrotyrosine protein adducts in liver tissue found in vehicle-treated SFC-fed mice, while not affecting impairments of glucose tolerance or the increase in portal endotoxin levels. Moreover, a pretreatment of endotoxin-stimulated J774A.1 cells with 4MP significantly attenuated the increases in JNK phosphorylation and pro-inflammatory mediators like IL-6 and <i>Mcp1</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Taken together, our results suggest that a treatment with 4MP once weekly attenuates the activation of JNK and dampens the development of non-obese MASLD in mice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lung damage in SARS-CoV-2 patients: An autopsy study in the era of vaccination SARS-CoV-2 患者的肺部损伤：疫苗接种时代的尸检研究。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-09-29 DOI: 10.1111/eci.14325

Rossana Bussani, Aldostefano Porcari, Maurizio Pinamonti, Anthea Iacobucci, Eleonora Belladonna, Ariella Tomasini, Fabrizio Zanconati, Chiara Collesi, Mauro Giacca, Giorgio Berlot, Gianfranco Sinagra, Furio Silvestri

Aims

The contribution of SARS-CoV-2 infection on lung damage and the effect of vaccination on either containing the number of deaths or mitigating lung damage has not been systematically investigated.

Methods

Post-mortem analysis was performed among consecutive in-patients with COVID-19 deceased in the Province of Trieste (2020–2022). The outcomes of the study were (i) rates of in-hospital mortality, (ii) contribution of COVID-19 to death, (iii) histological extent of lung injury and (iv) impact of vaccination.

Results

A total of 1038 consecutive hospitalized patients who died with SARS-CoV-2 infection were autopsied and deep histological analysis of the lungs was performed in a randomly selected sample of 508 cases. Among them, SARS-CoV-2 infection was (a) the cause of death (n = 90), (b) contributing to death (n = 304) and (c) an accompanying feature (n = 114). The incidence of SARS-CoV-2 infection as the primary cause of mortality decreased over time (23.8% in 2020, 20.9% in 2021 and 7.9% in 2022). On multivariable analysis, vaccination (any dose) was independently associated with lower rates of death related to SARS-CoV-2 infection (HR .15, p < .001), after adjusting for other independent predictors. A total of 172 patients were vaccinated at least with two doses at the time of death: 93% triple-vaccinated, 7% double-vaccinated. On histological analysis, vaccinated patients had a greater frequency of pneumonia severity score 0 and 1 (20.3% vs. 5.4% and 20.9% vs. 7.7%, p < .001, respectively), and a substantially lower proportion of pneumonia severity score 3 (26.2% vs. 55.1%, p < .001) compared to unvaccinated patients.

Conclusions

COVID-19 vaccination has substantially reduced rates of death related to SARS-CoV-2 infection over time and may have the ability to mitigate lung damage.

目的：SARS-CoV-2 感染对肺损伤的影响以及接种疫苗对控制死亡人数或减轻肺损伤的效果尚未进行系统研究：对的里雅斯特省（2020-2022 年）连续死亡的 COVID-19 住院病人进行了尸检分析。研究结果包括：(i) 院内死亡率；(ii) COVID-19 对死亡的影响；(iii) 肺损伤的组织学程度；(iv) 接种疫苗的影响：共对 1038 名因感染 SARS-CoV-2 而死亡的连续住院患者进行了尸检，并对随机抽取的 508 例患者的肺部进行了深度组织学分析。其中，SARS-CoV-2 感染是（a）死亡原因（90 例），（b）死亡诱因（304 例）和（c）伴随特征（114 例）。作为主要死因的 SARS-CoV-2 感染率随着时间的推移而下降（2020 年为 23.8%，2021 年为 20.9%，2022 年为 7.9%）。在多变量分析中，接种疫苗（任何剂量）与较低的 SARS-CoV-2 感染相关死亡率有独立联系（HR .15，p 结论：接种 COVID-19 疫苗大大降低了 SARS-CoV-2 感染的死亡率：随着时间的推移，接种 COVID-19 疫苗大大降低了与 SARS-CoV-2 感染相关的死亡率，并有可能减轻肺损伤。

{"title":"Lung damage in SARS-CoV-2 patients: An autopsy study in the era of vaccination","authors":"Rossana Bussani, Aldostefano Porcari, Maurizio Pinamonti, Anthea Iacobucci, Eleonora Belladonna, Ariella Tomasini, Fabrizio Zanconati, Chiara Collesi, Mauro Giacca, Giorgio Berlot, Gianfranco Sinagra, Furio Silvestri","doi":"10.1111/eci.14325","DOIUrl":"10.1111/eci.14325","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The contribution of SARS-CoV-2 infection on lung damage and the effect of vaccination on either containing the number of deaths or mitigating lung damage has not been systematically investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Post-mortem analysis was performed among consecutive in-patients with COVID-19 deceased in the Province of Trieste (2020–2022). The outcomes of the study were (i) rates of in-hospital mortality, (ii) contribution of COVID-19 to death, (iii) histological extent of lung injury and (iv) impact of vaccination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1038 consecutive hospitalized patients who died with SARS-CoV-2 infection were autopsied and deep histological analysis of the lungs was performed in a randomly selected sample of 508 cases. Among them, SARS-CoV-2 infection was (a) the cause of death (<i>n</i> = 90), (b) contributing to death (<i>n</i> = 304) and (c) an accompanying feature (<i>n</i> = 114). The incidence of SARS-CoV-2 infection as the primary cause of mortality decreased over time (23.8% in 2020, 20.9% in 2021 and 7.9% in 2022). On multivariable analysis, vaccination (any dose) was independently associated with lower rates of death related to SARS-CoV-2 infection (HR .15, <i>p</i> < .001), after adjusting for other independent predictors. A total of 172 patients were vaccinated at least with two doses at the time of death: 93% triple-vaccinated, 7% double-vaccinated. On histological analysis, vaccinated patients had a greater frequency of pneumonia severity score 0 and 1 (20.3% vs. 5.4% and 20.9% vs. 7.7%, <i>p</i> < .001, respectively), and a substantially lower proportion of pneumonia severity score 3 (26.2% vs. 55.1%, <i>p</i> < .001) compared to unvaccinated patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>COVID-19 vaccination has substantially reduced rates of death related to SARS-CoV-2 infection over time and may have the ability to mitigate lung damage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dose-dependent association between estimated glomerular filtration rate and the subsequent risk of depression: An analysis of a nationwide epidemiological dataset 估计肾小球滤过率与后续抑郁风险之间的剂量依赖关系：全国流行病学数据集分析。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-09-27 DOI: 10.1111/eci.14322

Toshiyuki Ko, Hidehiro Kaneko, Yuta Suzuki, Akira Okada, Tatsuhiko Azegami, Katsuhito Fujiu, Norifumi Takeda, Hiroyuki Morita, Takashi Yokoo, Kaori Hayashi, Issei Komuro, Hideo Yasunaga, Masaomi Nangaku, Norihiko Takeda

Background

Although the risk of depression is well-known in the patients with kidney dysfunction, especially at the late stages, little is known about the exact point at which the decline in estimated glomerular filtration rate (eGFR) begins to significantly increase the risk of depression. In the present study, we analysed a nationwide epidemiological dataset to investigate the dose-dependent association between baseline eGFR and a future risk of developing depression in a general population.

Methods

We retrospectively analysed 1,518,885 individuals (male: 46.3%) without a history of depression identified between April 2014 and November 2022 within a nationwide epidemiological database, provided by DeSC Healthcare (Tokyo, Japan). We investigated the association of eGFR with the incidence of depression using Cox regression analyses and also conducted cubic spline analysis to investigate the dose-dependent association between eGFR and depression.

Results

In the mean follow-up of 1218 ± 693 days, 45,878 cases (3.0% for total participants, 2.6% for men and 3.3% for women) of depression were recorded. The risk of depression increased with the eGFR decline as well as the presence of proteinuria. Multivariable Cox regression analysis showed the hazard ratio (95% CI) of depression in each kidney function category (eGFR ≥90, 60–89, 45–59, 30–44, 15–29, and < 15 mL/min/1.73 m²) was 1.14 (1.11–1.17), 1 (reference), 1.11 (1.08–1.14), 1.51 (1.43–1.59), 1.77 (1.57–1.99) and 1.77 (1.26–2.50), respectively. In the cubic spline analysis, the risk of depression continued to increase monotonically as the eGFR declined when the eGFR fell below approximately 65 mL/min/1.73 m².

Conclusions

Our analysis using a large-scale epidemiological dataset presented the dose-dependent association between eGFR decline and the risk of depression, which highlights the importance of incorporating mental health assessments into the routine care of patients with kidney dysfunction, regardless of the stage of their disease.

背景：尽管众所周知肾功能不全患者有患抑郁症的风险，尤其是在晚期，但人们对估计肾小球滤过率（eGFR）下降开始显著增加抑郁症风险的确切时间点知之甚少。在本研究中，我们分析了一个全国性的流行病学数据集，以调查基线 eGFR 与普通人群未来患抑郁症风险之间的剂量依赖关系：我们回顾性分析了由DeSC Healthcare（日本东京）提供的全国流行病学数据库中2014年4月至2022年11月期间发现的1,518,885名无抑郁症病史者（男性：46.3%）。我们利用 Cox 回归分析研究了 eGFR 与抑郁症发病率之间的关系，还进行了立方样条分析，以研究 eGFR 与抑郁症之间的剂量依赖关系：结果：在平均为 1218 ± 693 天的随访中，共记录了 45,878 例抑郁症病例（占所有参与者的 3.0%，男性为 2.6%，女性为 3.3%）。抑郁的风险随着 eGFR 的下降和蛋白尿的出现而增加。多变量考克斯回归分析显示，各肾功能类别（eGFR ≥90、60-89、45-59、30-44、15-29 和 2）的抑郁危险比（95% CI）分别为 1.14（1.11-1.17）、1（参考）、1.11（1.08-1.14）、1.51（1.43-1.59）、1.77（1.57-1.99）和 1.77（1.26-2.50）。在立方样条分析中，当 eGFR 低于约 65 mL/min/1.73 m2 时，抑郁风险随着 eGFR 的下降而单调上升：我们利用大规模流行病学数据集进行的分析表明，eGFR 下降与抑郁风险之间存在剂量依赖关系，这凸显了将心理健康评估纳入肾功能不全患者日常护理的重要性，无论患者处于哪个疾病阶段。

{"title":"Dose-dependent association between estimated glomerular filtration rate and the subsequent risk of depression: An analysis of a nationwide epidemiological dataset","authors":"Toshiyuki Ko, Hidehiro Kaneko, Yuta Suzuki, Akira Okada, Tatsuhiko Azegami, Katsuhito Fujiu, Norifumi Takeda, Hiroyuki Morita, Takashi Yokoo, Kaori Hayashi, Issei Komuro, Hideo Yasunaga, Masaomi Nangaku, Norihiko Takeda","doi":"10.1111/eci.14322","DOIUrl":"10.1111/eci.14322","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although the risk of depression is well-known in the patients with kidney dysfunction, especially at the late stages, little is known about the exact point at which the decline in estimated glomerular filtration rate (eGFR) begins to significantly increase the risk of depression. In the present study, we analysed a nationwide epidemiological dataset to investigate the dose-dependent association between baseline eGFR and a future risk of developing depression in a general population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analysed 1,518,885 individuals (male: 46.3%) without a history of depression identified between April 2014 and November 2022 within a nationwide epidemiological database, provided by DeSC Healthcare (Tokyo, Japan). We investigated the association of eGFR with the incidence of depression using Cox regression analyses and also conducted cubic spline analysis to investigate the dose-dependent association between eGFR and depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the mean follow-up of 1218 ± 693 days, 45,878 cases (3.0% for total participants, 2.6% for men and 3.3% for women) of depression were recorded. The risk of depression increased with the eGFR decline as well as the presence of proteinuria. Multivariable Cox regression analysis showed the hazard ratio (95% CI) of depression in each kidney function category (eGFR ≥90, 60–89, 45–59, 30–44, 15–29, and < 15 mL/min/1.73 m<sup>2</sup>) was 1.14 (1.11–1.17), 1 (reference), 1.11 (1.08–1.14), 1.51 (1.43–1.59), 1.77 (1.57–1.99) and 1.77 (1.26–2.50), respectively. In the cubic spline analysis, the risk of depression continued to increase monotonically as the eGFR declined when the eGFR fell below approximately 65 mL/min/1.73 m<sup>2</sup>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our analysis using a large-scale epidemiological dataset presented the dose-dependent association between eGFR decline and the risk of depression, which highlights the importance of incorporating mental health assessments into the routine care of patients with kidney dysfunction, regardless of the stage of their disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the intricacies of chronic kidney disease: From ocular manifestations to therapeutic frontiers 揭开慢性肾脏病的神秘面纱：从眼部表现到治疗前沿。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-09-26 DOI: 10.1111/eci.14324

Mehmet Kanbay, Mustafa Guldan, Lasin Ozbek, Sidar Copur, Francesca Mallamaci, Carmine Zoccali

Background

Shared anatomical, histological and physiological pathways between the kidney and the eye are well documented, demonstrating that ocular manifestations serve as valuable prognostic indicators in chronic kidney disease (CKD), providing insights into disease severity and progression. Through non-invasive imaging modalities such as retinal fundus photography, early retinal microvascular alterations indicative of CKD progression can be detected, enabling timely intervention and risk stratification. However, the conclusions drawn from the review primarily demonstrate a strong or independent association between glaucoma or retinopathy and CKD.

Results and Conclusion

Multiple shared pathophysiological events have been implicated in the pathogenesis in the alterations at eye and kidney including renin-angiotensin-aldosterone system. Patients with CKD are more likely to experience glaucoma, age-related macular degeneration, cataracts, uremic optic neuropathy and retinopathy. To establish the role of ocular manifestations in predicting CKD progression, it is crucial to address the limitations of correlation and explore the underlying causality with further research on common disease pathogenesis. Additionally, specific methods for risk stratification based on retinal changes, the effectiveness of timely interventions, and the development of predictive tools combining ocular and renal data are of utmost importance research topics to enlighten the bidirectional causality.

背景：肾脏和眼睛之间共同的解剖学、组织学和生理学途径已被充分记录，这表明眼部表现是慢性肾脏病（CKD）有价值的预后指标，可帮助了解疾病的严重程度和进展情况。通过视网膜眼底照相等非侵入性成像模式，可以检测到表明 CKD 进展的早期视网膜微血管改变，从而进行及时干预和风险分层。然而，综述得出的结论主要表明青光眼或视网膜病变与 CKD 之间存在密切或独立的关联：包括肾素-血管紧张素-醛固酮系统在内的多种共同的病理生理事件被认为与眼肾改变的发病机制有关。慢性肾脏病患者更容易患青光眼、老年性黄斑变性、白内障、尿毒症视神经病变和视网膜病变。要确定眼部表现在预测慢性肾脏病进展中的作用，关键是要解决相关性的局限性，并通过对常见疾病发病机制的进一步研究来探索潜在的因果关系。此外，根据视网膜变化进行风险分层的具体方法、及时干预的有效性以及结合眼部和肾脏数据的预测工具的开发，都是揭示双向因果关系最重要的研究课题。

{"title":"Unveiling the intricacies of chronic kidney disease: From ocular manifestations to therapeutic frontiers","authors":"Mehmet Kanbay, Mustafa Guldan, Lasin Ozbek, Sidar Copur, Francesca Mallamaci, Carmine Zoccali","doi":"10.1111/eci.14324","DOIUrl":"10.1111/eci.14324","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Shared anatomical, histological and physiological pathways between the kidney and the eye are well documented, demonstrating that ocular manifestations serve as valuable prognostic indicators in chronic kidney disease (CKD), providing insights into disease severity and progression. Through non-invasive imaging modalities such as retinal fundus photography, early retinal microvascular alterations indicative of CKD progression can be detected, enabling timely intervention and risk stratification. However, the conclusions drawn from the review primarily demonstrate a strong or independent association between glaucoma or retinopathy and CKD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusion</h3>\u0000 \u0000 <p>Multiple shared pathophysiological events have been implicated in the pathogenesis in the alterations at eye and kidney including renin-angiotensin-aldosterone system. Patients with CKD are more likely to experience glaucoma, age-related macular degeneration, cataracts, uremic optic neuropathy and retinopathy. To establish the role of ocular manifestations in predicting CKD progression, it is crucial to address the limitations of correlation and explore the underlying causality with further research on common disease pathogenesis. Additionally, specific methods for risk stratification based on retinal changes, the effectiveness of timely interventions, and the development of predictive tools combining ocular and renal data are of utmost importance research topics to enlighten the bidirectional causality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adrenergic dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and meta-analysis 肌痛性脑脊髓炎/慢性疲劳综合征和纤维肌痛患者的肾上腺素能功能障碍：系统回顾和荟萃分析。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-09-25 DOI: 10.1111/eci.14318

Jolien Hendrix, Lara Fanning, Arne Wyns, Ishtiaq Ahmed, Madhura Shekhar Patil, Emma Richter, Jente Van Campenhout, Kelly Ickmans, Rembert Mertens, Jo Nijs, Lode Godderis, Andrea Polli

Background

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are comorbid disorders with overlapping symptoms. Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME/CFS and FM aiming to identify targetable pathophysiological mechanisms.

Methods

A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME/CFS or FM compared to healthy controls at baseline were included. Meta-analyses were performed using R statistical software.

Results

This meta-analysis of 37 studies, encompassing 543 ME/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD = .49 [.31–.67]; Z = 5.29, p < .01) and β1 adrenergic receptor expression (SMD = .79 [.06–1.52]; Z = 2.13; p = .03) in blood of ME/CFS patients at rest. Additionally, patients with ME/CFS had a greater increase in the expression of α2A adrenergic receptor (AR, SMD = .57 [.18–.97]; Z = 2.85, p < .01), β2 AR (SMD = .41 [.02–.81]; Z = 2.04; p = .04) and COMT (SMD = .42 [.03–.81]; Z = 2.11; p = .03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD = .11 [−.47 to −.70]; Z = 2.10; p = .04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD = −.79 [−1.27 to −.30]; Z = −3.14; p < .01).

Conclusion

This systematic review and meta-analysis revealed adrenergic dysfunction mainly in patients with ME/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME/CFS rather than FM.

背景：肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）和纤维肌痛（FM）是症状重叠的合并症。与健康人相比，研究强调自律神经功能失调，尤其是涉及交感神经分支的自律神经功能失调。过去的综述侧重于神经生理学评估，而本系统性综述则总结了生物肾上腺素能标记物，对在 ME/CFS 和 FM 中观察到的交感神经功能障碍提供了更深入的见解，旨在确定可针对的病理生理机制：方法：在 PubMed、Web of Science、Embase 和 Scopus 上进行了系统检索。方法：在PubM、Web Science、Embase和Scopus上进行了系统搜索，纳入了调查ME/CFS或FM患者与基线健康对照组相比肾上腺素能功能的外周生物标志物的研究。使用R统计软件进行荟萃分析：该荟萃分析共纳入 37 项研究，包括 543 名 ME/CFS 患者和 651 名 FM 患者，分别与 747 名和 447 名健康对照者进行比较，结果显示肾上腺素升高（SMD = .49 [.31-.67]; Z = 5.29, p 结论：该荟萃分析发现，ME/CFS 患者和 FM 患者的肾上腺素功能与健康对照者存在显著差异：该系统综述和荟萃分析显示，肾上腺素功能障碍主要发生在 ME/CFS 患者身上。ME/CFS患者较高的肾上腺素基线水平和对运动的非典型反应表明，肾上腺素能异常所凸显的交感神经功能障碍在ME/CFS而非FM的病理生理学中占更大比重。

{"title":"Adrenergic dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and meta-analysis","authors":"Jolien Hendrix, Lara Fanning, Arne Wyns, Ishtiaq Ahmed, Madhura Shekhar Patil, Emma Richter, Jente Van Campenhout, Kelly Ickmans, Rembert Mertens, Jo Nijs, Lode Godderis, Andrea Polli","doi":"10.1111/eci.14318","DOIUrl":"10.1111/eci.14318","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are comorbid disorders with overlapping symptoms. Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME/CFS and FM aiming to identify targetable pathophysiological mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME/CFS or FM compared to healthy controls at baseline were included. Meta-analyses were performed using R statistical software.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This meta-analysis of 37 studies, encompassing 543 ME/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD = .49 [.31–.67]; <i>Z</i> = 5.29, <i>p</i> < .01) and β1 adrenergic receptor expression (SMD = .79 [.06–1.52]; <i>Z</i> = 2.13; <i>p</i> = .03) in blood of ME/CFS patients at rest. Additionally, patients with ME/CFS had a greater increase in the expression of α2A adrenergic receptor (AR, SMD = .57 [.18–.97]; <i>Z</i> = 2.85, <i>p</i> < .01), β2 AR (SMD = .41 [.02–.81]; <i>Z</i> = 2.04; <i>p</i> = .04) and COMT (SMD = .42 [.03–.81]; <i>Z</i> = 2.11; <i>p</i> = .03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD = .11 [−.47 to −.70]; <i>Z</i> = 2.10; <i>p</i> = .04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD = −.79 [−1.27 to −.30]; <i>Z</i> = −3.14; <i>p</i> < .01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This systematic review and meta-analysis revealed adrenergic dysfunction mainly in patients with ME/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME/CFS rather than FM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long-term cognitive function changes with non-vitamin K oral anticoagulants in older patients with atrial fibrillation. A multicenter cohort study 老年心房颤动患者服用非维生素 K 口服抗凝剂后认知功能的长期变化。一项多中心队列研究。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-09-23 DOI: 10.1111/eci.14321

Giuseppe Armentaro, Graziella D'Arrigo, Daniele Pastori, Giulia Crudo, Mario Daidone, Luca Soraci, Carlo Alberto Pastura, Marcello Divino, Annalisa Pitino, Mercedes Gori, Giovanni Tripepi, Egidio Imbalzano, Andrea Corsonello, Pasquale Pignatelli, Francesco Andreozzi, Antonino Tuttolomondo, Angela Sciacqua

Background

Atrial fibrillation is associated with several comorbidities, particularly cognitive impairment and dementia, especially in older patients. Non-vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) were used to prevent thromboembolic events. However, data on the real benefit of these drugs on cognitive function decline remains controversial. In this study we evaluated the effect of NOACs compared to VKAs on the absolute and relative decline in cognitive function over time.

Methods

Nine hundred and eighty-three older patients with nonvalvular AF were enrolled (76 ± 6 years; 291 on VKAs and 692 on NOACs). The cognitive function was assessed with Mini Mental State examination (MMSE) score. The between-arms difference of cognitive evolution over time was investigated by Linear Mixed Models and group-based trajectory model analyses.

Results

In the whole multicenter observational study, after a long follow-up of 7.2 ± 3.4 years, the patients of the NOACs versus VKAs group had lowest absolute reduction of the MMSE score between baseline and follow-up (−0.3 ± 0.03 vs.−1.7 ± 0.1, p < 0.001). After stratification into five subgroups according to trajectories of MMSE score over time, the probability to belong to trajectories with lower decline in cognitive functions was higher in patients on NOACs than in those on VKAs (3.93–13.88 times).

Conclusion

In older patients with atrial fibrillation, the use of NOACs was associated with a smaller decline of cognitive function over time compared to the VKAs, regardless that patients in the NOACs group were older and with a higher burden of comorbidities.

背景：心房颤动与多种合并症有关，特别是认知障碍和痴呆，尤其是在老年患者中。非维生素 K 口服抗凝剂（NOACs）或维生素 K 拮抗剂（VKAs）被用于预防血栓栓塞事件。然而，关于这些药物对认知功能下降的真正益处的数据仍存在争议。在这项研究中，我们评估了 NOAC 与 VKAs 相比对认知功能随时间的绝对和相对下降的影响：共纳入 983 名老年非瓣膜性房颤患者（76 ± 6 岁；291 人服用 VKA，692 人服用 NOAC）。认知功能通过迷你精神状态检查（MMSE）评分进行评估。通过线性混合模型和基于组别的轨迹模型分析，研究了各组间认知功能随时间演变的差异：在整个多中心观察研究中，经过 7.2 ± 3.4 年的长期随访，NOACs 组与 VKAs 组患者的 MMSE 评分在基线与随访之间的绝对值降幅最小（-0.3 ± 0.03 vs.-1.7 ± 0.1，P 结论：NOACs 组与 VKAs 组患者的 MMSE 评分在基线与随访之间的绝对值降幅最小：在老年心房颤动患者中，使用 NOACs 与 VKAs 相比，随着时间的推移，认知功能的下降幅度较小，尽管 NOACs 组患者年龄较大，合并症较多。

{"title":"Long-term cognitive function changes with non-vitamin K oral anticoagulants in older patients with atrial fibrillation. A multicenter cohort study","authors":"Giuseppe Armentaro, Graziella D'Arrigo, Daniele Pastori, Giulia Crudo, Mario Daidone, Luca Soraci, Carlo Alberto Pastura, Marcello Divino, Annalisa Pitino, Mercedes Gori, Giovanni Tripepi, Egidio Imbalzano, Andrea Corsonello, Pasquale Pignatelli, Francesco Andreozzi, Antonino Tuttolomondo, Angela Sciacqua","doi":"10.1111/eci.14321","DOIUrl":"10.1111/eci.14321","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Atrial fibrillation is associated with several comorbidities, particularly cognitive impairment and dementia, especially in older patients. Non-vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) were used to prevent thromboembolic events. However, data on the real benefit of these drugs on cognitive function decline remains controversial. In this study we evaluated the effect of NOACs compared to VKAs on the absolute and relative decline in cognitive function over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nine hundred and eighty-three older patients with nonvalvular AF were enrolled (76 ± 6 years; 291 on VKAs and 692 on NOACs). The cognitive function was assessed with Mini Mental State examination (MMSE) score. The between-arms difference of cognitive evolution over time was investigated by Linear Mixed Models and group-based trajectory model analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the whole multicenter observational study, after a long follow-up of 7.2 ± 3.4 years, the patients of the NOACs versus VKAs group had lowest absolute reduction of the MMSE score between baseline and follow-up (−0.3 ± 0.03 vs.−1.7 ± 0.1, <i>p</i> < 0.001). After stratification into five subgroups according to trajectories of MMSE score over time, the probability to belong to trajectories with lower decline in cognitive functions was higher in patients on NOACs than in those on VKAs (3.93–13.88 times).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In older patients with atrial fibrillation, the use of NOACs was associated with a smaller decline of cognitive function over time compared to the VKAs, regardless that patients in the NOACs group were older and with a higher burden of comorbidities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neurovascular dysfunction in psychiatric disorders: Underlying mechanisms and therapeutic approaches 精神疾病中的神经血管功能障碍：基本机制和治疗方法。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-09-23 DOI: 10.1111/eci.14319

Eliane Swely Sanches, Daniela Simões, Filipa Isabel Baptista, Ana Paula Silva

Background

Neurovascular interfaces, specifically the blood–brain barrier (BBB) and blood–retinal barrier (BRB), play pivotal roles in maintaining the homeostasis of the central nervous system (CNS). For a long time, these structures were seen only as a way of protection, but we currently know that they have a critical role in CNS (dys)function. Several studies have identified neurovascular alterations in early stages of brain and eye diseases, contributing to the pathophysiology of such conditions. More recently, interesting data have also highlighted the importance of neurovasculature in psychiatric disorders.

Methods

Using the PubMed database, we brought together the evidence concerning the changes in BBB and BRB under psychiatric conditions, with a focus on anxiety, major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD) and drug abuse, specifically related with methamphetamine (METH) and cocaine consumption.

Results

We summarized the main findings obtained from in vitro and animal studies, as well as clinical research that has been undertaken to identify neurovascular abnormalities upon such neuropsychiatric disorders. The drivers of barrier alterations were examined, namely the role of neuroinflammation, while reporting putative barrier-associated biomarkers of these disorders.

Conclusion

This review underscores the critical need for a deeper understanding of BBB and BRB function in neuropsychiatric conditions and their potential as therapeutic targets while elucidating the key players involved. The innovative approaches to managing these complex disorders are also addressed while bridging the gap concerning what is currently known regarding the association between neuropsychiatric conditions and their vascular implications.

背景：神经血管界面，特别是血脑屏障（BBB）和血视网膜屏障（BRB），在维持中枢神经系统（CNS）平衡方面发挥着关键作用。长期以来，这些结构只被视为一种保护方式，但我们现在知道，它们在中枢神经系统（功能障碍）中发挥着至关重要的作用。一些研究发现，神经血管在脑部和眼部疾病的早期阶段发生了改变，从而导致了这些疾病的病理生理学。最近，一些有趣的数据也强调了神经血管在精神疾病中的重要性：方法：我们利用 PubMed 数据库汇集了有关精神疾病情况下 BBB 和 BRB 变化的证据，重点关注焦虑症、重度抑郁症（MDD）、注意力缺陷/多动症（ADHD）和药物滥用，特别是与甲基苯丙胺（METH）和可卡因消费有关的情况：我们总结了体外研究、动物研究以及临床研究的主要发现，这些研究都是为了确定此类神经精神疾病的神经血管异常。我们研究了屏障改变的驱动因素，即神经炎症的作用，同时报告了这些疾病的屏障相关生物标志物：这篇综述强调了深入了解神经精神疾病中生物屏障和神经屏障功能的迫切需要，以及它们作为治疗靶点的潜力，同时阐明了其中的关键参与者。该综述还探讨了治疗这些复杂疾病的创新方法，同时弥补了目前对神经精神疾病及其血管影响之间关联的认识差距。

{"title":"Neurovascular dysfunction in psychiatric disorders: Underlying mechanisms and therapeutic approaches","authors":"Eliane Swely Sanches, Daniela Simões, Filipa Isabel Baptista, Ana Paula Silva","doi":"10.1111/eci.14319","DOIUrl":"10.1111/eci.14319","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neurovascular interfaces, specifically the blood–brain barrier (BBB) and blood–retinal barrier (BRB), play pivotal roles in maintaining the homeostasis of the central nervous system (CNS). For a long time, these structures were seen only as a way of protection, but we currently know that they have a critical role in CNS (dys)function. Several studies have identified neurovascular alterations in early stages of brain and eye diseases, contributing to the pathophysiology of such conditions. More recently, interesting data have also highlighted the importance of neurovasculature in psychiatric disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the PubMed database, we brought together the evidence concerning the changes in BBB and BRB under psychiatric conditions, with a focus on anxiety, major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD) and drug abuse, specifically related with methamphetamine (METH) and cocaine consumption.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We summarized the main findings obtained from in vitro and animal studies, as well as clinical research that has been undertaken to identify neurovascular abnormalities upon such neuropsychiatric disorders. The drivers of barrier alterations were examined, namely the role of neuroinflammation, while reporting putative barrier-associated biomarkers of these disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review underscores the critical need for a deeper understanding of BBB and BRB function in neuropsychiatric conditions and their potential as therapeutic targets while elucidating the key players involved. The innovative approaches to managing these complex disorders are also addressed while bridging the gap concerning what is currently known regarding the association between neuropsychiatric conditions and their vascular implications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The 1400 metabolite-mediated relationship between 91 inflammatory cytokines and migraine: An exploratory two-step Mendelian randomization study 1400 个代谢物介导的 91 种炎症细胞因子与偏头痛之间的关系：一项探索性两步孟德尔随机研究。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-09-15 DOI: 10.1111/eci.14316

Huiqi Sun, Xutong Lv, Dongbin Zhang, Yue Shen, Hongxiu Lu

Background

Inflammatory cytokines and migraines have been associated in previous research, but the underlying mechanisms of action are still elusive. The biological functions of metabolites are crucial in the onset of migraine. Our goals were to clarify the cause-and-effect connection between inflammatory cytokines and migraines and explore the potential mediating function of metabolites.

Methods

Utilizing summary-level data from genome-wide association studies (GWAS), we conducted two-sample Mendelian randomization (MR) analyses to evaluate the possible causal connection between inflammatory cytokines and migraines. A two-step MR analysis was employed to further investigate the potential mediating pathways of metabolites.

Results

MR analysis identified a total of 9 inflammatory cytokines that were genetically associated with migraines, and we subsequently identified 21 mediated relationships, with 20 metabolites (13 metabolites, 7 ratios) acting as potential mediators between 8 inflammatory cytokines and migraine. The 9 inflammatory cytokines were beta-nerve growth factor levels (β-NGF), T-cell surface glycoprotein CD5 levels (CD5), T-cell surface glycoprotein CD6 isoform levels (CD6), C-X-C motif chemokine 11 levels (CXCL11), interleukin-4 levels (IL-4), oncostatin-M levels (OSM), signalling lymphocytic activation molecule levels (SLAM), C-C motif chemokine 25 levels (CCL25) and monocyte chemoattractant protein-1 levels (MCP-1).

Conclusion

Our research findings provide evidence for both a causal connection between inflammatory cytokines and migraines, as well as a metabolite-mediated pathway. These biomarkers facilitate the detection, diagnosis and treatment of migraines while offering fresh perspectives on their underlying mechanisms.

背景：在以往的研究中，炎性细胞因子与偏头痛有关联，但其潜在的作用机制仍然难以捉摸。代谢物的生物功能对偏头痛的发病至关重要。我们的目标是阐明炎性细胞因子与偏头痛之间的因果关系，并探索代谢物的潜在中介功能：利用全基因组关联研究（GWAS）的汇总数据，我们进行了双样本孟德尔随机化（MR）分析，以评估炎性细胞因子与偏头痛之间可能存在的因果关系。为了进一步研究代谢物的潜在中介途径，我们采用了两步 MR 分析法：结果：磁共振分析共发现9种炎症细胞因子与偏头痛存在遗传相关性，随后我们又发现了21种介导关系，其中20种代谢物（13种代谢物，7种比率）是8种炎症细胞因子与偏头痛之间的潜在介导物。这 9 种炎症细胞因子分别是：β-神经生长因子水平（β-NGF）、T 细胞表面糖蛋白 CD5 水平（CD5）、T 细胞表面糖蛋白 CD6 异构体水平（CD6）、C-X-C 矩阵趋化因子 11 水平（CXCL11）、白细胞介素-4水平（IL-4）、oncostatin-M水平（OSM）、信号淋巴细胞活化分子水平（SLAM）、C-C动因趋化因子25水平（CCL25）和单核细胞趋化蛋白-1水平（MCP-1）。结论我们的研究结果为炎性细胞因子与偏头痛之间的因果关系以及代谢物介导的途径提供了证据。这些生物标志物有助于偏头痛的检测、诊断和治疗，同时为偏头痛的内在机制提供了新的视角。

{"title":"The 1400 metabolite-mediated relationship between 91 inflammatory cytokines and migraine: An exploratory two-step Mendelian randomization study","authors":"Huiqi Sun, Xutong Lv, Dongbin Zhang, Yue Shen, Hongxiu Lu","doi":"10.1111/eci.14316","DOIUrl":"10.1111/eci.14316","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inflammatory cytokines and migraines have been associated in previous research, but the underlying mechanisms of action are still elusive. The biological functions of metabolites are crucial in the onset of migraine. Our goals were to clarify the cause-and-effect connection between inflammatory cytokines and migraines and explore the potential mediating function of metabolites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Utilizing summary-level data from genome-wide association studies (GWAS), we conducted two-sample Mendelian randomization (MR) analyses to evaluate the possible causal connection between inflammatory cytokines and migraines. A two-step MR analysis was employed to further investigate the potential mediating pathways of metabolites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MR analysis identified a total of 9 inflammatory cytokines that were genetically associated with migraines, and we subsequently identified 21 mediated relationships, with 20 metabolites (13 metabolites, 7 ratios) acting as potential mediators between 8 inflammatory cytokines and migraine. The 9 inflammatory cytokines were beta-nerve growth factor levels (β-NGF), T-cell surface glycoprotein CD5 levels (CD5), T-cell surface glycoprotein CD6 isoform levels (CD6), C-X-C motif chemokine 11 levels (CXCL11), interleukin-4 levels (IL-4), oncostatin-M levels (OSM), signalling lymphocytic activation molecule levels (SLAM), C-C motif chemokine 25 levels (CCL25) and monocyte chemoattractant protein-1 levels (MCP-1).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our research findings provide evidence for both a causal connection between inflammatory cytokines and migraines, as well as a metabolite-mediated pathway. These biomarkers facilitate the detection, diagnosis and treatment of migraines while offering fresh perspectives on their underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-09-12 DOI: 10.1111/eci.14311

Laura Girardi, Marcello Di Nisio, Matteo Candeloro, Emanuele Valeriani, Walter Ageno

Background

Catheter-related thrombosis (CRT) is one of the major complications affecting patients with indwelling venous catheters, usually involving the upper extremity deep venous system. This condition can lead to potentially life-threatening complications such as pulmonary embolism and sepsis. The risk of developing CRT varies depending on type of catheters and patient characteristics. Despite advances in materials and technologies, the actual incidence of CRT is still considerable. Available evidence on CRT management remains controversial, and clinical guidelines base their recommendations on data from non-catheter related upper extremity or lower extremity deep venous thromboses.

Aims

This narrative review aims to describe the epidemiology of CRT, to review the available evidence on its management and to highlight the current unmet needs.

Methods

No formal search strategy was applied for the revision of the literature. The main sources of information used were Medline and guidelines from international societies.

Content

The management of CRT requires a careful balance between the risk of thrombus progression, recurrent events, and systemic embolization and the increased bleeding risk in often fragile patients. Open issues include the optimal management of the catheter and the type and duration of anticoagulant therapy. Direct oral anticoagulants are increasingly prescribed, representing an important alternative to the standard of care low molecular weight heparins in selected cases. The development of new anticoagulant drugs such as factors XI and XII inhibitors may offer further advantages in this context.

Conclusions

The management of CRT is still challenging with constant need for updated evidence to support tailored approaches.

背景导管相关血栓形成（CRT）是影响留置静脉导管患者的主要并发症之一，通常涉及上肢深静脉系统。这种情况可能导致肺栓塞和败血症等危及生命的并发症。发生 CRT 的风险因导管类型和患者特征而异。尽管材料和技术不断进步，但 CRT 的实际发病率仍然相当高。关于 CRT 管理的现有证据仍存在争议，临床指南是根据与导管无关的上肢或下肢深静脉血栓的数据提出建议的。目的本叙述性综述旨在描述 CRT 的流行病学，回顾关于其管理的现有证据，并强调目前尚未满足的需求。内容CRT的管理需要在血栓进展、复发事件和全身性栓塞的风险与通常情况下脆弱患者增加的出血风险之间取得谨慎的平衡。悬而未决的问题包括导管的最佳管理以及抗凝治疗的类型和持续时间。直接口服抗凝剂的处方越来越多，在选定的病例中，它是标准护理低分子量肝素的重要替代品。在这种情况下，XI 和 XII 因子抑制剂等新型抗凝药物的开发可能会带来更多优势。

{"title":"Catheter-related deep vein thrombosis: Where are we at and where are we going? Updates and ongoing unmet clinical needs","authors":"Laura Girardi, Marcello Di Nisio, Matteo Candeloro, Emanuele Valeriani, Walter Ageno","doi":"10.1111/eci.14311","DOIUrl":"10.1111/eci.14311","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Catheter-related thrombosis (CRT) is one of the major complications affecting patients with indwelling venous catheters, usually involving the upper extremity deep venous system. This condition can lead to potentially life-threatening complications such as pulmonary embolism and sepsis. The risk of developing CRT varies depending on type of catheters and patient characteristics. Despite advances in materials and technologies, the actual incidence of CRT is still considerable. Available evidence on CRT management remains controversial, and clinical guidelines base their recommendations on data from non-catheter related upper extremity or lower extremity deep venous thromboses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This narrative review aims to describe the epidemiology of CRT, to review the available evidence on its management and to highlight the current unmet needs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>No formal search strategy was applied for the revision of the literature. The main sources of information used were Medline and guidelines from international societies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Content</h3>\u0000 \u0000 <p>The management of CRT requires a careful balance between the risk of thrombus progression, recurrent events, and systemic embolization and the increased bleeding risk in often fragile patients. Open issues include the optimal management of the catheter and the type and duration of anticoagulant therapy. Direct oral anticoagulants are increasingly prescribed, representing an important alternative to the standard of care low molecular weight heparins in selected cases. The development of new anticoagulant drugs such as factors XI and XII inhibitors may offer further advantages in this context.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The management of CRT is still challenging with constant need for updated evidence to support tailored approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0