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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, the Early Treatment for COVID-19 Lazio Study Group

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。
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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。
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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。
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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。
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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
Increased risk of hypereosinophilia following initiation of glucagon-like peptide 1 receptor agonist: A symmetry analysis using the Danish health registries 开始服用胰高血糖素样肽 1 受体激动剂后嗜酸性粒细胞增多症的风险增加:利用丹麦健康登记进行的对称性分析。
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-10-23 DOI: 10.1111/joim.20025
Martin Torp Rahbek, Søren Andreas Just, Kasper Bruun Kristensen, Hussam Mahmoud Sheta, Jesper Hallas, Anton Pottegård, Lars Christian Lund
<p>Glucagon-like peptide 1 receptor agonists (GLP1-RA) are increasingly used in the treatment of Type 2 diabetes and as antiobesity drugs. Cases of hypereosinophilic syndrome (HES) following initiation of GLP1-RA have been reported [<span>1</span>]. HES is defined by eosinophil counts of 1.5 × 10<sup>9</sup>/L or greater and related end-organ damage [<span>2</span>]. Because these events are too rare to be detected in randomized controlled trials, we aimed to quantify the association between GLP1-RA initiation and incident hypereosinophilia (HE) using real-world data.</p><p>Leveraging nationwide Danish prescription [<span>3</span>] and laboratory data [<span>4</span>], we conducted a sequence symmetry analysis (SSA) investigating the occurrence of HE following initiation of GLP1-RA and for comparison sodium–glucose co-transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase 4 inhibitors (DPP4i) [<span>5</span>].</p><p>The SSA compares the occurrence of HE during a symmetric time window before and after initiation of the drug of interest. If there is no association between drug initiation and HE, we would expect HE to occur equally often during both windows. However, if GLP1-RA use increases eosinophil counts, we would expect HE to occur more frequently after initiation. The sequence ratio (SR) is calculated as the number of HE events after drug initiation divided by the number of HE events before drug initiation and corresponds to the incidence rate ratio obtained in the corresponding cohort study [<span>6</span>]. If the rate of HE is increased after initiation of GLP1-RA compared to the period before initiation, we would expect an SR above 1.</p><p>We identified all individuals who initiated a GLP1-RA, SGLT2i or DPP4i (Appendix) between 1 June 2015 and 31 May 2024 and obtained eosinophil counts of 1.5 × 10<sup>9</sup>/L or greater within the last 180 days before the drug initiation, or within the first 180 days after. Observed SRs were adjusted for temporal trends in HE [<span>5</span>]. In subgroup analyses, we evaluated semaglutide and other GLP1-RAs separately, as well as Ozempic and Wegovy. For sensitivity analyses, we calculated SRs for observation windows of 90 and 365 days and with mild (≥0.5–1.5 × 10<sup>9</sup>/L) and massive eosinophilia (≥5 × 10<sup>9</sup>/L) as outcomes. Finally, we used a thrombocyte count below 50 × 10<sup>9</sup>/L as a negative control outcome.</p><p>The study was approved by the institutional data protection board at the University of Southern Denmark and the Danish Health Data Authority (Project number FSEID-00006047). Ethical approval is not needed in Denmark for studies based purely on registry data.</p><p>We identified 213,521 individuals who initiated a GLP1-RA among whom 245 had HE within 1 year of drug initiation. The median age was 54 years (interquartile range [IQR] 42–63), 49% were female and median year of initiation of GLP1-RA was 2022 (IQR 2021–2023<i>)</i>. Of these, 193 individuals had HE afte
胰高血糖素样肽 1 受体激动剂(GLP1-RA)越来越多地用于治疗 2 型糖尿病和作为抗肥胖药物。有报道称,开始使用 GLP1-RA 后出现了嗜酸性粒细胞过多综合征(HES)病例 [1]。嗜酸性粒细胞过多综合征的定义是嗜酸性粒细胞计数达到或超过 1.5 × 109/L 以及相关的内脏器官损伤[2]。由于这些事件过于罕见,无法在随机对照试验中检测到,因此我们旨在利用真实世界的数据来量化 GLP1-RA 启动与嗜酸性粒细胞过多症(HE)事件之间的关联。利用丹麦全国范围内的处方[3]和实验室数据[4],我们进行了序列对称性分析(SSA),调查开始服用 GLP1-RA 以及钠-葡萄糖协同转运体 2 抑制剂(SGLT2i)和二肽基肽酶 4 抑制剂(DPP4i)[5]后嗜酸性粒细胞增多症的发生情况。如果开始用药与高血压之间没有关联,我们预计高血压在两个时间窗内发生的频率相同。但是,如果使用 GLP1-RA 会增加嗜酸性粒细胞的数量,我们就会认为在开始用药后嗜酸性粒细胞增多的发生率会更高。序列比(SR)的计算方法是用开始用药后的 HE 事件数除以开始用药前的 HE 事件数,并与相应队列研究中获得的发病率比值相对应[6]。我们确定了在 2015 年 6 月 1 日至 2024 年 5 月 31 日期间开始使用 GLP1-RA、SGLT2i 或 DPP4i(附录),且在开始用药前最后 180 天内或用药后最初 180 天内嗜酸性粒细胞计数达到或超过 1.5 × 109/L 的所有患者。观察到的 SR 根据 HE 的时间趋势进行了调整 [5]。在亚组分析中,我们分别评估了semaglutide和其他GLP1-RA,以及Ozempic和Wegovy。在敏感性分析中,我们计算了 90 天和 365 天观察窗的 SR,并将轻度(≥0.5-1.5 × 109/L)和大量嗜酸性粒细胞增多(≥5 × 109/L)作为结果。最后,我们将血小板计数低于 50 × 109/L 作为阴性对照结果。该研究获得了南丹麦大学机构数据保护委员会和丹麦健康数据管理局的批准(项目编号 FSEID-00006047)。在丹麦,纯粹基于登记数据的研究不需要伦理批准。我们确定了 213,521 名开始服用 GLP1-RA 的患者,其中 245 人在开始服药后 1 年内出现高血压。年龄中位数为 54 岁(四分位数间距 [IQR] 42-63),49% 为女性,开始服用 GLP1-RA 的年份中位数为 2022 年(IQR 2021-2023)。其中,193 人在开始用药后出现高血压,52 人在开始用药前出现高血压,SR 为 3.83(95% 置信区间 [CI] 2.84-5.24)。在亚组分析中,semaglutide、其他 GLP1-RA、Wegovy 和 Ozempic 的 SR 与所有 GLP1-RA 合并的结果相似(图 1)。轻度嗜酸性粒细胞增多结果显示,GLP1-RA 启动者的 SR 为 1.08(N = 1207/1136,CI 1.0-1.18)。对于大量嗜酸性粒细胞增多,我们观察到 GLP1-RA 启动后发生了 13 起事件,而启动前发生的事件不到 5 起。对较短和较长的观察窗口进行分析后,发现SRs升高(SR为3.87,CI为2.62-5.85和2.50 [1.97-3.18])。对于阴性对照结果,我们发现 GLP1-RA、SGLT2i 和 DPP4i 的 SR 分别为 1.64(N = 44/27,CI 1.02-2.66)、1.28(N = 118/93,CI 0.98-1.68)和 0.84(N = 75/89,CI 0.62-1.15)。图 S1 显示,在开始使用 GLP1-RA 后的前 3 个月,HE 的发病率急剧上升,而在开始使用 SGLT2i 或 DPP4i 的患者中未观察到这一现象。这一发现仅针对 GLP1-RAs,在其他抗糖尿病药物中并未观察到。尽管阴性对照结果对 GLP1-RAs 而言并非无效,但与主要分析结果相比,阴性对照结果更接近于 1.0,并且与 SGLT2i 的结果一致。因此,我们的研究为 GLP1-RAs 的启动与 HE 之间的时间关联提供了证据。我们研究的主要局限性在于,研究结果是生化定义的高血压,而不是高血压导致的内脏损害。另一个重要的局限性是,研究对象只包括开始服用 GLP1-RA 并测量了嗜酸性粒细胞计数的人。需要进行更大规模的研究,以量化GLP1-RA与临床表现的HES之间的潜在关联。
{"title":"Increased risk of hypereosinophilia following initiation of glucagon-like peptide 1 receptor agonist: A symmetry analysis using the Danish health registries","authors":"Martin Torp Rahbek,&nbsp;Søren Andreas Just,&nbsp;Kasper Bruun Kristensen,&nbsp;Hussam Mahmoud Sheta,&nbsp;Jesper Hallas,&nbsp;Anton Pottegård,&nbsp;Lars Christian Lund","doi":"10.1111/joim.20025","DOIUrl":"10.1111/joim.20025","url":null,"abstract":"&lt;p&gt;Glucagon-like peptide 1 receptor agonists (GLP1-RA) are increasingly used in the treatment of Type 2 diabetes and as antiobesity drugs. Cases of hypereosinophilic syndrome (HES) following initiation of GLP1-RA have been reported [&lt;span&gt;1&lt;/span&gt;]. HES is defined by eosinophil counts of 1.5 × 10&lt;sup&gt;9&lt;/sup&gt;/L or greater and related end-organ damage [&lt;span&gt;2&lt;/span&gt;]. Because these events are too rare to be detected in randomized controlled trials, we aimed to quantify the association between GLP1-RA initiation and incident hypereosinophilia (HE) using real-world data.&lt;/p&gt;&lt;p&gt;Leveraging nationwide Danish prescription [&lt;span&gt;3&lt;/span&gt;] and laboratory data [&lt;span&gt;4&lt;/span&gt;], we conducted a sequence symmetry analysis (SSA) investigating the occurrence of HE following initiation of GLP1-RA and for comparison sodium–glucose co-transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase 4 inhibitors (DPP4i) [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The SSA compares the occurrence of HE during a symmetric time window before and after initiation of the drug of interest. If there is no association between drug initiation and HE, we would expect HE to occur equally often during both windows. However, if GLP1-RA use increases eosinophil counts, we would expect HE to occur more frequently after initiation. The sequence ratio (SR) is calculated as the number of HE events after drug initiation divided by the number of HE events before drug initiation and corresponds to the incidence rate ratio obtained in the corresponding cohort study [&lt;span&gt;6&lt;/span&gt;]. If the rate of HE is increased after initiation of GLP1-RA compared to the period before initiation, we would expect an SR above 1.&lt;/p&gt;&lt;p&gt;We identified all individuals who initiated a GLP1-RA, SGLT2i or DPP4i (Appendix) between 1 June 2015 and 31 May 2024 and obtained eosinophil counts of 1.5 × 10&lt;sup&gt;9&lt;/sup&gt;/L or greater within the last 180 days before the drug initiation, or within the first 180 days after. Observed SRs were adjusted for temporal trends in HE [&lt;span&gt;5&lt;/span&gt;]. In subgroup analyses, we evaluated semaglutide and other GLP1-RAs separately, as well as Ozempic and Wegovy. For sensitivity analyses, we calculated SRs for observation windows of 90 and 365 days and with mild (≥0.5–1.5 × 10&lt;sup&gt;9&lt;/sup&gt;/L) and massive eosinophilia (≥5 × 10&lt;sup&gt;9&lt;/sup&gt;/L) as outcomes. Finally, we used a thrombocyte count below 50 × 10&lt;sup&gt;9&lt;/sup&gt;/L as a negative control outcome.&lt;/p&gt;&lt;p&gt;The study was approved by the institutional data protection board at the University of Southern Denmark and the Danish Health Data Authority (Project number FSEID-00006047). Ethical approval is not needed in Denmark for studies based purely on registry data.&lt;/p&gt;&lt;p&gt;We identified 213,521 individuals who initiated a GLP1-RA among whom 245 had HE within 1 year of drug initiation. The median age was 54 years (interquartile range [IQR] 42–63), 49% were female and median year of initiation of GLP1-RA was 2022 (IQR 2021–2023&lt;i&gt;)&lt;/i&gt;. Of these, 193 individuals had HE afte","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 6","pages":"527-530"},"PeriodicalIF":9.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491708","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 : 2024-10-23 DOI: 10.1111/joim.20020
Zegang Ruan, Yuhao Gan, Chenyang Xu

Dear Editor,

We read with great interest the article by Sim et al. [1] published in the Journal of Internal Medicine. The authors conducted a retrospective study involving 198 patients to examine the impact of extracorporeal membrane oxygenation (ECMO) initiation timing during routine cardiopulmonary resuscitation (CPR) on patient survival prognosis. The study's findings underscore the crucial role of ECMO in routine CPR, particularly highlighting that an early initiation of ECMO significantly enhances patient survival outcomes. We commend the authors for optimizing the timing of ECMO initiation in clinical practice. However, several aspects warrant further discussion.

First, the article selectively analysed patients who received ECMO but did not provide detailed information regarding the exclusion and selection criteria. For instance, there is no clear explanation of how patients with severe comorbidities or a higher risk of death were managed. This omission could result in a non-representative sample, potentially affecting the generalizability of the study's conclusions.

Second, the article inadequately addresses the neurological prognosis of the patients, as it fails to include data on their long-term neurological outcomes post-discharge (after 3 or 6 months). Given that neurological recovery following cardiac arrest may take an extended period [2], this limitation hinders a comprehensive understanding of the patient's long-term prognosis.

Third, although the article focuses on the timing of ECMO initiation, it does not analyse other concurrent treatments (e.g., high-quality CPR, medications, and temperature management) compared to ECMO. This omission prevents a clear delineation of ECMO's unique contribution relative to other interventions throughout the treatment process [3].

In conclusion, we appreciate the authors for highlighting the significance of timely ECMO initiation during CPR to improve patient survival. This work will raise healthcare professionals’ awareness of the critical importance of early ECMO initiation and contribute to the rapid advancement of this field.

Zegang Ruan: Methodology; writing—original draft; investigation. Yuhao Gan: Methodology; writing—original draft; investigation. Chenyang Xu: Writing—review and editing; supervision.

The authors declare no conflicts of interest.

亲爱的编辑,我们饶有兴趣地阅读了 Sim 等人发表在《内科学杂志》上的文章[1]。作者进行了一项涉及 198 名患者的回顾性研究,探讨了常规心肺复苏(CPR)过程中体外膜肺氧合(ECMO)启动时机对患者存活预后的影响。研究结果强调了 ECMO 在常规心肺复苏中的关键作用,尤其突出了尽早启动 ECMO 能显著提高患者的生存预后。我们对作者在临床实践中优化 ECMO 启动时机的做法表示赞赏。首先,文章选择性地分析了接受 ECMO 的患者,但没有提供有关排除和选择标准的详细信息。例如,文章没有明确解释如何管理合并症严重或死亡风险较高的患者。其次,文章对患者神经系统预后的描述不够充分,没有包括患者出院后(3 个月或 6 个月后)神经系统长期预后的数据。鉴于心脏骤停后神经功能的恢复可能需要较长的时间[2],这一局限性妨碍了对患者长期预后的全面了解。第三,尽管文章重点关注 ECMO 的启动时机,但并未分析与 ECMO 相比的其他并发治疗(如高质量心肺复苏、药物和体温管理)。总之,我们感谢作者强调在心肺复苏期间及时启动 ECMO 对提高患者存活率的重要意义。这项工作将提高医护人员对早期启动 ECMO 关键重要性的认识,并促进该领域的快速发展:方法学;写作-原稿;调查。甘宇豪方法学;写作-原稿;调查。徐晨阳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":"Zegang Ruan,&nbsp;Yuhao Gan,&nbsp;Chenyang Xu","doi":"10.1111/joim.20020","DOIUrl":"10.1111/joim.20020","url":null,"abstract":"<p>Dear Editor,</p><p>We read with great interest the article by Sim et al. [<span>1</span>] published in the <i>Journal of Internal Medicine</i>. The authors conducted a retrospective study involving 198 patients to examine the impact of extracorporeal membrane oxygenation (ECMO) initiation timing during routine cardiopulmonary resuscitation (CPR) on patient survival prognosis. The study's findings underscore the crucial role of ECMO in routine CPR, particularly highlighting that an early initiation of ECMO significantly enhances patient survival outcomes. We commend the authors for optimizing the timing of ECMO initiation in clinical practice. However, several aspects warrant further discussion.</p><p>First, the article selectively analysed patients who received ECMO but did not provide detailed information regarding the exclusion and selection criteria. For instance, there is no clear explanation of how patients with severe comorbidities or a higher risk of death were managed. This omission could result in a non-representative sample, potentially affecting the generalizability of the study's conclusions.</p><p>Second, the article inadequately addresses the neurological prognosis of the patients, as it fails to include data on their long-term neurological outcomes post-discharge (after 3 or 6 months). Given that neurological recovery following cardiac arrest may take an extended period [<span>2</span>], this limitation hinders a comprehensive understanding of the patient's long-term prognosis.</p><p>Third, although the article focuses on the timing of ECMO initiation, it does not analyse other concurrent treatments (e.g., high-quality CPR, medications, and temperature management) compared to ECMO. This omission prevents a clear delineation of ECMO's unique contribution relative to other interventions throughout the treatment process [<span>3</span>].</p><p>In conclusion, we appreciate the authors for highlighting the significance of timely ECMO initiation during CPR to improve patient survival. This work will raise healthcare professionals’ awareness of the critical importance of early ECMO initiation and contribute to the rapid advancement of this field.</p><p><b>Zegang Ruan</b>: Methodology; writing—original draft; investigation. <b>Yuhao Gan</b>: Methodology; writing—original draft; investigation. <b>Chenyang Xu</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":"531-532"},"PeriodicalIF":9.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491709","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
Neck triangle nerve enlargement in hereditary transthyretin amyloidosis correlates with changes in the autonomic, cardiac, and gastrointestinal systems 遗传性转甲状腺素淀粉样变性病的颈三角神经扩张与自主神经、心脏和胃肠道系统的变化相关。
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-10-22 DOI: 10.1111/joim.20019
Hsueh-Wen Hsueh, Chi-Chao Chao, Yen-Hung Lin, Ping-Huei Tseng, Mao-Yuan Su, Sung-Tsang Hsieh

Background

Hereditary transthyretin amyloidosis (ATTRv) is a hereditary disease that affects multiple bodily systems. Although sonography generally reveals enlargement of nerves in the limbs, the brachial plexus, and vagus nerve, the clinical significance of these findings remains unclear.

Methods

We performed sonographic measurements of the median nerve, cervical spinal nerves at the C5–C7 level, and the vagus nerve in patients with ATTRv and healthy controls. Clinical profiles and cardiac and gastrointestinal examination results were also collected for linear regression analysis.

Results

We recruited 47 patients with ATTRv (males/females: 34/13, age: 65.6 ± 5.3 years). The sampled segments were all significantly larger than those of the controls. In the clinical profiles, the sum of the Z scores of the neck triangle nerves (cervical spinal nerves and vagus nerve) and of all nerves (cervical spinal nerves, vagus nerve, and median nerve at the wrist) significantly correlated with the familial amyloid polyneuropathy stage, onset of autonomic nervous system (ANS) symptoms, and autonomic symptom scores. On cardiac examinations, several ultrasonography and magnetic resonance imaging parameters (primarily those that reflect heart volume) were found to be significantly correlated with the sum of the Z scores of the cervical spinal nerves but not with the Z score of the vagus nerve. In gastrointestinal evaluation, the cross-sectional area of the vagus nerve was correlated with gastric emptying time parameters on scintigraphy.

Conclusions

Neck triangle nerve enlargement on sonography correlated with parameters related to ANS dysfunction, indicating that nerve enlargement observed on ultrasonography may serve as a potential surrogate biomarker of ATTRv.

背景:遗传性转甲状腺素淀粉样变性(ATTRv)是一种影响多个身体系统的遗传性疾病。虽然声像图通常显示四肢神经、臂丛神经和迷走神经增大,但这些发现的临床意义仍不明确:我们对 ATTRv 患者和健康对照组的正中神经、C5-C7 颈椎神经和迷走神经进行了声像图测量。我们还收集了临床概况、心脏和胃肠道检查结果,用于线性回归分析:我们招募了 47 名 ATTRv 患者(男性/女性:34/13,年龄:65.6 ± 5.3 岁)。取样的节段均明显大于对照组。在临床资料中,颈部三角神经(颈脊神经和迷走神经)和所有神经(颈脊神经、迷走神经和腕部正中神经)的 Z 评分总和与家族性淀粉样变性多神经病分期、自律神经系统(ANS)症状发作和自律神经症状评分有明显相关性。在心脏检查中,发现一些超声波和磁共振成像参数(主要是那些反映心脏容积的参数)与颈脊神经的 Z 评分总和有明显相关性,但与迷走神经的 Z 评分无明显相关性。在胃肠道评估中,迷走神经的横截面积与闪烁扫描的胃排空时间参数相关:结论:超声检查中颈部三角神经的增大与自律神经系统功能障碍的相关参数有关,表明超声检查中观察到的神经增大可作为ATTRv的潜在替代生物标志物。
{"title":"Neck triangle nerve enlargement in hereditary transthyretin amyloidosis correlates with changes in the autonomic, cardiac, and gastrointestinal systems","authors":"Hsueh-Wen Hsueh,&nbsp;Chi-Chao Chao,&nbsp;Yen-Hung Lin,&nbsp;Ping-Huei Tseng,&nbsp;Mao-Yuan Su,&nbsp;Sung-Tsang Hsieh","doi":"10.1111/joim.20019","DOIUrl":"10.1111/joim.20019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary transthyretin amyloidosis (ATTRv) is a hereditary disease that affects multiple bodily systems. Although sonography generally reveals enlargement of nerves in the limbs, the brachial plexus, and vagus nerve, the clinical significance of these findings remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed sonographic measurements of the median nerve, cervical spinal nerves at the C5–C7 level, and the vagus nerve in patients with ATTRv and healthy controls. Clinical profiles and cardiac and gastrointestinal examination results were also collected for linear regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We recruited 47 patients with ATTRv (males/females: 34/13, age: 65.6 ± 5.3 years). The sampled segments were all significantly larger than those of the controls. In the clinical profiles, the sum of the <i>Z</i> scores of the neck triangle nerves (cervical spinal nerves and vagus nerve) and of all nerves (cervical spinal nerves, vagus nerve, and median nerve at the wrist) significantly correlated with the familial amyloid polyneuropathy stage, onset of autonomic nervous system (ANS) symptoms, and autonomic symptom scores. On cardiac examinations, several ultrasonography and magnetic resonance imaging parameters (primarily those that reflect heart volume) were found to be significantly correlated with the sum of the <i>Z</i> scores of the cervical spinal nerves but not with the <i>Z</i> score of the vagus nerve. In gastrointestinal evaluation, the cross-sectional area of the vagus nerve was correlated with gastric emptying time parameters on scintigraphy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Neck triangle nerve enlargement on sonography correlated with parameters related to ANS dysfunction, indicating that nerve enlargement observed on ultrasonography may serve as a potential surrogate biomarker of ATTRv.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 6","pages":"495-509"},"PeriodicalIF":9.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454306","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
Romosozumab versus denosumab in long-term users of glucocorticoids: A pilot randomized controlled trial 在长期使用糖皮质激素的患者中,Romosozumab 与 Denosumab 孰优孰劣?随机对照试验
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-10-10 DOI: 10.1111/joim.20017
Chi Chiu Mok, Kar Li Chan, Sau Mei Tse, Sammy Pak Lam Chen, Kathryn Choon Beng Tan, Wai Han Ma

Objective

To compare the efficacy of romosozumab (ROMO) and denosumab (DEN) in prevalent long-term glucocorticoid (GC) users.

Methods

Adult patients receiving oral prednisolone (≥5 mg/day) with high risk of fracture were randomized to receive subcutaneous ROMO (210 mg monthly) or DEN (60 mg 6-monthly) for 12 months, followed by DEN for two more doses. The primary end point was the change in spine bone mineral density (BMD) from Months 0 to 12. Secondary end points included changes in BMD of the spine/hip/femoral neck and bone turnover markers at various time points and adverse events.

Results

Seventy patients (age 62.6 ± 9.1 years; 96% women; median prednisolone dose 5.0 mg/day; duration of therapy 10.7 ± 7.4 years) were enrolled, and 63 completed the study. At Month 12, the spine BMD increased significantly in both ROMO (+7.3% ± 4.5%; p < 0.001) and DEN (+2.3% ± 3.1%; p < 0.001) groups. The absolute spine BMD gain from Months 0 to 12 was significantly greater in ROMO-treated patients (p < 0.001). Although the total hip BMD at Month 12 also increased significantly in the ROMO (+1.6% ± 3.3%; p = 0.01) and DEN groups (+1.6% ± 2.6%; p = 0.003), the absolute BMD gain was not significantly different between the groups. At Month 24, the spine BMD continued to increase in both the ROMO (+9.7% ± 4.8%; p < 0.001) and DEN group (+3.0% ± 3.0%; p < 0.001) compared to baseline, and the absolute BMD gain remained significantly greater in ROMO-treated patients. The total hip BMD continued to increase in both groups (ROMO +2.9% ± 3.7%; p < 0.001; DEN +2.2% ± 3.4%; p = 0.001), but the changes from baseline were similar. Injection site reaction was more frequently reported in ROMO-treated patients.

Conclusion

ROMO was superior to DEN in raising the spine BMD at Month 12 in chronic GC users. After switching to DEN, ROMO-treated patients continued to gain spine BMD to a greater extent than DEN until Month 24.

目的比较romosozumab(ROMO)和denosumab(DEN)对糖皮质激素(GC)长期使用者的疗效:方法:对口服泼尼松龙(≥5毫克/天)且有骨折高风险的成年患者进行随机分组,接受皮下注射ROMO(210毫克/月)或DEN(60毫克/6个月)治疗12个月,然后再接受两次DEN治疗。主要终点是脊柱骨质密度 (BMD) 从第 0 个月到第 12 个月的变化。次要终点包括不同时间点脊柱/髋部/股骨颈骨密度和骨转换标志物的变化以及不良事件:70名患者(年龄为62.6 ± 9.1岁;96%为女性;中位泼尼松龙剂量为5.0毫克/天;疗程为10.7 ± 7.4年)参加了研究,其中63人完成了研究。在第 12 个月,ROMO 和 DEN 的脊柱 BMD 均显著增加(+7.3% ± 4.5%;P 结论:ROMO 和 DEN 在提高脊柱 BMD 方面更优:在第 12 个月,ROMO 在提高慢性 GC 使用者的脊柱 BMD 方面优于 DEN。在改用 DEN 后,ROMO 治疗的患者直到第 24 个月的脊柱 BMD 增幅仍高于 DEN。
{"title":"Romosozumab versus denosumab in long-term users of glucocorticoids: A pilot randomized controlled trial","authors":"Chi Chiu Mok,&nbsp;Kar Li Chan,&nbsp;Sau Mei Tse,&nbsp;Sammy Pak Lam Chen,&nbsp;Kathryn Choon Beng Tan,&nbsp;Wai Han Ma","doi":"10.1111/joim.20017","DOIUrl":"10.1111/joim.20017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To compare the efficacy of romosozumab (ROMO) and denosumab (DEN) in prevalent long-term glucocorticoid (GC) users.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adult patients receiving oral prednisolone (≥5 mg/day) with high risk of fracture were randomized to receive subcutaneous ROMO (210 mg monthly) or DEN (60 mg 6-monthly) for 12 months, followed by DEN for two more doses. The primary end point was the change in spine bone mineral density (BMD) from Months 0 to 12. Secondary end points included changes in BMD of the spine/hip/femoral neck and bone turnover markers at various time points and adverse events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy patients (age 62.6 ± 9.1 years; 96% women; median prednisolone dose 5.0 mg/day; duration of therapy 10.7 ± 7.4 years) were enrolled, and 63 completed the study. At Month 12, the spine BMD increased significantly in both ROMO (+7.3% ± 4.5%; <i>p</i> &lt; 0.001) and DEN (+2.3% ± 3.1%; <i>p</i> &lt; 0.001) groups. The absolute spine BMD gain from Months 0 to 12 was significantly greater in ROMO-treated patients (<i>p</i> &lt; 0.001). Although the total hip BMD at Month 12 also increased significantly in the ROMO (+1.6% ± 3.3%; <i>p</i> = 0.01) and DEN groups (+1.6% ± 2.6%; <i>p</i> = 0.003), the absolute BMD gain was not significantly different between the groups. At Month 24, the spine BMD continued to increase in both the ROMO (+9.7% ± 4.8%; <i>p</i> &lt; 0.001) and DEN group (+3.0% ± 3.0%; <i>p</i> &lt; 0.001) compared to baseline, and the absolute BMD gain remained significantly greater in ROMO-treated patients. The total hip BMD continued to increase in both groups (ROMO +2.9% ± 3.7%; <i>p</i> &lt; 0.001; DEN +2.2% ± 3.4%; <i>p</i> = 0.001), but the changes from baseline were similar. Injection site reaction was more frequently reported in ROMO-treated patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ROMO was superior to DEN in raising the spine BMD at Month 12 in chronic GC users. After switching to DEN, ROMO-treated patients continued to gain spine BMD to a greater extent than DEN until Month 24.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 6","pages":"481-494"},"PeriodicalIF":9.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454307","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
Pyridoxal-5′-phosphate: A cost-effective treatment candidate for hypertensive patients? 5'-磷酸吡哆醛:高血压患者的经济有效治疗方法?
IF 9 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-10-10 DOI: 10.1111/joim.20015
Michaela Lellig, Mariano Rodríguez, Rodrigo López-Baltanás, Juliane Hermann, Julia Wollenhaupt, Heidi Noels, Walter Zidek, Martin Tepel, Felix Mahfoud, Joachim Jankowski, Juan R. Muñoz-Castañeda, Vera Jankowski

Objectives

Because angiotensin (Ang) II is an essential vasoconstrictive peptide, we analyzed the impact of its post-translational modification to pyruvamide–Ang II (Ang P) by pyridoxal-5′-phosphate (PLP) on blood pressure. PLP is a less expensive vitamin B6 derivative and, therefore, could be a cost-effective drug against hypertension.

Methods

Effect of Ang P on calcium ion entry into vascular smooth muscle cells (VSMCs) was analyzed. Binding affinity of Ang P to angiotensin II type 1 receptor (AT1R) was measured. Vasoconstrictive effect of Ang P was investigated using the bioassay of isolated perfused rat kidneys. Spontaneously hypertensive rats (SHR) were administered PLP. Additionally, Wistar Kyoto rats (WKY) received Ang II and PLP. Blood pressure was measured time-dependently.

Results

Ang II, incubated with PLP, was post-translationally modified to Ang P. Calcium ion entry in VSMCs was significantly lower with Ang P compared to Ang II. Binding affinity of Ang P to AT1R was lower compared to Ang II. Perfusion pressure of isolated perfused rat kidneys increased less by Ang P than by Ang II. Blood pressure of SHR treated with PLP decreased significantly. Blood pressure of WKY rats treated with Ang II was increased to hypertensive values, whereas blood pressure of WKY rats cotreated with Ang II and PLP was not.

Conclusion

PLP induces a post-translational modification of Ang II decreasing blood pressure in rats. Assuming that increased PLP intake in the form of vitamin B6 might reduce blood pressure in hypertensive patients, PLP might be a cost-effective drug against hypertension.

研究目的由于血管紧张素(Ang)II是一种重要的血管收缩肽,我们分析了5'-磷酸吡哆醛(PLP)将其翻译后修饰为丙酮酰胺-Ang II(Ang P)对血压的影响。PLP是一种价格较低的维生素B6衍生物,因此可以成为一种经济有效的高血压药物:方法:分析 Ang P 对钙离子进入血管平滑肌细胞(VSMCs)的影响。测量了 Ang P 与血管紧张素 II 1 型受体(AT1R)的结合亲和力。使用离体灌注大鼠肾脏的生物测定法研究了 Ang P 的血管收缩效应。给自发性高血压大鼠(SHR)注射 PLP。此外,Wistar Kyoto 大鼠(WKY)接受 Ang II 和 PLP。血压测量与时间有关:与 Ang II 相比,Ang P 在血管内皮细胞中的钙离子进入量明显降低。Ang P 与 AT1R 的结合亲和力低于 Ang II。Ang P 对离体灌注大鼠肾脏灌注压的增加低于 Ang II。用 PLP 治疗 SHR 的血压明显下降。用 Ang II 治疗的 WKY 大鼠的血压升高至高血压值,而 Ang II 和 PLP 联合治疗的 WKY 大鼠的血压则没有升高:结论:PLP 可诱导 Ang II 翻译后修饰,降低大鼠血压。假设增加维生素 B6 形式的 PLP 摄入量可降低高血压患者的血压,那么 PLP 可能是一种经济有效的高血压防治药物。
{"title":"Pyridoxal-5′-phosphate: A cost-effective treatment candidate for hypertensive patients?","authors":"Michaela Lellig,&nbsp;Mariano Rodríguez,&nbsp;Rodrigo López-Baltanás,&nbsp;Juliane Hermann,&nbsp;Julia Wollenhaupt,&nbsp;Heidi Noels,&nbsp;Walter Zidek,&nbsp;Martin Tepel,&nbsp;Felix Mahfoud,&nbsp;Joachim Jankowski,&nbsp;Juan R. Muñoz-Castañeda,&nbsp;Vera Jankowski","doi":"10.1111/joim.20015","DOIUrl":"10.1111/joim.20015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Because angiotensin (Ang) II is an essential vasoconstrictive peptide, we analyzed the impact of its post-translational modification to pyruvamide–Ang II (Ang P) by pyridoxal-5′-phosphate (PLP) on blood pressure. PLP is a less expensive vitamin B<sub>6</sub> derivative and, therefore, could be a cost-effective drug against hypertension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Effect of Ang P on calcium ion entry into vascular smooth muscle cells (VSMCs) was analyzed. Binding affinity of Ang P to angiotensin II type 1 receptor (AT<sub>1</sub>R) was measured. Vasoconstrictive effect of Ang P was investigated using the bioassay of isolated perfused rat kidneys. Spontaneously hypertensive rats (SHR) were administered PLP. Additionally, Wistar Kyoto rats (WKY) received Ang II and PLP. Blood pressure was measured time-dependently.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ang II, incubated with PLP, was post-translationally modified to Ang P. Calcium ion entry in VSMCs was significantly lower with Ang P compared to Ang II. Binding affinity of Ang P to AT<sub>1</sub>R was lower compared to Ang II. Perfusion pressure of isolated perfused rat kidneys increased less by Ang P than by Ang II. Blood pressure of SHR treated with PLP decreased significantly. Blood pressure of WKY rats treated with Ang II was increased to hypertensive values, whereas blood pressure of WKY rats cotreated with Ang II and PLP was not.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PLP induces a post-translational modification of Ang II decreasing blood pressure in rats. Assuming that increased PLP intake in the form of vitamin B<sub>6</sub> might reduce blood pressure in hypertensive patients, PLP might be a cost-effective drug against hypertension.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"296 5","pages":"435-448"},"PeriodicalIF":9.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386777","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
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Journal of Internal Medicine
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