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Statin-associated regulation of hepatic PNPLA3 in patients without known liver disease. 他汀类药物对无已知肝病患者肝脏 PNPLA3 的相关调节。
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-19 DOI: 10.1111/joim.20032
Osman Ahmed, Vladimir S Shavva, Laura Tarnawski, Wanmin Dai, Filip Borg, Viggo V Olofsson, Ting Liu, Peter Saliba-Gustafsson, Christian Simini, Matteo Pedrelli, Otto Bergman, Giuseppe Danilo Norata, Paolo Parini, Anders Franco-Cereceda, Per Eriksson, Stephen G Malin, Hanna M Björck, Peder S Olofsson

Background and objectives: Statins are used for metabolic dysfunction-associated steatotic liver disease (MASLD) (NAFLD) treatment, but their role in this context is unclear. Genetic variants of patatin-like phospholipase domain containing 3 (PNPLA3) are associated with MASLD susceptibility and statin treatment efficacy. Access to liver biopsies before established MASLD is limited, and statins and PNPLA3 in early liver steatosis are thus difficult to study.

Methods: Liver biopsies were collected from 261 patients without known liver disease at surgery and stratified based on statin use and criteria for the metabolic syndrome (MS). Genotypes and transcript levels were measured using Illumina and Affymetrix arrays, and metabolic and lipoprotein profiles by clinical assays. Statin effects on PNPLA3, de novo lipogenesis (DNL), and lipid accumulation were further studied in vitro.

Results: The PNPLA3I148M genetic variant was associated with significantly lower hepatic levels of cholesterol synthesis-associated transcripts. Patients with MS had significantly higher hepatic levels of MASLD and lipogenesis-associated transcripts than non-MS patients. Patients with MS on statin therapy had significantly higher hepatic levels of PNPLA3, acetyl-CoA carboxylase alpha, and ATP citrate lyase, and statin use was associated with higher plasma fasting glucose, insulin, and HbA1c. Exposure of hepatocyte-like HepG2 cells to atorvastatin promoted intracellular accumulation of triglycerides and lipogenesis-associated transcripts. Atorvastatin-exposure of HepG2, sterol O-acyltransferase (SOAT) 2-only-HepG2, primary human hepatic stellate, and hepatic stellate cell-like LX2 cells significantly increased levels of PNPLA3 and SREBF2-target genes, whereas knockdown of SREBF2 attenuated this effect.

Conclusions: Collectively, these observations suggest statin-associated regulation of PNPLA3 and DNL in liver. The potential interaction between PNPLA3 genotype and metabolic status should be considered in future studies in the context of statin therapy for MASLD.

背景和目的:他汀类药物用于代谢功能障碍相关性脂肪性肝病(MASLD)(NAFLD)的治疗,但其在这方面的作用尚不清楚。含帕他丁样磷脂酶域 3 (PNPLA3) 的基因变异与 MASLD 易感性和他汀类药物的疗效有关。在确诊 MASLD 之前进行肝活检的机会有限,因此很难对他汀类药物和 PNPLA3 在早期肝脏脂肪变性中的作用进行研究:方法:收集了261名手术时未发现肝病的患者的肝活检组织,并根据他汀类药物的使用情况和代谢综合征(MS)的标准进行了分层。使用 Illumina 和 Affymetrix 阵列测量基因型和转录本水平,并使用临床检测方法测量代谢和脂蛋白概况。在体外进一步研究了他汀类药物对 PNPLA3、新生脂肪生成(DNL)和脂质累积的影响:结果:PNPLA3I148M 基因变异与肝脏胆固醇合成相关转录物水平显著降低有关。与非多发性硬化症患者相比,多发性硬化症患者肝脏中的 MASLD 和脂肪生成相关转录本水平明显较高。接受他汀类药物治疗的多发性硬化症患者的肝脏中 PNPLA3、乙酰-CoA 羧化酶 alpha 和 ATP 柠檬酸酶的水平明显较高,他汀类药物的使用与较高的血浆空腹血糖、胰岛素和 HbA1c 有关。将肝细胞样 HepG2 细胞暴露于阿托伐他汀可促进细胞内甘油三酯和脂肪生成相关转录物的积累。将阿托伐他汀暴露于HepG2、固醇O-酰基转移酶(SOAT)2-only-HepG2、原代人类肝星状细胞和肝星状细胞样LX2细胞可显著增加PNPLA3和SREBF2靶基因的水平,而敲除SREBF2可减轻这种影响:总之,这些观察结果表明他汀类药物对肝脏中的 PNPLA3 和 DNL 有相关调控作用。在他汀类药物治疗MASLD的背景下,未来的研究应考虑PNPLA3基因型与代谢状态之间的潜在相互作用。
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引用次数: 0
Different ways of diagnosing selective glomerular hypofiltration syndromes such as shrunken pore syndrome and the associated increase in mortality. 选择性肾小球低滤过综合征(如缩孔综合征)的不同诊断方法及相关死亡率的增加。
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-19 DOI: 10.1111/joim.20035
Anna Åkesson, Linnea Malmgren, Felicia Leion, Ulf Nyman, Anders Christensson, Jonas Björk, Anders Grubb

Background: In 2015, a selective decrease in the glomerular filtration of middle-sized molecules such as cystatin C compared to small molecules such as creatinine was first described and tentatively termed "Shrunken pore syndrome." Numerous studies have thereafter found an association between this syndrome (defined by a low eGFRcystatin C to eGFRcreatinine ratio) and mortality and morbidity. In 2023, the syndrome was renamed selective glomerular hypofiltration syndromes (SGHS) as shrunken pores are not the only pathophysiological mechanism. Recently, some studies have used the difference between eGFRcystatin C and eGFRcreatinine to describe a similar disorder, and this investigation compares the two measures.

Methods: Using a cohort of 2781 adults with a median follow-up of 5.6 years, referred for determination of glomerular filtration rate (GFR), estimated GFR (eGFR) was determined using four equations. SGHS was defined using the eGFRdifference and the eGFRratio and association to mortality investigated through adjusted Cox proportional hazard models. From each adjusted regression model, Harrell's C-index and 95% confidence intervals were calculated.

Results: Both measures were associated with mortality. No significant differences concerning hazard ratios or Harrell's C-index were found between the two measures to estimate mortality, and both identified SGHS and increased mortality in a subpopulation of 567 "healthy" individuals with no prior diagnosis and with no kidney disorder according to the kidney disease improving global outcomes-criteria.

Conclusion: The eGFRdifference is not superior to the eGFRratio in diagnosing SGHS or estimating mortality. However, as the two measures do not identify the same subpopulation, using them simultaneously might improve risk stratification.

背景:2015 年,人们首次描述了胱抑素 C 等中等大小分子与肌酐等小分子相比肾小球滤过率选择性下降的现象,并将其暂称为 "缩孔综合征"。此后,大量研究发现,该综合征(定义为低 eGFR 胱抑素 C 与 eGFR 肌酐比值)与死亡率和发病率之间存在关联。2023 年,该综合征被重新命名为选择性肾小球低滤过综合征(SGHS),因为毛孔缩小并不是唯一的病理生理机制。最近,一些研究利用 eGFRcystatin C 和 eGFRcreatinine 之间的差异来描述一种类似的疾病,本研究对这两种测量方法进行了比较:通过对中位随访时间为 5.6 年的 2781 名成年人进行队列研究,采用四种方程确定了肾小球滤过率(GFR)的估算值(eGFR)。使用 eGFRdifference 和 eGFRratio 对 SGHS 进行定义,并通过调整后的 Cox 比例危险模型研究其与死亡率的关系。根据每个调整后的回归模型,计算出 Harrell 的 C 指数和 95% 的置信区间:结果:这两项指标都与死亡率有关。根据肾脏病改善全球结果标准,在 567 名既往未确诊又无肾脏疾病的 "健康 "人群中,这两种估算死亡率的方法在危险比或 Harrell's C 指数方面均未发现明显差异:在诊断 SGHS 或估算死亡率方面,eGFRdifference 并不优于 eGFRratio。然而,由于这两种测量方法不能识别相同的亚人群,同时使用可能会改善风险分层。
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引用次数: 0
Therapeutic BCG vaccine protects against long COVID: The BATTLE randomized clinical trial. 治疗性卡介苗可预防长效 COVID:BATTLE 随机临床试验。
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-19 DOI: 10.1111/joim.20033
Mehrsa Jalalizadeh, Keini Buosi, Cristiane F Giacomelli, Patricia A F Leme, Karen L Ferrari, Franciele A V Dionato, Wandrey R S Brito, Natália S Brunetti, Aline R Maia, Joseane Morari, Ana C Pagliarone, Alessandro S Farias, Licio A Velloso, Maria A F Queiroz, Antonio C R Vallinoto, Marcio C Bajgelman, Leonardo O Reis

Background: Bacillus Calmette-Guérin (BCG) injected during the COVID-19 convalescence period was safe and enhanced recovery from anosmia and dysgeusia in the acute phase.

Objectives: To report the long-term results of the BATTLE trial, BCG vaccine in adults with mild COVID-19.

Methods: Design: Double-blind, placebo-controlled, randomized (1:1) clinical trial.

Intervention: BCG intradermal vaccine and placebo.

Patients: A total of 157 BCG and 142 placebo recipients participated in the 6-month follow-up, and 97 BCG and 95 placebo recipients participated in the 12-month follow-up.

Measurements: Long COVID symptoms and mechanistic analyses.

Results: BCG reduced hearing problems at 6 months (odds ratio [OR] = 0.26) and sleeping, concentration, memory, and vision problems at 12 months (OR = 0.45, 0.36, 0.38, and 0.36, respectively). Sensitivity analyses confirmed that long COVID-19 symptoms were reduced at the 6- and 12-month follow-ups (p = 0.010 and 0.031, respectively). BCG's crossover interaction paradoxically increased hair loss in women and decreased it in men at 6 months (p = 0.032). BCG immunomodulation is likely mediated through inhibition of Fas ligand expression in the blood and increased induction of IL6, IL10, interferon-induced transmembrane protein 3, and angiotensin-converting enzyme 2 in cultured human macrophages.

Conclusion: Long-term follow-up of the BATTLE trial participants revealed that BCG protects against long COVID development if administered within the COVID-19 convalescence period. The response to BCG was subject-specific, including a paradoxical crossover interaction based on sex.

Limitations: Not tested for previous mycobacterial exposure; loss to follow-up, particularly at 12 months.

背景:在COVID-19康复期注射卡介苗(Bacillus Calmette-Guérin,BCG)是安全的,并能促进急性期嗅觉障碍和发音障碍的恢复:报告BATTLE试验(卡介苗用于轻度COVID-19成人患者)的长期结果:方法:设计:双盲、安慰剂对照、随机(1:1)临床试验:卡介苗皮内接种和安慰剂:共有157名卡介苗接种者和142名安慰剂接种者参加了6个月的随访,97名卡介苗接种者和95名安慰剂接种者参加了12个月的随访:测量:长期COVID症状和机理分析:结果:卡介苗减少了6个月时的听力问题(几率比[OR] = 0.26)和12个月时的睡眠、注意力、记忆力和视力问题(OR = 0.45、0.36、0.38和0.36)。敏感性分析证实,在 6 个月和 12 个月的随访中,COVID-19 长症状有所减轻(p = 0.010 和 0.031)。卡介苗的交叉作用矛盾地增加了女性的脱发,而在 6 个月时减少了男性的脱发(p = 0.032)。卡介苗的免疫调节作用可能是通过抑制血液中 Fas 配体的表达和增加培养的人巨噬细胞中 IL6、IL10、干扰素诱导跨膜蛋白 3 和血管紧张素转换酶 2 的诱导来实现的:对 BATTLE 试验参与者的长期随访表明,如果在 COVID-19 康复期内接种卡介苗,卡介苗可防止 COVID 长期发展。对卡介苗的反应是受试者特异性的,包括基于性别的矛盾交叉相互作用:局限性:未检测既往是否接触过分枝杆菌;随访损失,尤其是12个月的随访损失。
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引用次数: 0
Primary glomerular diseases and long-term adverse health outcomes: A nationwide cohort study. 原发性肾小球疾病与长期不良健康后果:全国性队列研究。
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-13 DOI: 10.1111/joim.20024
Anne-Laure Faucon, Stefania Lando, Charikleia Chrysostomou, Julia Wijkström, Sigrid Lundberg, Rino Bellocco, Mårten Segelmark, Marie Evans, Juan-Jesús Carrero

Background: Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide, little is known about their long-term outcomes.

Methods: In patients with chronic kidney disease (CKD) stage 3-5 enrolled in the Swedish Renal Registry, we compared risks of hospitalization, kidney replacement therapy (KRT), major cardiovascular events (MACE), and death of the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD], and membranous nephropathy [MN]), and patients with CKD due to the most common non-communicable diseases (control-CKD).

Results: We identified 2396 patients with glomerular disease (97% biopsy-proven, 69% men, 57 years, eGFR 29 mL/min/1.73 m2, uACR 88 mg/mmol, 1524 with IgAN, 398 FSGS, 94 MCD, and 380 MN) and 37,697 controls (64% men, 74 years, eGFR 25 mL/min/1.73 m2, uACR 23 mg/mmol), mainly with diabetic nephropathy and nephroangiosclerosis. The median follow-up was 6.3 (3.3; 9.9) years. Compared with control-CKD, patients with primary glomerular diseases generally had a lower risk of hospitalization, MACE (adjusted hazard ratios [HRs] ranging from 0.44 to 0.88 depending on the etiology) and death (HRs ranging 0.45-0.76). Patients with IgAN and FSGS had a faster eGFR decline and a higher rate of KRT (HRs 1.26 [95%CI: 1.15-1.37] and 1.34 [1.15-1.57], respectively). Conversely, patients with MN and MCD had a lower KRT rate and slower eGFR decline.

Conclusion: Despite having a lower relative risk of hospitalization, cardiovascular events and mortality, patients with IgAN and FSGS are at higher risk of CKD progression than the most common etiologies of CKD, emphasizing the need for more stringent treatment strategies in these patients.

背景:尽管肾小球疾病是全球第三大终末期肾病病因,但人们对其长期预后却知之甚少:尽管肾小球疾病是导致全球终末期肾病的第三大常见病因,但人们对其长期预后却知之甚少:方法:在瑞典肾脏登记处登记的慢性肾脏病(CKD)3-5 期患者中,我们比较了住院、肾脏替代治疗(KRT)、主要心血管事件(MACE)和死亡的风险、IgA肾病[IgAN]、局灶节段性肾小球硬化症[FSGS]、微小病变[MCD]和膜性肾病[MN])和最常见的非传染性疾病(对照组-CKD)导致的 CKD 患者的住院、肾脏替代治疗(KRT)、主要心血管事件(MACE)和死亡风险进行了比较。结果:我们发现了 2396 名肾小球疾病患者(97% 经活检证实,69% 男性,57 岁,eGFR 29 mL/min/1.73 m2,uACR 88 mg/mmol,1524 名 IgAN 患者,398 名 FSGS 患者,94 名 MCD 患者,380 名 MN 患者)和 37,697 名对照组患者(64% 男性,74 岁,eGFR 25 mL/min/1.73 m2,uACR 23 mg/mmol),他们主要患有糖尿病肾病和肾血管硬化。中位随访时间为 6.3 (3.3; 9.9) 年。与对照组-CKD相比,原发性肾小球疾病患者的住院、MACE(调整后危险比[HRs]为0.44至0.88,取决于病因)和死亡(HRs为0.45至0.76)风险普遍较低。IgAN和FSGS患者的eGFR下降更快,KRT率更高(HR分别为1.26 [95%CI:1.15-1.37] 和1.34 [1.15-1.57])。相反,MN 和 MCD 患者的 KRT 率较低,eGFR 下降较慢:结论:尽管IgAN和FSGS患者住院、心血管事件和死亡的相对风险较低,但与最常见的CKD病因相比,他们的CKD进展风险更高,因此需要对这些患者采取更严格的治疗策略。
{"title":"Primary glomerular diseases and long-term adverse health outcomes: A nationwide cohort study.","authors":"Anne-Laure Faucon, Stefania Lando, Charikleia Chrysostomou, Julia Wijkström, Sigrid Lundberg, Rino Bellocco, Mårten Segelmark, Marie Evans, Juan-Jesús Carrero","doi":"10.1111/joim.20024","DOIUrl":"https://doi.org/10.1111/joim.20024","url":null,"abstract":"<p><strong>Background: </strong>Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide, little is known about their long-term outcomes.</p><p><strong>Methods: </strong>In patients with chronic kidney disease (CKD) stage 3-5 enrolled in the Swedish Renal Registry, we compared risks of hospitalization, kidney replacement therapy (KRT), major cardiovascular events (MACE), and death of the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD], and membranous nephropathy [MN]), and patients with CKD due to the most common non-communicable diseases (control-CKD).</p><p><strong>Results: </strong>We identified 2396 patients with glomerular disease (97% biopsy-proven, 69% men, 57 years, eGFR 29 mL/min/1.73 m<sup>2</sup>, uACR 88 mg/mmol, 1524 with IgAN, 398 FSGS, 94 MCD, and 380 MN) and 37,697 controls (64% men, 74 years, eGFR 25 mL/min/1.73 m<sup>2</sup>, uACR 23 mg/mmol), mainly with diabetic nephropathy and nephroangiosclerosis. The median follow-up was 6.3 (3.3; 9.9) years. Compared with control-CKD, patients with primary glomerular diseases generally had a lower risk of hospitalization, MACE (adjusted hazard ratios [HRs] ranging from 0.44 to 0.88 depending on the etiology) and death (HRs ranging 0.45-0.76). Patients with IgAN and FSGS had a faster eGFR decline and a higher rate of KRT (HRs 1.26 [95%CI: 1.15-1.37] and 1.34 [1.15-1.57], respectively). Conversely, patients with MN and MCD had a lower KRT rate and slower eGFR decline.</p><p><strong>Conclusion: </strong>Despite having a lower relative risk of hospitalization, cardiovascular events and mortality, patients with IgAN and FSGS are at higher risk of CKD progression than the most common etiologies of CKD, emphasizing the need for more stringent treatment strategies in these patients.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613230","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}
引用次数: 0
Association among major adverse cardiovascular events with immune checkpoint inhibitors: A systematic review and meta-analysis. 免疫检查点抑制剂与主要心血管不良事件的关系:系统综述和荟萃分析。
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-13 DOI: 10.1111/joim.20028
Haixia Li, Yanfei Zheng, Bin Li, Yinghao Zhi, Mingxian Chen, Jing Zeng, Qian Jiao, Yuxuan Tao, Xinmei Liu, Zican Shen, Jiahui Zhang, Weizhe Zhao, Dong Chen

Background: This meta-analysis aimed to determine the incidence and overall risk of major adverse cardiovascular events (MACEs) related to immune checkpoint inhibitors (ICIs).

Methods: We systematically searched all cohort studies, including the available MACE data in cancer patients receiving ICIs, in PubMed, Embase, and the Cochrane Library, from their inception to September 5, 2023. The primary outcome was the incidence of MACEs associated with ICI exposure, and the secondary outcome was the overall risk of MACEs associated with ICI exposure versus non-ICI exposure controls. Risk ratios with 95% confidence intervals were used in the random- or fixed-effects models.

Results: Overall, 26 cohort studies met the inclusion criteria, involving 109,883 cancer patients. In the median follow-up period ranging from 3.3 to 55.2 months, the incidence of MACEs associated with ICI exposure was 8.22%, ranging from 0.55% to 3.98%, among the nine MACEs, including myocarditis, tachyarrhythmia, pericarditis, pericardial effusions, cardiovascular death, myocardial infarction, heart failure, stroke, and conduction disorder. The incidence of MACE associated with non-ICI exposure was 3.84%, ranging from 0.81% to 4.72%. The risks of all-grade MACEs and pericardial effusions were significantly higher in the ICI group than in the non-ICI controls. ICI treatment, age, male sex, and prior radiation therapy were significantly associated with MACEs.

Conclusion: The risk of MACEs during ICI treatment in patients with cancer is more common than is currently recognized. ICI use is closely associated with an increased risk of MACEs. Patients at risk were older, male, and had a history of radiation therapy.

背景这项荟萃分析旨在确定与免疫检查点抑制剂(ICIs)相关的主要不良心血管事件(MACEs)的发生率和总体风险:我们在PubMed、Embase和Cochrane图书馆中系统检索了从开始到2023年9月5日的所有队列研究,包括接受ICIs治疗的癌症患者的现有MACE数据。主要研究结果是与ICI暴露相关的MACE发生率,次要研究结果是ICI暴露与非ICI暴露对照相关的MACE总风险。随机效应或固定效应模型中使用了带有 95% 置信区间的风险比:共有 26 项队列研究符合纳入标准,涉及 109,883 名癌症患者。在3.3个月至55.2个月的中位随访期内,与ICI暴露相关的MACE发生率为8.22%,介于0.55%至3.98%之间,其中包括心肌炎、心动过速、心包炎、心包积液、心血管死亡、心肌梗死、心力衰竭、中风和传导障碍等9种MACE。与非心肌梗死相关的MACE发生率为3.84%,从0.81%到4.72%不等。ICI组患者发生所有级别MACE和心包积液的风险明显高于非ICI对照组。ICI治疗、年龄、男性和既往放疗与MACEs显著相关:结论:癌症患者在接受 ICI 治疗期间发生 MACEs 的风险比目前公认的更为常见。ICI 的使用与 MACEs 风险的增加密切相关。高危患者年龄较大,为男性,有放疗史。
{"title":"Association among major adverse cardiovascular events with immune checkpoint inhibitors: A systematic review and meta-analysis.","authors":"Haixia Li, Yanfei Zheng, Bin Li, Yinghao Zhi, Mingxian Chen, Jing Zeng, Qian Jiao, Yuxuan Tao, Xinmei Liu, Zican Shen, Jiahui Zhang, Weizhe Zhao, Dong Chen","doi":"10.1111/joim.20028","DOIUrl":"https://doi.org/10.1111/joim.20028","url":null,"abstract":"<p><strong>Background: </strong>This meta-analysis aimed to determine the incidence and overall risk of major adverse cardiovascular events (MACEs) related to immune checkpoint inhibitors (ICIs).</p><p><strong>Methods: </strong>We systematically searched all cohort studies, including the available MACE data in cancer patients receiving ICIs, in PubMed, Embase, and the Cochrane Library, from their inception to September 5, 2023. The primary outcome was the incidence of MACEs associated with ICI exposure, and the secondary outcome was the overall risk of MACEs associated with ICI exposure versus non-ICI exposure controls. Risk ratios with 95% confidence intervals were used in the random- or fixed-effects models.</p><p><strong>Results: </strong>Overall, 26 cohort studies met the inclusion criteria, involving 109,883 cancer patients. In the median follow-up period ranging from 3.3 to 55.2 months, the incidence of MACEs associated with ICI exposure was 8.22%, ranging from 0.55% to 3.98%, among the nine MACEs, including myocarditis, tachyarrhythmia, pericarditis, pericardial effusions, cardiovascular death, myocardial infarction, heart failure, stroke, and conduction disorder. The incidence of MACE associated with non-ICI exposure was 3.84%, ranging from 0.81% to 4.72%. The risks of all-grade MACEs and pericardial effusions were significantly higher in the ICI group than in the non-ICI controls. ICI treatment, age, male sex, and prior radiation therapy were significantly associated with MACEs.</p><p><strong>Conclusion: </strong>The risk of MACEs during ICI treatment in patients with cancer is more common than is currently recognized. ICI use is closely associated with an increased risk of MACEs. Patients at risk were older, male, and had a history of radiation therapy.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613221","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}
引用次数: 0
Incidence and predictors of clinical failure after early treatment for mild-to-moderate COVID-19 in high-risk individuals: A multicentric cohort study. 高危人群接受轻度至中度 COVID-19 早期治疗后临床失败的发生率和预测因素:多中心队列研究。
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-13 DOI: 10.1111/joim.20030
Ilaria Mastrorosa, Alessandro Cozzi Lepri, Cosmo Del Borgo, Silvia Rosati, Martina Rueca, Loredana Sarmati, Claudio Mastroianni, Massimo Fantoni, Fabrizio Maggi, Emanuele Nicastri, Enrico Girardi, Miriam Lichtner, Andrea Antinori, Valentina Mazzotta

Objectives: To estimate the risk of COVID-19-related hospitalization and death (CovH/D), among high-risk individuals early treated for COVID-19 and to identify associated factors.

Methods and results: A multicenter cohort of 12,475 high-risk outpatients (female 50.2%, median age 70 years [IQR 57-80], fully vaccinated 79.1%, immunocompromised 23.2%) treated with monoclonal antibodies or antivirals for mild-to-moderate COVID-19 (March 2021-May 2023) in the Lazio region, Italy. The unadjusted risk of CovH/D by Day 30 was 3.08% (95% CI 2.7%-3.4%). By means of logistic regression models, which included a specific set of potential confounders for each exposure of interest, we observed a higher risk for the elderly, unvaccinated and immunocompromised participants. Using the "Delta period" as a reference, a decreased risk was observed for Omicron waves.

Conclusions: Despite the administration of COVID-19 early treatment and the decreasing risk of CovH/D across the calendar periods, the elderly, the unvaccinated and the immunocompromised people remain at high risk of clinical progression.

目的:估计早期接受 COVID-19 治疗的高危人群中与 COVID-19 相关的住院和死亡风险(CovH/D),并确定相关因素:估算早期接受COVID-19治疗的高危人群中与COVID-19相关的住院和死亡风险(CovH/D),并确定相关因素:在意大利拉齐奥大区对12475名高风险门诊患者(女性占50.2%,中位年龄70岁[IQR 57-80],完全接种疫苗者占79.1%,免疫力低下者占23.2%)进行多中心队列研究,这些患者均接受过单克隆抗体或抗病毒药物治疗,以治疗轻度至中度COVID-19(2021年3月至2023年5月)。未经调整的第30天CovH/D风险为3.08%(95% CI为2.7%-3.4%)。通过逻辑回归模型,我们观察到老年人、未接种疫苗者和免疫力低下者的风险较高。以 "德尔塔期 "为参考,我们观察到欧米克隆波的风险有所降低:结论:尽管COVID-19可早期治疗,且CovH/D的风险在各日历期均有所降低,但老年人、未接种疫苗者和免疫力低下者的临床进展风险仍然很高。
{"title":"Incidence and predictors of clinical failure after early treatment for mild-to-moderate COVID-19 in high-risk individuals: A multicentric cohort study.","authors":"Ilaria Mastrorosa, Alessandro Cozzi Lepri, Cosmo Del Borgo, Silvia Rosati, Martina Rueca, Loredana Sarmati, Claudio Mastroianni, Massimo Fantoni, Fabrizio Maggi, Emanuele Nicastri, Enrico Girardi, Miriam Lichtner, Andrea Antinori, Valentina Mazzotta","doi":"10.1111/joim.20030","DOIUrl":"https://doi.org/10.1111/joim.20030","url":null,"abstract":"<p><strong>Objectives: </strong>To estimate the risk of COVID-19-related hospitalization and death (CovH/D), among high-risk individuals early treated for COVID-19 and to identify associated factors.</p><p><strong>Methods and results: </strong>A multicenter cohort of 12,475 high-risk outpatients (female 50.2%, median age 70 years [IQR 57-80], fully vaccinated 79.1%, immunocompromised 23.2%) treated with monoclonal antibodies or antivirals for mild-to-moderate COVID-19 (March 2021-May 2023) in the Lazio region, Italy. The unadjusted risk of CovH/D by Day 30 was 3.08% (95% CI 2.7%-3.4%). By means of logistic regression models, which included a specific set of potential confounders for each exposure of interest, we observed a higher risk for the elderly, unvaccinated and immunocompromised participants. Using the \"Delta period\" as a reference, a decreased risk was observed for Omicron waves.</p><p><strong>Conclusions: </strong>Despite the administration of COVID-19 early treatment and the decreasing risk of CovH/D across the calendar periods, the elderly, the unvaccinated and the immunocompromised people remain at high risk of clinical progression.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613223","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}
引用次数: 0
Lipoprotein(a) concentrations and cardiovascular disease in patients with chronic kidney disease: Results from the German Chronic Kidney Disease study 慢性肾病患者的脂蛋白(a)浓度与心血管疾病:德国慢性肾脏病研究结果。
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-08 DOI: 10.1111/joim.20027
Ida Gruber, Barbara Kollerits, Lukas Forer, Silvia Di Maio, Johanna F. Schachtl-Riess, Azin Kheirkhah, Sebastian Schönherr, Ulla T. Schultheiss, Anna Köttgen, Kai-Uwe Eckardt, Stefan Coassin, Claudia Lamina, Florian Kronenberg

Background

Lipoprotein(a) (Lp(a)) is a causal, genetically determined risk factor for cardiovascular disease (CVD) in the general population. Patients with chronic kidney disease (CKD) have an increased CVD risk and elevated Lp(a) concentrations. Only a few studies on Lp(a) were performed in persons with mild-to-moderate CKD; none of them used genetic variants to explore potential causal associations.

Objectives

This study aims to investigate the association of measured and genetically predicted Lp(a) concentrations on prevalent and incident CVD events in the German Chronic Kidney Disease (GCKD) study.

Methods

The study included 5043 participants of European ancestry with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2 or an eGFR >60 mL/min/1.73 m2 in the presence of overt albuminuria with a follow-up of 6.5 years.

Results

With each 10 mg/dL higher Lp(a) concentration, odds for prevalent CVD (1290 events) increased 1.065-fold (95%CI: 1.042–1.088, < 0.001). The risk was significantly higher in patients with Lp(a) ≥50 mg/dL but most pronounced in Lp(a) ≥70 mg/dL (odds ratio = 1.775 [1.409–2.231], < 0.001) compared to Lp(a) <30 mg/dL. Each 10 mg/dL higher Lp(a) concentration and Lp(a) ≥70 mg/dL increased the risk for incident 3-point major adverse cardiovascular events (MACEs) (474 events): hazard ratio [HR] = 1.037 [1.009–1.067], p = 0.009 and HR = 1.335 [1.001–1.781], p = 0.050), respectively. Similar results were obtained for 4-point MACE (653 events). Analyses based on apo(a) isoforms and genetically predicted Lp(a) concentrations led to even stronger associations.

Conclusions

In patients with mild-to-severe CKD, elevated Lp(a) concentrations and genetic determinants of Lp(a) concentrations are significantly associated with CVD at baseline and during follow-up, independent of traditional risk factors.

背景:脂蛋白(a)(Lp(a))是导致心血管疾病(CVD)的一个由基因决定的危险因素。慢性肾脏病(CKD)患者的心血管疾病风险增加,脂蛋白(a)浓度升高。只有少数几项关于脂蛋白(a)的研究是针对轻度至中度 CKD 患者进行的,其中没有一项研究使用基因变异来探讨潜在的因果关系:本研究旨在调查德国慢性肾脏病(GCKD)研究中测量的和基因预测的脂蛋白(a)浓度与心血管疾病发病率和发病率之间的关系:该研究纳入了5043名欧洲血统的参与者,他们的估计肾小球滤过率(eGFR)介于30至60 mL/min/1.73 m2之间,或eGFR >60 mL/min/1.73 m2且存在明显白蛋白尿,随访时间为6.5年:脂蛋白(a)浓度每升高10毫克/分升,心血管疾病(1290例)的发病几率就会增加1.065倍(95%CI:1.042-1.088,P在轻度至重度慢性肾脏病患者中,脂蛋白(a)浓度升高和脂蛋白(a)浓度的遗传决定因素与基线和随访期间的心血管疾病显著相关,不受传统风险因素的影响。
{"title":"Lipoprotein(a) concentrations and cardiovascular disease in patients with chronic kidney disease: Results from the German Chronic Kidney Disease study","authors":"Ida Gruber,&nbsp;Barbara Kollerits,&nbsp;Lukas Forer,&nbsp;Silvia Di Maio,&nbsp;Johanna F. Schachtl-Riess,&nbsp;Azin Kheirkhah,&nbsp;Sebastian Schönherr,&nbsp;Ulla T. Schultheiss,&nbsp;Anna Köttgen,&nbsp;Kai-Uwe Eckardt,&nbsp;Stefan Coassin,&nbsp;Claudia Lamina,&nbsp;Florian Kronenberg","doi":"10.1111/joim.20027","DOIUrl":"10.1111/joim.20027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lipoprotein(a) (Lp(a)) is a causal, genetically determined risk factor for cardiovascular disease (CVD) in the general population. Patients with chronic kidney disease (CKD) have an increased CVD risk and elevated Lp(a) concentrations. Only a few studies on Lp(a) were performed in persons with mild-to-moderate CKD; none of them used genetic variants to explore potential causal associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aims to investigate the association of measured and genetically predicted Lp(a) concentrations on prevalent and incident CVD events in the German Chronic Kidney Disease (GCKD) study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 5043 participants of European ancestry with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m<sup>2</sup> or an eGFR &gt;60 mL/min/1.73 m<sup>2</sup> in the presence of overt albuminuria with a follow-up of 6.5 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>With each 10 mg/dL higher Lp(a) concentration, odds for prevalent CVD (1290 events) increased 1.065-fold (95%CI: 1.042–1.088, <i>p </i>&lt; 0.001). The risk was significantly higher in patients with Lp(a) ≥50 mg/dL but most pronounced in Lp(a) ≥70 mg/dL (odds ratio = 1.775 [1.409–2.231], <i>p </i>&lt; 0.001) compared to Lp(a) &lt;30 mg/dL. Each 10 mg/dL higher Lp(a) concentration and Lp(a) ≥70 mg/dL increased the risk for incident 3-point major adverse cardiovascular events (MACEs) (474 events): hazard ratio [HR] = 1.037 [1.009–1.067], <i>p</i> = 0.009 and HR = 1.335 [1.001–1.781], <i>p</i> = 0.050), respectively. Similar results were obtained for 4-point MACE (653 events). Analyses based on apo(a) isoforms and genetically predicted Lp(a) concentrations led to even stronger associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with mild-to-severe CKD, elevated Lp(a) concentrations and genetic determinants of Lp(a) concentrations are significantly associated with CVD at baseline and during follow-up, independent of traditional risk factors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 6","pages":"510-526"},"PeriodicalIF":9.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regarding: Time to initiation of extracorporeal membrane oxygenation in conventional cardiopulmonary resuscitation affects the patient survival prognosis 关于:在常规心肺复苏术中启动体外膜肺氧合的时间会影响患者的生存预后。
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-10-24 DOI: 10.1111/joim.20022
Xiao Liu, Bo Liu, Minli Yang, Liu Yang, Jun Wang

The article by Sim et al. [1] in the Journal of Internal Medicine emphasized the critical role of timely ECMO application in optimizing outcomes for patients undergoing ECPR. While recognizing the careful work and valuable contributions of this study, there are some constructive suggestions for future advancement.

First, although the study accounted for various adjustment factors, it may have overlooked some potential influencing variables, such as patient comorbidities or changes in treatment protocols following ECMO initiation. These factors could affect the reliability and validity of the study's results [2].

Second, in the study, the Cox proportional hazards assumption may be violated for several reasons: time dependency: If the effect of ECMO initiation on survival varies over time, it breaches the assumption that hazard ratios remain constant throughout the study period; sample heterogeneity: Variability in patient characteristics within the sample may cause fluctuations in hazard ratios, thus violating the proportionality assumption; lack of testing: Without assessing the proportional hazards assumption using methods like Schoenfeld residuals, undetected violations could compromise the model's validity. Addressing these issues is crucial for ensuring the robustness and accuracy of the Cox regression analysis [3].

Third, the study primarily focuses on short-term outcomes (e.g., 30 days, 90 days, and 6 months), and there may be insufficient assessment of long-term survival and quality of life [4]. It is recommended that future research includes extended follow-up periods to obtain more comprehensive prognostic information.

In conclusion, the results of this study emphasize that the early initiation of ECMO during ECPR significantly improves short- and long-term overall survival outcomes. It highlights the need for prospective, multi-center research, long-term follow-up, standardized protocols, and optimization of procedures to improve clinical practices and patient survival.

Xiao Liu: Conceptualization; methodology; writing—original draft; validation. Bo Liu: Writing—review and editing. Minli Yang: Methodology; supervision. Liu Yang: Methodology; writing—review and editing. Jun Wang: Writing—review and editing; supervision.

The authors declare no conflicts of interest.

Sim 等人在《内科学杂志》上发表的文章[1]强调了及时应用 ECMO 对优化 ECPR 患者预后的关键作用。首先,尽管该研究考虑了各种调整因素,但可能忽略了一些潜在的影响变量,如患者的合并症或 ECMO 启动后治疗方案的变化。这些因素可能会影响研究结果的可靠性和有效性[2]。其次,在该研究中,由于以下几个原因,可能违反了 Cox 比例危险假设:时间依赖性:如果启动 ECMO 对存活率的影响随时间而变化,则违反了危险比在整个研究期间保持不变的假设;样本异质性:样本中患者特征的差异可能会导致危险比的波动,从而违反比例假设;缺乏检验:如果不使用 Schoenfeld residuals 等方法评估比例危险假设,未发现的违规行为可能会影响模型的有效性。解决这些问题对于确保 Cox 回归分析的稳健性和准确性至关重要[3]。第三,该研究主要关注短期结果(如 30 天、90 天和 6 个月),对长期生存和生活质量的评估可能不足[4]。总之,本研究结果强调,在 ECPR 期间尽早启动 ECMO 可显著改善短期和长期总体生存结果。该研究强调了前瞻性多中心研究、长期随访、标准化方案和优化程序的必要性,以改善临床实践和患者生存。刘波:写作-审稿和编辑。杨敏莉方法学;指导。杨柳方法学;写作-审阅和编辑。王军作者声明无利益冲突。
{"title":"Regarding: Time to initiation of extracorporeal membrane oxygenation in conventional cardiopulmonary resuscitation affects the patient survival prognosis","authors":"Xiao Liu,&nbsp;Bo Liu,&nbsp;Minli Yang,&nbsp;Liu Yang,&nbsp;Jun Wang","doi":"10.1111/joim.20022","DOIUrl":"10.1111/joim.20022","url":null,"abstract":"<p>The article by Sim et al. [<span>1</span>] in the <i>Journal of Internal Medicine</i> emphasized the critical role of timely ECMO application in optimizing outcomes for patients undergoing ECPR. While recognizing the careful work and valuable contributions of this study, there are some constructive suggestions for future advancement.</p><p>First, although the study accounted for various adjustment factors, it may have overlooked some potential influencing variables, such as patient comorbidities or changes in treatment protocols following ECMO initiation. These factors could affect the reliability and validity of the study's results [<span>2</span>].</p><p>Second, in the study, the Cox proportional hazards assumption may be violated for several reasons: time dependency: If the effect of ECMO initiation on survival varies over time, it breaches the assumption that hazard ratios remain constant throughout the study period; sample heterogeneity: Variability in patient characteristics within the sample may cause fluctuations in hazard ratios, thus violating the proportionality assumption; lack of testing: Without assessing the proportional hazards assumption using methods like Schoenfeld residuals, undetected violations could compromise the model's validity. Addressing these issues is crucial for ensuring the robustness and accuracy of the Cox regression analysis [<span>3</span>].</p><p>Third, the study primarily focuses on short-term outcomes (e.g., 30 days, 90 days, and 6 months), and there may be insufficient assessment of long-term survival and quality of life [<span>4</span>]. It is recommended that future research includes extended follow-up periods to obtain more comprehensive prognostic information.</p><p>In conclusion, the results of this study emphasize that the early initiation of ECMO during ECPR significantly improves short- and long-term overall survival outcomes. It highlights the need for prospective, multi-center research, long-term follow-up, standardized protocols, and optimization of procedures to improve clinical practices and patient survival.</p><p><b>Xiao Liu</b>: Conceptualization; methodology; writing—original draft; validation. <b>Bo Liu</b>: Writing—review and editing. <b>Minli Yang</b>: Methodology; supervision. <b>Liu Yang</b>: Methodology; writing—review and editing. <b>Jun Wang</b>: Writing—review and editing; supervision.</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 6","pages":"535-536"},"PeriodicalIF":9.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regarding: Time to initiation of extracorporeal membrane oxygenation in conventional cardiopulmonary resuscitation affects the patient survival prognosis 关于:在常规心肺复苏术中启动体外膜肺氧合的时间会影响患者的生存预后。
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-10-24 DOI: 10.1111/joim.20021
Wei-Zhen Tang, Zhe-Ming Kang, Tai-Hang Liu
<p>After a thorough analysis of the study by Ji-Hoon Sim et al., published in the <i>Journal of Internal Medicine</i>, we express our appreciation for their findings that the early initiation of extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (CPR) significantly improves short- and long-term survival outcomes. The study highlights the critical role of timely ECMO application in enhancing treatment results for patients receiving extracorporeal PCR (ECPR) [<span>1</span>]. Nevertheless, we believe there are several key issues within the study that could impact the interpretation of the results.</p><p>First, the exclusion criteria of the study did not specifically mention whether certain populations that could significantly affect the study conclusions were excluded. These include patients over the age of 75, those with end-stage malignancies, those requiring ongoing life support, patients with cardiac tamponade due to aortic dissection, and those with persistent intracranial hemorrhage or severe brain injury [<span>2</span>]. For instance, elderly patients may have different physiological characteristics and disease risks, which could affect their response to treatment and recovery capabilities compared to younger patients. The overall health status and life expectancy of patients with end-stage malignancies are already severely compromised. If these patients were not properly excluded, their inclusion could lower overall survival rates, thereby affecting the assessment of ECMO efficacy. Patients who required continuous life support prior to cardiac arrest may have a poorer baseline health status, which could influence the accuracy of the study's findings regarding the relationship between the timing of ECMO initiation and survival rates.</p><p>Second, although the study distinguished between out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest patients, it did not detail whether key pre-hospital characteristics of OHCA patients were recorded [<span>2</span>]. Such characteristics include the time of collapse, the presence of a witness, bystander CPR, the occurrence of transient return of spontaneous circulation before hospital arrival, initial shockable rhythm, and the interval from collapse to the initiation of CPR. Pre-hospital constraints may delay the start of ECMO, thereby prolonging the duration of low blood flow in patients, affecting organ perfusion and, ultimately, prognosis [<span>3</span>]. Moreover, the ECMO outcomes for OHCA patients may be affected by the quality of emergency medical services and pre-hospital treatment systems. The difficulty of manual CPR during ambulance transport suggests that mechanical CPR before the start of ECMO could yield different survival outcomes. The lack of these data could limit a comprehensive understanding of the pre-hospital situation and resuscitation process for OHCA patients, which is crucial for analysing the impact of the CPR-to-ECMO interval on p
经过对 Ji-Hoon Sim 等人发表在《内科学杂志》(Journal of Internal Medicine)上的研究进行深入分析,我们对他们的研究结果表示赞赏,即在心肺复苏(CPR)期间尽早启动体外膜肺氧合(ECMO)可显著改善短期和长期生存结果。该研究强调了及时应用 ECMO 对提高接受体外 PCR(ECPR)患者治疗效果的关键作用[1]。然而,我们认为该研究中存在几个关键问题,可能会影响对结果的解释。首先,该研究的排除标准没有具体提及是否排除了某些可能对研究结论产生重大影响的人群。这些人群包括 75 岁以上的患者、恶性肿瘤晚期患者、需要持续生命支持的患者、主动脉夹层导致心脏填塞的患者以及颅内持续出血或严重脑损伤的患者[2]。例如,与年轻患者相比,老年患者可能具有不同的生理特点和疾病风险,这可能会影响他们对治疗的反应和康复能力。晚期恶性肿瘤患者的整体健康状态和预期寿命已经受到严重影响。如果不适当地将这些患者排除在外,他们的加入可能会降低总体存活率,从而影响 ECMO 疗效的评估。其次,尽管该研究区分了院外心脏骤停(OHCA)和院内心脏骤停患者,但并未详细说明是否记录了 OHCA 患者院前的关键特征[2]。这些特征包括倒地时间、有无目击者、旁观者心肺复苏、到达医院前是否出现短暂的自主循环恢复、初始可电击心律以及从倒地到开始心肺复苏的时间间隔。院前限制因素可能会延迟 ECMO 的启动,从而延长患者低血流的持续时间,影响器官灌注,最终影响预后[3]。此外,急诊医疗服务和院前治疗系统的质量也会影响 OHCA 患者的 ECMO 治疗效果。救护车转运过程中人工心肺复苏的困难表明,在开始 ECMO 之前进行机械心肺复苏可能会产生不同的生存结果。这些数据的缺乏可能会限制对 OHCA 患者院前情况和复苏过程的全面了解,而这对于分析心肺复苏到 ECMO 的时间间隔对预后的影响至关重要。最后,该研究没有提及心脏骤停后护理的具体细节,如输血、呼吸机设置和感染性并发症的治疗。这些护理措施通常是心脏骤停后患者综合治疗和管理的重要组成部分,对患者的恢复和预后有重大影响。此外,该研究没有记录 ECMO 治疗开始后的重要观察指标,如早期达到平均动脉压、治疗性体温管理、ECMO 后左心室射血分数、体外生命支持的成功断流以及 ECMO 期间的并发症,包括通路部位出血、肢体缺血和颅内出血。这些因素已被证明是影响 ECMO 预后的重要因素[4]。总之,尽管辛智勋等人的研究结论具有启发性,但只有进一步分析并解决上述问题,才能提高研究结论的可信度和实用性:概念化;方法;验证。康哲明:概念化;验证;可视化;形式分析。刘太行:形式分析;调查。作者声明无利益冲突。
{"title":"Regarding: Time to initiation of extracorporeal membrane oxygenation in conventional cardiopulmonary resuscitation affects the patient survival prognosis","authors":"Wei-Zhen Tang,&nbsp;Zhe-Ming Kang,&nbsp;Tai-Hang Liu","doi":"10.1111/joim.20021","DOIUrl":"10.1111/joim.20021","url":null,"abstract":"&lt;p&gt;After a thorough analysis of the study by Ji-Hoon Sim et al., published in the &lt;i&gt;Journal of Internal Medicine&lt;/i&gt;, we express our appreciation for their findings that the early initiation of extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (CPR) significantly improves short- and long-term survival outcomes. The study highlights the critical role of timely ECMO application in enhancing treatment results for patients receiving extracorporeal PCR (ECPR) [&lt;span&gt;1&lt;/span&gt;]. Nevertheless, we believe there are several key issues within the study that could impact the interpretation of the results.&lt;/p&gt;&lt;p&gt;First, the exclusion criteria of the study did not specifically mention whether certain populations that could significantly affect the study conclusions were excluded. These include patients over the age of 75, those with end-stage malignancies, those requiring ongoing life support, patients with cardiac tamponade due to aortic dissection, and those with persistent intracranial hemorrhage or severe brain injury [&lt;span&gt;2&lt;/span&gt;]. For instance, elderly patients may have different physiological characteristics and disease risks, which could affect their response to treatment and recovery capabilities compared to younger patients. The overall health status and life expectancy of patients with end-stage malignancies are already severely compromised. If these patients were not properly excluded, their inclusion could lower overall survival rates, thereby affecting the assessment of ECMO efficacy. Patients who required continuous life support prior to cardiac arrest may have a poorer baseline health status, which could influence the accuracy of the study's findings regarding the relationship between the timing of ECMO initiation and survival rates.&lt;/p&gt;&lt;p&gt;Second, although the study distinguished between out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest patients, it did not detail whether key pre-hospital characteristics of OHCA patients were recorded [&lt;span&gt;2&lt;/span&gt;]. Such characteristics include the time of collapse, the presence of a witness, bystander CPR, the occurrence of transient return of spontaneous circulation before hospital arrival, initial shockable rhythm, and the interval from collapse to the initiation of CPR. Pre-hospital constraints may delay the start of ECMO, thereby prolonging the duration of low blood flow in patients, affecting organ perfusion and, ultimately, prognosis [&lt;span&gt;3&lt;/span&gt;]. Moreover, the ECMO outcomes for OHCA patients may be affected by the quality of emergency medical services and pre-hospital treatment systems. The difficulty of manual CPR during ambulance transport suggests that mechanical CPR before the start of ECMO could yield different survival outcomes. The lack of these data could limit a comprehensive understanding of the pre-hospital situation and resuscitation process for OHCA patients, which is crucial for analysing the impact of the CPR-to-ECMO interval on p","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 6","pages":"533-534"},"PeriodicalIF":9.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Authors reply: Time to initiation of extracorporeal membrane oxygenation in conventional cardiopulmonary resuscitation affects the patient survival prognosis 作者回复:在常规心肺复苏中启动体外膜肺氧合的时间会影响患者的生存预后。
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-10-24 DOI: 10.1111/joim.20023
Sang-Wook Lee, Ji-Hoon Sim
<p>We appreciate the opportunity to respond to the three Letters to the Editor [<span>1-3</span>] commenting on our article [<span>4</span>], published in the <i>Journal of Internal Medicine</i>. We have carefully discussed them with the respective authors. We want to express our sincere gratitude for their interest in our work and for the valuable suggestions they have provided.</p><p>First, we would like to address the concern raised in all three letters regarding the absence of clear exclusion criteria for comorbidities in our study group [<span>4, 5</span>]. We fully acknowledge and agree with the points raised by the authors of the letters. Although we share their concerns, our study was based on a retrospective data analysis. Consequently, we opted to address these effects by applying statistical corrections in a multivariate analysis rather than excluding them from our study altogether. We agree that in future prospective studies on this topic, it is indeed crucial to thoroughly consider and incorporate multiple factors that may influence patient outcomes into the exclusion criteria.</p><p>Second, we would like to address their comments regarding the significant prehospital characteristics of out-of-hospital cardiac arrest (OHCA) patients highlighted in the study. We concur with the authors that there are numerous factors specific to OHCA patients, as opposed to in-hospital cardiac arrest (IHCA) patients, that can influence outcomes [<span>6</span>]. Indeed, it may be more effective to analyse OHCA patients separately from IHCA patients to reach more definitive conclusions. OHCA patients often face more challenges that can delay extracorporeal membrane oxygenation (ECMO) initiation, and in our data, these factors were associated with a poorer prognosis compared to IHCA patients. In future research, it would be advantageous to analyse OHCA patients separately from IHCA patients using a larger dataset to derive clearer insights on these issues.</p><p>Third, we would like to comment on the issues raised by the authors regarding the specific details of post-cardiac arrest care. We agree that various post-cardiac arrest interventions—such as blood transfusions, ventilator settings, treatment of infectious complications, and therapeutic temperature management—as well as complications occurring during ECMO, such as insertion site bleeding, limb ischemia, and intracranial hemorrhage, are critical factors that impact the prognosis of cardiac arrest patients [<span>7, 8</span>]. Unfortunately, our study lacked sufficient data in this area to present detailed results. We recognize that detailed descriptions of these post-cardiac arrest treatments and complications may be crucial in understanding the prognosis of ECPR patients, and future studies should include these details and better assess their impact on outcomes.</p><p>Finally, we would like to respond to the point raised by the authors regarding the insufficient evaluation of long-term outcomes
我们很高兴有机会对发表在《内科学杂志》上的三封评论我们的文章[4]的致编辑信[1-3]做出回应。我们与相关作者进行了认真讨论。首先,我们想回应三封来信中提出的关于我们的研究小组缺乏明确的合并症排除标准的担忧[4, 5]。我们完全承认并同意作者们在信中提出的观点。虽然我们也有同感,但我们的研究是基于回顾性数据分析。因此,我们选择在多变量分析中应用统计校正来解决这些影响,而不是将其完全排除在我们的研究之外。我们同意,在未来有关该主题的前瞻性研究中,将可能影响患者预后的多种因素全面考虑并纳入排除标准确实至关重要。其次,我们想谈谈作者对研究中强调的院外心脏骤停(OHCA)患者院前重要特征的看法。我们同意作者的观点,即与院内心脏骤停(IHCA)患者相比,院外心脏骤停患者有许多特殊因素会影响预后[6]。事实上,将 OHCA 患者与 IHCA 患者分开分析可能会更有效,从而得出更明确的结论。与 IHCA 患者相比,OHCA 患者往往面临着更多的挑战,这些挑战可能会延迟体外膜肺氧合(ECMO)的启动,在我们的数据中,这些因素与较差的预后相关。在未来的研究中,最好使用更大的数据集将 OHCA 患者与 IHCA 患者分开分析,以便更清楚地了解这些问题。第三,我们想就作者提出的有关心脏骤停后护理具体细节的问题发表评论。我们同意,心脏骤停后的各种干预措施,如输血、呼吸机设置、感染性并发症治疗和治疗性体温管理,以及 ECMO 期间发生的并发症,如插入部位出血、肢体缺血和颅内出血,都是影响心脏骤停患者预后的关键因素[7, 8]。遗憾的是,我们的研究在这方面缺乏足够的数据,无法提供详细的结果。我们认识到,详细描述这些心脏骤停后的治疗和并发症可能对了解 ECPR 患者的预后至关重要,未来的研究应包括这些细节,并更好地评估它们对预后的影响。最后,我们想对作者提出的关于 6 个月后长期预后评估不足的观点做出回应[6]。为了将尽可能多的 ECPR 患者纳入我们的研究,我们分析了近期接受 ECPR 的患者的数据,因此观察期相对较短,约为 6 个月。我们同意,较短的观察期可能限制了我们评估 6 个月后长期结果的能力。在未来的研究中,我们认为对患者进行 1 年或更长时间的随访结果分析将非常有价值。尽管作者指出了许多局限性,但我们认为我们的研究在强调对心脏骤停患者进行及时 ECMO 干预的重要性方面意义重大。我们相信,随着 ECPR 数据的不断增加,更高质量的分析将有助于澄清一些未知问题。最后,我们对审稿人对我们研究的关注和提出的宝贵意见深表感谢。Sang-Wook Lee:写作-原稿;构思;写作-审阅和编辑;调查。Ji-Hoon Sim:作者声明无利益冲突。
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引用次数: 0
期刊
Journal of Internal Medicine
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