Graham Andrew Mackay, Claire Gall, Ravi Jampana, Carolyn Sleith, Gregory Y H Lip
This is an executive summary of the recent guidance produced by the Scottish Intercollegiate Guidelines Network (SIGN) dementia guideline group with regards to the investigation of suspected dementia. This is a sub-section of the broader SIGN 168 guideline released in November 2023. The guideline group included clinicians with expertise in Old Age Psychiatry, Neurology, Radiology, and Nuclear Medicine supported by colleagues from the SIGN and Healthcare Improvement Scotland teams. There was representation from carers and support organizations with experience of dementia, to ensure the recommendations were appropriate from the perspective of the people being assessed for possible dementia and their carers. As the 2018 National Institute for Health and Clinical Excellence (NICE) dementia review included a review of the evidenced investigation of dementia, the SIGN guideline development group decided to focus on a review on the up-to-date evidence regarding the role of imaging and fluid biomarkers in the diagnosis of dementia. To give context to the consideration of more advanced diagnostic biomarker investigations, the guideline and this summary include the NICE guidance on the use of standard investigations as well as more specialist investigations. The evidence review supports consideration of the use of structural imaging, nuclear medicine imaging, and established Alzheimer's cerebrospinal fluid biomarkers (amyloid and tau) in the diagnosis of dementia. Although routine use of amyloid positron emission tomography imaging was not recommended, its potential use, under specialist direction, in patients with atypical or young-onset presentations of suspected Alzheimer's dementia was included as a clinical good practice point.
这是SIGN痴呆症指南小组最近制定的关于疑似痴呆症调查指南的执行摘要。这是2023年11月发布的更广泛的SIGN 168指南的一个子部分。该指南小组包括具有老年精神病学、神经病学、放射学和核医学专业知识的临床医生,并得到了 SIGN 和苏格兰医疗保健改善(HIS)团队同事的支持。有痴呆症经验的照护者和支持组织也派代表参与其中,以确保从被评估为可能患有痴呆症的患者及其照护者的角度出发,提出适当的建议。由于2018年国家健康与临床优化研究所(NICE)痴呆症审查包括对痴呆症证据调查的审查,SIGN指南制定小组决定重点审查成像和体液生物标志物在痴呆症诊断中作用的最新证据。为了给更先进的诊断生物标志物检查提供背景信息,该指南和本摘要包括了关于使用标准检查和更专业检查的NICE指南。证据审查支持在诊断痴呆症时考虑使用结构成像、核医学成像和已确立的阿尔茨海默氏症脑脊液(CSF)生物标志物(淀粉样蛋白和 tau)。虽然不建议常规使用淀粉样蛋白 PET 成像,但其在专家指导下用于非典型或年轻发病的疑似阿尔茨海默氏症痴呆患者的可能性被列为临床良好实践点。
{"title":"Scottish Intercollegiate Guidelines Network Guidance on Dementia: The Investigation of Suspected Dementia (SIGN 168) with Focus on Biomarkers-Executive Summary.","authors":"Graham Andrew Mackay, Claire Gall, Ravi Jampana, Carolyn Sleith, Gregory Y H Lip","doi":"10.1055/a-2332-6426","DOIUrl":"10.1055/a-2332-6426","url":null,"abstract":"<p><p>This is an executive summary of the recent guidance produced by the Scottish Intercollegiate Guidelines Network (SIGN) dementia guideline group with regards to the investigation of suspected dementia. This is a sub-section of the broader SIGN 168 guideline released in November 2023. The guideline group included clinicians with expertise in Old Age Psychiatry, Neurology, Radiology, and Nuclear Medicine supported by colleagues from the SIGN and Healthcare Improvement Scotland teams. There was representation from carers and support organizations with experience of dementia, to ensure the recommendations were appropriate from the perspective of the people being assessed for possible dementia and their carers. As the 2018 National Institute for Health and Clinical Excellence (NICE) dementia review included a review of the evidenced investigation of dementia, the SIGN guideline development group decided to focus on a review on the up-to-date evidence regarding the role of imaging and fluid biomarkers in the diagnosis of dementia. To give context to the consideration of more advanced diagnostic biomarker investigations, the guideline and this summary include the NICE guidance on the use of standard investigations as well as more specialist investigations. The evidence review supports consideration of the use of structural imaging, nuclear medicine imaging, and established Alzheimer's cerebrospinal fluid biomarkers (amyloid and tau) in the diagnosis of dementia. Although routine use of amyloid positron emission tomography imaging was not recommended, its potential use, under specialist direction, in patients with atypical or young-onset presentations of suspected Alzheimer's dementia was included as a clinical good practice point.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094243","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}
Benoît Guillet, Maxime Pawlowski, Pierre Boisseau, Yohann Répessé, Philippe Beurrier, Sophie Bayart, Xavier Delavenne, Marc Trossaërt, Peter J Lenting
Background: Desmopressin (DDAVP) is used in patients with moderate/mild hemophilia A (PWMHs) to increase their factor VIII (FVIII) level and, if possible, normalize it. However, its effectiveness varies between individuals. The GIDEMHA study aims to investigate the influence of F8 gene variants.
Material and methods: The study collected the trajectory of FVIII levels from therapeutic intravenous DDAVP tests in four French hemophilia treatment centers. A pharmacological analysis was performed associated with efficacy scores according to F8 variants: absolute and relative responses, as well as new scores: absolute duration (based on duration with FVIII ≥ 0.50 IU.mL-1) and relative duration (based on half-life).
Results: From enrolled 439 PWMHs, 327 had a hot-spot F8 variant (with ≥5 PWMHs). For these, the median (min-max) basal and peak FVIII were 0.20 (0.02-0.040) and 0.74 (0.14-2.18) IU.mL-1 respectively, with FVIII recovery being 3.80 IU.ml-1 (1.15-14.75). The median FVIII half-life was 3.9 hours (0.7-15.9 hours). FVIII was normalized (≥0.50 IU.mL-1) in 224/327 PWMHs (69%) and the median time with normalized FVIII was 3.9 hours (0.0-54.1 hours). Following the response profiles to DDAVP defined by the four efficacy scores, four groups of F8 variants were isolated, and then compared using survival curves with normalized FVIII (p < 0.0001): "long-lastingly effective" [p.(Glu739Lys), p.(Ser2030Asn), p.(Arg2178His), p.(Gln2208Glu), and T-stretch deletion in intron 13]; "moderately effective" [p.(Ser112Phe), p.(Ala219Thr), p.(Thr2105Ile), p.Phe2146Ser), and p.(Asp2150Asn)]; "moderately ineffective" [p.Ala81Asp), p.(Gln324Pro), p.(Tyr492His), p.(Arg612Cys), p.(Met701Val), p.(Val2035Asn), and p.(Arg2178Cys)]; and "frequently ineffective" [c.-219C > T, p.(Cys2040Tyr), p.(Tyr2169His), p.(Pro2319Leu), and p.(Arg2326Gln)].
Conclusion: In view of our data, we propose indications for DDAVP use in PWMH based on F8 variants for minor and major invasive procedures.
{"title":"Genotype-Dependent Response to Desmopressin in Hemophilia A and Proposal of a Predictive Response Score.","authors":"Benoît Guillet, Maxime Pawlowski, Pierre Boisseau, Yohann Répessé, Philippe Beurrier, Sophie Bayart, Xavier Delavenne, Marc Trossaërt, Peter J Lenting","doi":"10.1055/a-2329-3375","DOIUrl":"10.1055/a-2329-3375","url":null,"abstract":"<p><strong>Background: </strong> Desmopressin (DDAVP) is used in patients with moderate/mild hemophilia A (PWMHs) to increase their factor VIII (FVIII) level and, if possible, normalize it. However, its effectiveness varies between individuals. The GIDEMHA study aims to investigate the influence of <i>F8</i> gene variants.</p><p><strong>Material and methods: </strong> The study collected the trajectory of FVIII levels from therapeutic intravenous DDAVP tests in four French hemophilia treatment centers. A pharmacological analysis was performed associated with efficacy scores according to <i>F8</i> variants: absolute and relative responses, as well as new scores: absolute duration (based on duration with FVIII ≥ 0.50 IU.mL<sup>-1</sup>) and relative duration (based on half-life).</p><p><strong>Results: </strong> From enrolled 439 PWMHs, 327 had a hot-spot <i>F8</i> variant (with ≥5 PWMHs). For these, the median (min-max) basal and peak FVIII were 0.20 (0.02-0.040) and 0.74 (0.14-2.18) IU.mL<sup>-1</sup> respectively, with FVIII recovery being 3.80 IU.ml<sup>-1</sup> (1.15-14.75). The median FVIII half-life was 3.9 hours (0.7-15.9 hours). FVIII was normalized (≥0.50 IU.mL<sup>-1</sup>) in 224/327 PWMHs (69%) and the median time with normalized FVIII was 3.9 hours (0.0-54.1 hours). Following the response profiles to DDAVP defined by the four efficacy scores, four groups of <i>F8</i> variants were isolated, and then compared using survival curves with normalized FVIII (<i>p</i> < 0.0001): \"long-lastingly effective\" [p.(Glu739Lys), p.(Ser2030Asn), p.(Arg2178His), p.(Gln2208Glu), and T-stretch deletion in intron 13]; \"moderately effective\" [p.(Ser112Phe), p.(Ala219Thr), p.(Thr2105Ile), p.Phe2146Ser), and p.(Asp2150Asn)]; \"moderately ineffective\" [p.Ala81Asp), p.(Gln324Pro), p.(Tyr492His), p.(Arg612Cys), p.(Met701Val), p.(Val2035Asn), and p.(Arg2178Cys)]; and \"frequently ineffective\" [c.-219C > T, p.(Cys2040Tyr), p.(Tyr2169His), p.(Pro2319Leu), and p.(Arg2326Gln)].</p><p><strong>Conclusion: </strong> In view of our data, we propose indications for DDAVP use in PWMH based on <i>F8</i> variants for minor and major invasive procedures.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959589","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":"Commentary: \"No Genetic Causality between Tobacco Smoking and Venous Thromboembolism: A Two-Sample Mendelian Randomization Study\".","authors":"Jinhua Liu, Youqian Zhang, Bo Zeng","doi":"10.1055/s-0044-1787653","DOIUrl":"https://doi.org/10.1055/s-0044-1787653","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284849","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}
Pub Date : 2024-06-01Epub Date: 2023-12-11DOI: 10.1055/a-2225-5513
Francisco Ujueta
{"title":"Low Dietary Manganese and the Incidence of Venous Thromboembolism: Evidence for Minerals and Vitamins and the Other Comorbidities Linked to Venous Thromboembolism.","authors":"Francisco Ujueta","doi":"10.1055/a-2225-5513","DOIUrl":"10.1055/a-2225-5513","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138800524","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}
Pub Date : 2024-06-01Epub Date: 2023-12-11DOI: 10.1055/a-2225-5173
Timm Zahn, Nancy Schanze, Dawid L Staudacher, Tobias Wengenmayer, Sven Maier, Christoph Benk, Nadine Gauchel, Daniel Duerschmied, Alexander Supady
Background: Post-cardiac arrest syndrome (PCAS) is a frequent complication following successful cardiopulmonary resuscitation and correlates with poor outcome. PCAS is characterized by an excessive inflammatory response to whole-body ischemia and reperfusion. Cytokine adsorption was suggested as an adjunctive treatment option for the removal of cytokines from the patients' blood to restore the physiological equilibrium of pro- and anti-inflammatory activity and thus mitigate hemodynamic instability and end-organ complications.
Material and methods: To better understand the cellular effects of cytokine adsorption in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR) after in- and out-of-hospital cardiac arrest, we compared the activation status of neutrophils, monocytes, and platelets as well as the formation of platelet-leukocyte complexes in intravenous whole blood samples from an exploratory subgroup (n = 24) from the randomized CYTER study.
Result: At 48 hours after initiation of ECPR, flow cytometry analyses did neither reveal significant differences in neutrophil (CD11b, CD66b, L-selectin, and PSGL-1) and monocyte (CD11b, L-selectin, and PSGL-1) surface molecule expression nor in circulating platelet-monocyte complexes between patients receiving cytokine adsorption and those without.
Conclusion: Data did not show a relevant effect of cytokine adsorption on neutrophil and monocyte activation during the first 48 hours after initiation of ECPR.
{"title":"The Effect of Cytokine Adsorption on Leukocyte and Platelet Activation after Extracorporeal Cardiopulmonary Resuscitation.","authors":"Timm Zahn, Nancy Schanze, Dawid L Staudacher, Tobias Wengenmayer, Sven Maier, Christoph Benk, Nadine Gauchel, Daniel Duerschmied, Alexander Supady","doi":"10.1055/a-2225-5173","DOIUrl":"10.1055/a-2225-5173","url":null,"abstract":"<p><strong>Background: </strong> Post-cardiac arrest syndrome (PCAS) is a frequent complication following successful cardiopulmonary resuscitation and correlates with poor outcome. PCAS is characterized by an excessive inflammatory response to whole-body ischemia and reperfusion. Cytokine adsorption was suggested as an adjunctive treatment option for the removal of cytokines from the patients' blood to restore the physiological equilibrium of pro- and anti-inflammatory activity and thus mitigate hemodynamic instability and end-organ complications.</p><p><strong>Material and methods: </strong> To better understand the cellular effects of cytokine adsorption in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR) after in- and out-of-hospital cardiac arrest, we compared the activation status of neutrophils, monocytes, and platelets as well as the formation of platelet-leukocyte complexes in intravenous whole blood samples from an exploratory subgroup (<i>n</i> = 24) from the randomized CYTER study.</p><p><strong>Result: </strong> At 48 hours after initiation of ECPR, flow cytometry analyses did neither reveal significant differences in neutrophil (CD11b, CD66b, L-selectin, and PSGL-1) and monocyte (CD11b, L-selectin, and PSGL-1) surface molecule expression nor in circulating platelet-monocyte complexes between patients receiving cytokine adsorption and those without.</p><p><strong>Conclusion: </strong> Data did not show a relevant effect of cytokine adsorption on neutrophil and monocyte activation during the first 48 hours after initiation of ECPR.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801136","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}
Pub Date : 2024-06-01Epub Date: 2023-11-20DOI: 10.1055/a-2213-9230
Cindy M M de Jong, Wilbert B van den Hout, Christel E van Dijk, Noor Heim, Lisette F van Dam, Charlotte E A Dronkers, Gargi Gautam, Waleed Ghanima, Jostein Gleditsch, Anders von Heijne, Herman M A Hofstee, Marcel M C Hovens, Menno V Huisman, Stan Kolman, Albert T A Mairuhu, Thijs E van Mens, Mathilde Nijkeuter, Marcel A van de Ree, Cornelis J van Rooden, Robin E Westerbeek, Jan Westerink, Eli Westerlund, Lucia J M Kroft, Frederikus A Klok
Background: The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) with compression ultrasonography (CUS) may be hindered by residual intravascular obstruction after previous DVT. A reference CUS, an additional ultrasound performed at anticoagulant discontinuation, may improve the diagnostic work-up of suspected recurrent ipsilateral DVT by providing baseline images for future comparison.
Objectives: To evaluate the cost-effectiveness of routinely performing reference CUS in DVT patients.
Methods: Patient-level data (n = 96) from a prospective management study (Theia study; NCT02262052) and claims data were used in a decision analytic model to compare 12 scenarios for diagnostic management of suspected recurrent ipsilateral DVT. Estimated health care costs and mortality due to misdiagnosis, recurrent venous thromboembolism, and bleeding during the first year of follow-up after presentation with suspected recurrence were compared.
Results: All six scenarios including reference CUS had higher estimated 1-year costs (€1,763-€1,913) than the six without reference CUS (€1,192-€1,474). Costs were higher because reference CUS results often remained unused, as 20% of patients (according to claims data) would return with suspected recurrent DVT. Estimated mortality was comparable in scenarios with (14.8-17.9 per 10,000 patients) and without reference CUS (14.0-18.5 per 10,000). None of the four potentially most desirable scenarios included reference CUS.
Conclusion: One-year health care costs of diagnostic strategies for suspected recurrent ipsilateral DVT including reference CUS are higher compared to strategies without reference CUS, without mortality benefit. These results can inform policy-makers regarding use of health care resources during follow-up after DVT. From a cost-effectiveness perspective, the findings do not support the routine application of reference CUS.
{"title":"Cost-Effectiveness of Performing Reference Ultrasonography in Patients with Deep Vein Thrombosis.","authors":"Cindy M M de Jong, Wilbert B van den Hout, Christel E van Dijk, Noor Heim, Lisette F van Dam, Charlotte E A Dronkers, Gargi Gautam, Waleed Ghanima, Jostein Gleditsch, Anders von Heijne, Herman M A Hofstee, Marcel M C Hovens, Menno V Huisman, Stan Kolman, Albert T A Mairuhu, Thijs E van Mens, Mathilde Nijkeuter, Marcel A van de Ree, Cornelis J van Rooden, Robin E Westerbeek, Jan Westerink, Eli Westerlund, Lucia J M Kroft, Frederikus A Klok","doi":"10.1055/a-2213-9230","DOIUrl":"10.1055/a-2213-9230","url":null,"abstract":"<p><strong>Background: </strong> The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) with compression ultrasonography (CUS) may be hindered by residual intravascular obstruction after previous DVT. A reference CUS, an additional ultrasound performed at anticoagulant discontinuation, may improve the diagnostic work-up of suspected recurrent ipsilateral DVT by providing baseline images for future comparison.</p><p><strong>Objectives: </strong> To evaluate the cost-effectiveness of routinely performing reference CUS in DVT patients.</p><p><strong>Methods: </strong> Patient-level data (<i>n</i> = 96) from a prospective management study (Theia study; NCT02262052) and claims data were used in a decision analytic model to compare 12 scenarios for diagnostic management of suspected recurrent ipsilateral DVT. Estimated health care costs and mortality due to misdiagnosis, recurrent venous thromboembolism, and bleeding during the first year of follow-up after presentation with suspected recurrence were compared.</p><p><strong>Results: </strong> All six scenarios including reference CUS had higher estimated 1-year costs (€1,763-€1,913) than the six without reference CUS (€1,192-€1,474). Costs were higher because reference CUS results often remained unused, as 20% of patients (according to claims data) would return with suspected recurrent DVT. Estimated mortality was comparable in scenarios with (14.8-17.9 per 10,000 patients) and without reference CUS (14.0-18.5 per 10,000). None of the four potentially most desirable scenarios included reference CUS.</p><p><strong>Conclusion: </strong> One-year health care costs of diagnostic strategies for suspected recurrent ipsilateral DVT including reference CUS are higher compared to strategies without reference CUS, without mortality benefit. These results can inform policy-makers regarding use of health care resources during follow-up after DVT. From a cost-effectiveness perspective, the findings do not support the routine application of reference CUS.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138177347","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}
Pub Date : 2024-06-01Epub Date: 2023-11-20DOI: 10.1055/a-2213-8939
Yu Huang, Yanjun Zhang, Sisi Yang, Hao Xiang, Chun Zhou, Ziliang Ye, Mengyi Liu, Panpan He, Yuanyuan Zhang, Xiaoqin Gan, Xianhui Qin
Background: The association between dietary manganese (Mn) intake and the risk of venous thromboembolism (VTE) remains unknown. We aimed to investigate the associations of dietary Mn intake with incident VTE, and the underlying mediating roles of obesity markers (body mass index [BMI] and waist circumference), hemorheological parameters (red cell distribution width [RDW], platelet count [PLT], and mean platelet volume [MPV]), and inflammatory biomarkers (C-reactive protein [CRP] and white blood cell count [WBC]) in this association.
Methods: A total of 202,507 adults from the UK Biobank with complete dietary data and without VTE at baseline were included. Dietary information was collected by the online 24-hour diet recall questionnaires (Oxford WebQ). The primary outcome was incident VTE, a composite of incident deep vein thrombosis (DVT) and pulmonary embolism (PE).
Results: During a median follow-up of 11.6 years, 4,750 participants developed incident VTE. Overall, there were significantly inverse relationships of dietary Mn intake with incident VTE (per 1 mg/day increment; adjusted hazard ratio [HR]: 0.92; 95% confidence interval [CI]: 0.90-0.95), incident DVT (per 1 mg/day increment; adjusted HR: 0.93; 95% CI: 0. 90-0.96), and incident PE (per 1 mg/day increment; adjusted HR: 0.91; 95% CI: 0.88-0.95). BMI, waist circumference, RDW, CRP, and WBC significantly mediated the association between dietary Mn intake and incident VTE, with the mediated proportions of 36.0, 36.5, 4.2, 4.3, and 1.6%, respectively. However, MPV and PLT did not significantly mediate the association.
Conclusion: Our study shows that dietary Mn intake was inversely associated with incident VTE. The inverse association was mainly mediated by obesity, followed by inflammatory biomarkers and RDW. Our findings are just hypothesis-generating, and further confirmation of our findings in more studies is essential.
{"title":"Association and Pathways between Dietary Manganese Intake and Incident Venous Thromboembolism.","authors":"Yu Huang, Yanjun Zhang, Sisi Yang, Hao Xiang, Chun Zhou, Ziliang Ye, Mengyi Liu, Panpan He, Yuanyuan Zhang, Xiaoqin Gan, Xianhui Qin","doi":"10.1055/a-2213-8939","DOIUrl":"10.1055/a-2213-8939","url":null,"abstract":"<p><strong>Background: </strong> The association between dietary manganese (Mn) intake and the risk of venous thromboembolism (VTE) remains unknown. We aimed to investigate the associations of dietary Mn intake with incident VTE, and the underlying mediating roles of obesity markers (body mass index [BMI] and waist circumference), hemorheological parameters (red cell distribution width [RDW], platelet count [PLT], and mean platelet volume [MPV]), and inflammatory biomarkers (C-reactive protein [CRP] and white blood cell count [WBC]) in this association.</p><p><strong>Methods: </strong> A total of 202,507 adults from the UK Biobank with complete dietary data and without VTE at baseline were included. Dietary information was collected by the online 24-hour diet recall questionnaires (Oxford WebQ). The primary outcome was incident VTE, a composite of incident deep vein thrombosis (DVT) and pulmonary embolism (PE).</p><p><strong>Results: </strong> During a median follow-up of 11.6 years, 4,750 participants developed incident VTE. Overall, there were significantly inverse relationships of dietary Mn intake with incident VTE (per 1 mg/day increment; adjusted hazard ratio [HR]: 0.92; 95% confidence interval [CI]: 0.90-0.95), incident DVT (per 1 mg/day increment; adjusted HR: 0.93; 95% CI: 0. 90-0.96), and incident PE (per 1 mg/day increment; adjusted HR: 0.91; 95% CI: 0.88-0.95). BMI, waist circumference, RDW, CRP, and WBC significantly mediated the association between dietary Mn intake and incident VTE, with the mediated proportions of 36.0, 36.5, 4.2, 4.3, and 1.6%, respectively. However, MPV and PLT did not significantly mediate the association.</p><p><strong>Conclusion: </strong> Our study shows that dietary Mn intake was inversely associated with incident VTE. The inverse association was mainly mediated by obesity, followed by inflammatory biomarkers and RDW. Our findings are just hypothesis-generating, and further confirmation of our findings in more studies is essential.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138177346","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}
Pub Date : 2024-06-01Epub Date: 2023-08-18DOI: 10.1055/a-2156-7872
Yasushi Ueki, Jonas D Häner, Sylvain Losdat, Giuseppe Gargiulo, Hiroki Shibutani, Sarah Bär, Tatsuhiko Otsuka, Raminta Kavaliauskaite, Vera R Mitter, Fabrice Temperli, David Spirk, Stefan Stortecky, George C M Siontis, Marco Valgimigli, Stephan Windecker, Clemens Gutmann, Konstantinos C Koskinas, Manuel Mayr, Lorenz Räber
Objective: The effect of the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown. We aimed to explore the effect of alirocumab added to high-intensity statin therapy on P2Y12 reaction unit (PRU) among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel). In addition, we assessed circulating platelet-derived noncoding RNAs (microRNAs and YRNAs).
Methods: This was a prespecified, powered, pharmacodynamic substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Patients recruited at Bern University Hospital, receiving DAPT with a potent P2Y12 inhibitor, and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The primary endpoint was PRU at 4 weeks after study drug initiation as assessed by VerifyNow P2Y12 point-of-care assays.
Results: Among 139 randomized patients, the majority of patients received ticagrelor DAPT at 4 weeks (57 [86.4%] in the alirocumab group vs. 69 [94.5%] in the placebo group, p = 0.14). There were no significant differences in the primary endpoint PRU at 4 weeks between groups (12.5 [interquartile range, IQR: 27.0] vs. 19.0 [IQR: 30.0], p = 0.26). Consistent results were observed in 126 patients treated with ticagrelor (13.0 [IQR: 20.0] vs. 18.0 [IQR: 27.0], p = 0.28). Similarly, platelet-derived noncoding RNAs did not significantly differ between groups.
Conclusion: Among AMI patients receiving DAPT with a potent P2Y12 inhibitor, alirocumab had no significant effect on platelet reactivity as assessed by PRU and platelet-derived noncoding RNAs.
{"title":"Effect of Alirocumab Added to High-Intensity Statin on Platelet Reactivity and Noncoding RNAs in Patients with AMI: A Substudy of the PACMAN-AMI Trial.","authors":"Yasushi Ueki, Jonas D Häner, Sylvain Losdat, Giuseppe Gargiulo, Hiroki Shibutani, Sarah Bär, Tatsuhiko Otsuka, Raminta Kavaliauskaite, Vera R Mitter, Fabrice Temperli, David Spirk, Stefan Stortecky, George C M Siontis, Marco Valgimigli, Stephan Windecker, Clemens Gutmann, Konstantinos C Koskinas, Manuel Mayr, Lorenz Räber","doi":"10.1055/a-2156-7872","DOIUrl":"10.1055/a-2156-7872","url":null,"abstract":"<p><strong>Objective: </strong> The effect of the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown. We aimed to explore the effect of alirocumab added to high-intensity statin therapy on P2Y12 reaction unit (PRU) among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel). In addition, we assessed circulating platelet-derived noncoding RNAs (microRNAs and YRNAs).</p><p><strong>Methods: </strong> This was a prespecified, powered, pharmacodynamic substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Patients recruited at Bern University Hospital, receiving DAPT with a potent P2Y12 inhibitor, and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The primary endpoint was PRU at 4 weeks after study drug initiation as assessed by VerifyNow P2Y12 point-of-care assays.</p><p><strong>Results: </strong> Among 139 randomized patients, the majority of patients received ticagrelor DAPT at 4 weeks (57 [86.4%] in the alirocumab group vs. 69 [94.5%] in the placebo group, <i>p</i> = 0.14). There were no significant differences in the primary endpoint PRU at 4 weeks between groups (12.5 [interquartile range, IQR: 27.0] vs. 19.0 [IQR: 30.0], <i>p</i> = 0.26). Consistent results were observed in 126 patients treated with ticagrelor (13.0 [IQR: 20.0] vs. 18.0 [IQR: 27.0], <i>p</i> = 0.28). Similarly, platelet-derived noncoding RNAs did not significantly differ between groups.</p><p><strong>Conclusion: </strong> Among AMI patients receiving DAPT with a potent P2Y12 inhibitor, alirocumab had no significant effect on platelet reactivity as assessed by PRU and platelet-derived noncoding RNAs.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10209013","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}
Pub Date : 2024-06-01Epub Date: 2024-03-19DOI: 10.1055/s-0044-1782161
Luis Ortega-Paz, Francesco Franchi, Dominick J Angiolillo
{"title":"The Lipid-Platelet Interplay: Unraveling the Effects of PCSK9 Inhibition on Platelet Reactivity.","authors":"Luis Ortega-Paz, Francesco Franchi, Dominick J Angiolillo","doi":"10.1055/s-0044-1782161","DOIUrl":"10.1055/s-0044-1782161","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176597","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}
Background: Intra-plaque hemorrhage (IPH) leads to rapid plaque progression and instability through upregulation of matrix metalloproteinases (MMPs) and collagen degradation. Hemoglobin-derived hemin during IPH promotes plaque instability. We investigated whether hemin affects MMP overexpression in macrophages and explored the underlying mechanisms.
Material and methods: In vivo, hemorrhagic plaque models were established in rabbits and ApoE-/- mice. Ferrostatin-1 was used to inhibit ferroptosis. Plaque size, collagen, and MMP2/9 levels were evaluated using immunohistochemistry, H&E, Sirius Red, and Masson staining. In vitro, mouse peritoneal macrophages were extracted. Western blot and ELISA were used to measure MMP2/9 levels. Bioinformatics analysis investigated the association between MMPs and ferroptosis pathway genes. Macrophage ferroptosis was assessed by evaluating cell viability, lipid reactive oxygen species, mitochondrial ultrastructure, iron content, and COX2 levels after pretreatment with cell death inhibitors. Hemin's impact on ferroptosis and MMP expression was studied using Ferrostatin-1 and SB202190.
Results: In the rabbit hemorrhagic plaques, hemin deposition and overexpression of MMP2/9 were observed, particularly in macrophage-enriched regions. In vitro, hemin induced ferroptosis and MMP2/9 expression in macrophages. Ferrostatin-1 and SB202190 inhibited hemin-induced MMP2/9 overexpression. Ferrostatin-1 inhibited p38 phosphorylation in macrophages. Ferostatin-1 inhibits macrophage ferroptosis, reduces MMP2/9 levels in plaques, and stabilizes the hemorrhagic plaques.
Conclusion: Our results suggested that hemin-induced macrophage ferroptosis promotes p38 pathway activation and MMP2/9 overexpression, which may play a crucial role in increasing hemorrhagic plaque vulnerability. These findings provide insights into the pathogenesis of hemorrhagic plaques and suggest that targeting macrophage ferroptosis may be a promising strategy for stabilizing vulnerable plaque.
{"title":"Macrophage Ferroptosis Promotes MMP2/9 Overexpression Induced by Hemin in Hemorrhagic Plaque.","authors":"Bicheng Li, Minqiao Lu, Hui Wang, Siqi Sheng, Shuyuan Guo, Jia Li, Ye Tian","doi":"10.1055/a-2173-3602","DOIUrl":"10.1055/a-2173-3602","url":null,"abstract":"<p><strong>Background: </strong> Intra-plaque hemorrhage (IPH) leads to rapid plaque progression and instability through upregulation of matrix metalloproteinases (MMPs) and collagen degradation. Hemoglobin-derived hemin during IPH promotes plaque instability. We investigated whether hemin affects MMP overexpression in macrophages and explored the underlying mechanisms.</p><p><strong>Material and methods: </strong> In vivo, hemorrhagic plaque models were established in rabbits and ApoE<sup>-/-</sup> mice. Ferrostatin-1 was used to inhibit ferroptosis. Plaque size, collagen, and MMP2/9 levels were evaluated using immunohistochemistry, H&E, Sirius Red, and Masson staining. In vitro, mouse peritoneal macrophages were extracted. Western blot and ELISA were used to measure MMP2/9 levels. Bioinformatics analysis investigated the association between MMPs and ferroptosis pathway genes. Macrophage ferroptosis was assessed by evaluating cell viability, lipid reactive oxygen species, mitochondrial ultrastructure, iron content, and COX2 levels after pretreatment with cell death inhibitors. Hemin's impact on ferroptosis and MMP expression was studied using Ferrostatin-1 and SB202190.</p><p><strong>Results: </strong> In the rabbit hemorrhagic plaques, hemin deposition and overexpression of MMP2/9 were observed, particularly in macrophage-enriched regions. In vitro, hemin induced ferroptosis and MMP2/9 expression in macrophages. Ferrostatin-1 and SB202190 inhibited hemin-induced MMP2/9 overexpression. Ferrostatin-1 inhibited p38 phosphorylation in macrophages. Ferostatin-1 inhibits macrophage ferroptosis, reduces MMP2/9 levels in plaques, and stabilizes the hemorrhagic plaques.</p><p><strong>Conclusion: </strong> Our results suggested that hemin-induced macrophage ferroptosis promotes p38 pathway activation and MMP2/9 overexpression, which may play a crucial role in increasing hemorrhagic plaque vulnerability. These findings provide insights into the pathogenesis of hemorrhagic plaques and suggest that targeting macrophage ferroptosis may be a promising strategy for stabilizing vulnerable plaque.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10203614","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}