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MicroRNA-30a inhibits cell proliferation in a sepsis-induced acute kidney injury model by targeting the YAP-TEAD complex MicroRNA-30a 通过靶向 YAP-TEAD 复合物抑制败血症诱导的急性肾损伤模型中的细胞增殖
Pub Date : 2024-04-01 DOI: 10.1016/j.jointm.2023.08.004
Junfeng Su , Ying Wang , Jing Xie , Long Chen , Xinxin Lin , Jiandong Lin , Xiongjian Xiao

Background

Acute kidney injury (AKI) is a primary feature of renal complications in patients with sepsis. MicroRNA (miRNA/miR)-30a is an essential regulator of cardiovascular diseases, tumors, phagocytosis, and other physical processes, but whether it participates in sepsis-induced AKI (sepsis-AKI) is unknown. We aimed to elucidate the functions and molecular mechanism underlying miR-30a activity in sepsis-AKI.

Methods

The classical cecal ligation and puncture (CLP) method and lipopolysaccharide (LPS)-induced Human Kidney 2 (HK-2) cells were used to establish in vivo and in vitro sepsis-AKI models. Specific pathogen-free and mature male Sprague-Dawley (SD) rats, aged 6–8 weeks (weight 200–250 g), were randomly divided into five-time phase subgroups. Fluid resuscitation with 30 mL/kg 37 °C saline was administered after the operation, without antibiotics. Formalin-fixed, paraffin-embedded kidney sections were stained with hematoxylin and eosin. SD rat kidney tissue samples were collected for analysis by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. HK-2 cells were transfected with hsa-miR-30a-3p mimics or inhibitors, and compared with untreated normal controls. RNA, protein, and cell viability were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot, and cell counting kit-8 methods. A Dual-Luciferase Assay Kit (Promega) was used to measure luciferase activity 48 h after transfection with miR-30a-3p mimics.

Results

Expression levels of miR-30a-3p and miR-30a-5p in renal tissues of the sepsis group were significantly reduced at 12 h and 24 h (P <0.05). Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were significantly increased in renal tissue 3 h after the operation in rats (P <0.05), and gradually decreased 6 h, 12 h, and 24 h after CLP. Levels of miR-30a-5p and miR-30a-3p were significantly down-regulated at 3 h after LPS treatment (P <0.05), and gradually decreased in HK-2 cells. One hour after LPS (10 µg/mL) treatment, TNF-α and IL-1β levels in HK-2 cells were significantly up-regulated (P < 0.05), and they were markedly down-regulated after 3 h (P <0.05). IL-6 expression levels began to rise after LPS treatment of cells, peaked at 6 h (P <0.05), and then decreased to the initial level within a few hours. Stimulation with 10 µg/mL LPS promoted HK-2 cells proliferation, which was inhibited after miR-30a-3p-mimic transfection. Bioinformatics prediction identified 37 potential miR-30a-3p target genes, including transcriptional enhanced associate domain 1 (TEAD1). After transfection of HK-2 cells with miR-30a-3p mimics and miR-30a-3p inhibitor, TEAD1 transcript was significantly up- and down-regulated, respectively (both P <0.05). After LPS treatment (24 h), expression

背景急性肾损伤(AKI)是脓毒症患者肾脏并发症的主要特征。微小RNA(miRNA/miR)-30a是心血管疾病、肿瘤、吞噬和其他物理过程的重要调节因子,但它是否参与脓毒症诱导的急性肾损伤(sepsis-AKI)尚不清楚。我们的目的是阐明 miR-30a 在脓毒症-AKI 中的功能和分子机制。方法采用经典的盲肠结扎和穿刺(CLP)方法和脂多糖(LPS)诱导的人肾 2(HK-2)细胞建立体内和体外脓毒症-AKI 模型。将年龄为 6-8 周(体重为 200-250 克)的特定无病原体成熟雄性 Sprague-Dawley (SD) 大鼠随机分为五个时相亚组。术后使用 30 mL/kg 37 °C 生理盐水进行液体复苏,不使用抗生素。对经福尔马林固定、石蜡包埋的肾脏切片进行苏木精和伊红染色。收集 SD 大鼠肾脏组织样本,通过实时定量聚合酶链反应和酶联免疫吸附试验进行分析。用 hsa-miR-30a-3p 模拟物或抑制剂转染 HK-2 细胞,并与未经处理的正常对照组进行比较。采用定量反转录聚合酶链反应(qRT-PCR)、Western 印迹和细胞计数试剂盒-8 方法评估 RNA、蛋白质和细胞活力。结果脓毒症组肾脏组织中 miR-30a-3p 和 miR-30a-5p 的表达水平在 12 h 和 24 h 时显著降低(P <0.05)。大鼠术后3 h肾组织中肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平明显升高(P <0.05),并在CLP术后6 h、12 h和24 h逐渐降低。LPS 处理后 3 小时,miR-30a-5p 和 miR-30a-3p 的水平明显下调(P <0.05),并在 HK-2 细胞中逐渐下降。LPS(10 µg/mL)处理一小时后,HK-2细胞中的TNF-α和IL-1β水平明显上调(P <0.05),3 h后明显下调(P <0.05)。细胞经 LPS 处理后,IL-6 表达水平开始上升,在 6 h 达到峰值(P <0.05),然后在几小时内降至初始水平。10 µg/mL LPS刺激可促进HK-2细胞增殖,而miR-30a-3p模拟物转染后可抑制增殖。生物信息学预测发现了 37 个潜在的 miR-30a-3p 靶基因,包括转录增强关联域 1(TEAD1)。用 miR-30a-3p 模拟物和 miR-30a-3p 抑制剂转染 HK-2 细胞后,TEAD1 转录本分别显著上调和下调(均为 P <0.05)。经 LPS 处理(24 h)后,抑制剂组 TEAD1 的表达明显增加(P <0.01),而模拟组则明显受到抑制(P <0.01)。在双荧光素酶报告实验中,miR-30a-3p 过表达会降低含 TEAD1-wt 质粒的荧光强度(P <0.01),但不影响含 TEAD1-muta 质粒的荧光强度。结论 在败血症-AKI 模型中,TNF-α、IL-1β 和 IL-6 等炎症因子的表达短暂增加,在此背景下,miR-30a 被下调。在 LPS 诱导的 HK-2 细胞中,下调的 miR-30a-3p 可能通过靶向 TEAD1 促进细胞增殖,这表明它有可能成为脓毒症-AKI 早期诊断的生物标志物。
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引用次数: 0
Effect of music therapy on short-term psychological and physiological outcomes in mechanically ventilated patients: A randomized clinical pilot study 音乐疗法对机械通气患者短期心理和生理结果的影响:随机临床试验研究
Pub Date : 2024-03-27 DOI: 10.1016/j.jointm.2024.01.006

Background

Elevated anxiety levels are common in patients on mechanical ventilation (MV) and may challenge recovery. Research suggests music-based interventions may reduce anxiety during MV. However, studies investigating specific music therapy techniques, addressing psychological and physiological well-being in patients on MV, are scarce.

Methods

This three-arm randomized clinical pilot study was conducted with MV patients admitted to the intensive care unit (ICU) of Hospital San José in Bogotá, Colombia between March 7, 2022, and July 11, 2022. Patients were divided into three groups: intervention group 1 (IG1), music-assisted relaxation; intervention group 2 (IG2), patient-preferred therapeutic music listening; and control group (CG), standard care. The main outcome measure was the 6-item State-Anxiety Inventory. Secondary outcomes were: pain (measured with a visual analog scale), resilience (measured with the Brief Resilience Scale), agitation/sedation (measured with the Richmond Agitation–Sedation Scale), vital signs (including heart rate, blood pressure, oxygen saturation, and respiratory rate), days of MV, extubation success, and days in the ICU. Additionally, three patients underwent electroencephalography during the interventions.

Results

Data from 23 patients were analyzed in this study. The age range of the patients was 24.0–84.0 years, with a median age of 66.0 years (interquartile range: 57.0–74.0). Of the 23 patients, 19 were female (82.6%). No statistically significant differences between the groups were observed for anxiety (P=0.330), pain (P=0.624), resilience (P=0.916), agitation/sedation (P=0.273), length of ICU stay (P=0.785), or vital signs. A statistically significant difference between the groups was found for days of MV (P=0.019). Electroencephalography measurements showed a trend toward delta and theta band power decrease for two patients and a power increase on both beta frequencies (slow and fast) in the frontal areas of the brain for one patient.

Conclusions

In this pilot study, music therapy did not significantly affect the anxiety levels in patients on MV. However, the interventions were widely accepted by the staff, patients, and caregivers and were safe, considering the critical medical status of the participants. Further large-scale randomized controlled trials are needed to investigate the potential benefits of music therapeutic interventions in this population.

Trial Registration ISRCTN trial registry identifier: ISRCTN16964680

背景机械通气(MV)患者的焦虑水平普遍升高,这可能会影响患者的康复。研究表明,基于音乐的干预措施可以减轻机械通气期间的焦虑。方法这项三臂随机临床试验研究于 2022 年 3 月 7 日至 2022 年 7 月 11 日期间在哥伦比亚波哥大圣何塞医院重症监护室(ICU)对接受机械通气的患者进行了研究。患者被分为三组:干预组1(IG1),音乐辅助放松;干预组2(IG2),患者偏好的治疗性音乐聆听;对照组(CG),标准护理。主要结果测量为 6 项国家焦虑量表。次要结果包括:疼痛(用视觉模拟量表测量)、恢复力(用简易恢复力量表测量)、躁动/镇静(用里士满躁动-镇静量表测量)、生命体征(包括心率、血压、血氧饱和度和呼吸频率)、MV 天数、拔管成功率和在重症监护室的天数。此外,3 名患者在干预期间接受了脑电图检查。患者的年龄范围为 24.0-84.0 岁,中位年龄为 66.0 岁(四分位距:57.0-74.0)。23 名患者中有 19 名女性(82.6%)。两组患者在焦虑(P=0.330)、疼痛(P=0.624)、恢复力(P=0.916)、躁动/镇静(P=0.273)、重症监护室住院时间(P=0.785)或生命体征方面无明显统计学差异。两组之间在 MV 天数方面存在统计学差异(P=0.019)。脑电图测量结果显示,两名患者的 delta 和 theta 波段功率呈下降趋势,一名患者大脑额叶区域的两个 beta 频率(慢速和快速)的功率均呈上升趋势。然而,考虑到参与者的危重医疗状况,干预措施得到了工作人员、患者和护理人员的广泛接受,并且是安全的。需要进一步开展大规模的随机对照试验,以研究音乐治疗干预对这一人群的潜在益处:ISRCTN16964680
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引用次数: 0
Bloodstream infections in the era of the COVID-19 pandemic: Changing epidemiology of antimicrobial resistance in the intensive care unit 2019 年冠状病毒大流行时代的血流感染:重症监护病房抗菌药耐药性流行病学的变化
Pub Date : 2024-03-27 DOI: 10.1016/j.jointm.2023.12.004
Fotinie Ntziora, Efthymia Giannitsioti

The Coronavirus disease 2019 (COVID-19) pandemic increased the burden of critically ill patients who required hospitalization in the intensive care unit (ICU). Bacterial and fungal co-infections, including bloodstream infections (BSIs), increased significantly in ICU patients with COVID-19; this had a significant negative impact on patient outcomes. Reported data pertaining to BSI episodes from the ICU setting during the COVID-19 pandemic were collected and analyzed for this narrative review. We searched the PubMed database for articles published between March 2020 and October 2023; the terms “COVID-19” AND “bloodstream infections” AND “ICU” were used for the search. A total of 778 articles were retrieved; however, only 27 were exclusively related to BSIs in ICU patients with COVID-19. Data pertaining to the epidemiological characteristics, risk factors, characteristics of bacterial and fungal BSIs, patterns of antimicrobial resistance, and comparisons between ICU and non-ICU patients during and before the COVID-19 pandemic were obtained. Data on antimicrobial stewardship and infection-control policies were also included. The rates of BSI were found to have increased among ICU patients with COVID-19 than in non-COVID-19 patients and those admitted during the pre-pandemic period. Male gender, 60–70 years of age, increased body mass index, high Sequential Organ Failure Assessment scores at admission, prolonged hospital and ICU stay, use of central lines, invasive ventilation, and receipt of extracorporeal membrane oxygenation were all defined as risk factors for BSI. The use of immune modulators for COVID-19 appeared to increase the risk of BSI; however, the available data are conflicting. Overall, Enterococci, Acinetobacter baumannii, and Candida spp. emerged as prominent infecting organisms during the pandemic; along with Enterobacterales and Pseudomonas aeruginosa they had a significant impact on mortality. Multidrug-resistant organisms prevailed in the ICU, especially if antimicrobial resistance was established before the COVID-19 pandemic and were significantly associated with increased mortality rates. The unnecessary and widespread use of antibiotics further increased the prevalence of multidrug-resistant organisms during COVID-19. Notably, the data indicated a significant increase in contaminants in blood cultures; this highlighted the decline in compliance with infection-control measures, especially during the initial waves of the pandemic. The implementation of infection-control policies along with antibiotic stewardship succeeded in significantly reducing the rates of blood contamination and BSI pathogens. BSIs considerably worsened outcomes in patients with COVID-19 who were admitted to ICUs. Further studies are needed to evaluate adequate preventive and control measures that may increase preparedness for the future.

2019年冠状病毒病(COVID-19)大流行加重了需要在重症监护室(ICU)住院治疗的重症患者的负担。在感染 COVID-19 的重症监护病房患者中,细菌和真菌合并感染(包括血流感染 (BSI))显著增加;这对患者的预后产生了重大负面影响。本综述收集并分析了 COVID-19 大流行期间 ICU 中 BSI 病例的相关报告数据。我们在 PubMed 数据库中检索了 2020 年 3 月至 2023 年 10 月间发表的文章;检索词为 "COVID-19"、"血流感染 "和 "ICU"。共检索到 778 篇文章;但是,只有 27 篇文章完全与患有 COVID-19 的 ICU 患者的 BSI 相关。研究获得了有关流行病学特征、风险因素、细菌和真菌 BSIs 特征、抗菌素耐药性模式以及 COVID-19 大流行期间和之前 ICU 和非 ICU 患者之间的比较等方面的数据。此外还包括抗菌药物管理和感染控制政策方面的数据。研究发现,与非 COVID-19 患者和大流行前的患者相比,COVID-19 在 ICU 患者中的 BSI 感染率有所上升。男性、60-70 岁、体重指数增高、入院时器官功能衰竭序列评估评分高、住院时间和重症监护室停留时间长、使用中心管路、侵入性通气和接受体外膜氧合都被定义为 BSI 的风险因素。使用免疫调节剂治疗 COVID-19 似乎会增加 BSI 的风险,但现有数据并不一致。总体而言,肠球菌、鲍曼不动杆菌和念珠菌属是大流行期间的主要感染病菌;它们与肠杆菌和铜绿假单胞菌一起对死亡率产生了重大影响。多重耐药菌在重症监护病房中普遍存在,尤其是在 COVID-19 大流行之前就已产生抗菌素耐药性的情况下,这些耐药菌与死亡率的增加有很大关系。在 COVID-19 期间,不必要地广泛使用抗生素进一步增加了耐多药生物的流行。值得注意的是,数据显示血液培养物中的污染物显著增加;这凸显了感染控制措施合规性的下降,尤其是在大流行的最初几波。感染控制政策的实施以及抗生素管理成功地大幅降低了血液污染和 BSI 病原体的发生率。对于入住重症监护病房的 COVID-19 患者来说,BSI 会大大恶化他们的预后。需要进一步研究评估适当的预防和控制措施,以便为未来做好准备。
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引用次数: 0
The causal role of immune cells in susceptibility and severity of COVID-19: A bidirectional Mendelian randomization study 免疫细胞在 COVID-19 易感性和严重程度中的因果作用:双向孟德尔随机研究
Pub Date : 2024-03-21 DOI: 10.1016/j.jointm.2024.02.001
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引用次数: 0
Outcomes of intracranial hemorrhage in critically ill patients with acute leukemia: Results of a retrospective cohort study 急性白血病重症患者颅内出血的预后:回顾性队列研究结果
Pub Date : 2024-03-20 DOI: 10.1016/j.jointm.2023.12.008

Background

Admission to the intensive care unit (ICU) is frequently required for patients with acute leukemia (AL) because of life-threatening complications such as intracranial hemorrhage (IH). In this study, we evaluated the impact of IH on survival and neurological outcomes in this population.

Methods

This was a single-center retrospective cohort study including adult patients with AL requiring ICU admission and experiencing IH between 2002 and 2019 at Saint Louis Hospital. Leukemia type was determined according to the French–American–British classification. Brain imaging (either computed tomography or magnetic resonance imaging) was available for all the patients. The primary endpoint of the study was to describe the clinical and biological characteristics and evaluate the mortality and neurological outcome of patients hospitalized in the ICU with newly diagnosed AL and IH. The secondary endpoint was to identify predictive factors of IH in these patients.

Results

Thirty-five patients with AL were included, median age of the patients was 59.00 (interquartile range [IQR]: 36.00–66.00) years. Twenty-nine patients (82.9%) had acute myeloid leukemia, including 12 patients with acute promyelocytic leukemia. Thrombocytopenia was constant, and 48.5% of patients had disseminated intravascular coagulation (DIC). At ICU admission, the median Sequential Organ Failure Assessment score was 5 (IQR: 3–9). The median time between AL onset and IH was 2.0 (IQR: 0.0–9.5) days. The ICU and hospital mortality rates were 60.0% (n =21) and 65.7% (n=23), respectively. In univariate analysis, mechanical ventilation and stupor were associated with mortality, but DIC and acute promyelocytic leukemia were not. Upon multivariate analysis, stupor or coma was the only factor significantly associated with a poor outcome (odds ratio = 8.56, 95 % confidence interval: 2.40 to 30.46).

Conclusion

IH is associated with a high mortality rate in AL patients, with stupor or coma at the onset of intracranial bleeding being independently associated with poor outcomes.

背景急性白血病(AL)患者由于颅内出血(IH)等危及生命的并发症而经常需要入住重症监护病房(ICU)。方法这是一项单中心回顾性队列研究,研究对象包括2002年至2019年期间圣路易斯医院需要入住重症监护室并发生颅内出血的成人急性白血病患者。白血病类型根据法-美-英分类法确定。所有患者均可进行脑成像(计算机断层扫描或磁共振成像)。研究的主要终点是描述新诊断为AL和IH的重症监护病房住院患者的临床和生物学特征,并评估其死亡率和神经系统预后。结果35名AL患者被纳入研究,患者的中位年龄为59.00(四分位间距[IQR]:36.00-66.00)岁。29 名患者(82.9%)患有急性髓细胞白血病,其中包括 12 名急性早幼粒细胞白血病患者。血小板持续减少,48.5%的患者出现弥散性血管内凝血(DIC)。入住重症监护室时,器官功能衰竭顺序评估的中位数为 5 分(IQR:3-9)。AL发病与IH之间的中位时间为2.0天(IQR:0.0-9.5)。重症监护室和医院死亡率分别为 60.0%(21 人)和 65.7%(23 人)。在单变量分析中,机械通气和昏迷与死亡率有关,但 DIC 和急性早幼粒细胞白血病与死亡率无关。在多变量分析中,昏迷或昏迷是唯一与不良预后显著相关的因素(几率比 = 8.56,95 % 置信区间:2.40 至 30.46)。
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引用次数: 0
Hygrometry behavior during high-flow nasal oxygen therapy and non-invasive mechanical ventilation: A narrative review of bench to clinical studies 高流量鼻氧治疗和无创机械通气期间的血氧饱和度行为:从台架到临床研究的叙述性综述
Pub Date : 2024-03-19 DOI: 10.1016/j.jointm.2024.01.004

Recently, there has been growing interest in knowing the best hygrometry level during high-flow nasal oxygen and non-invasive ventilation (NIV) and its potential influence on the outcome. Various studies have shown that breathing cold and dry air results in excessive water loss by nasal mucosa, reduced mucociliary clearance, increased airway resistance, reduced epithelial cell function, increased inflammation, sloughing of tracheal epithelium, and submucosal inflammation. With the Coronavirus Disease 2019 pandemic, using high-flow nasal oxygen with a heated humidifier has become an emerging form of non-invasive support among clinicians. However, we cannot always assume stable humidification. Similarly, there are no clear guidelines for using humidification during NIV, although humidification of inspired gas during invasive ventilation is an accepted standard of care. NIV disturbs the normal physiological system that warms and humidifies inspired gases. If NIV is supplied through an intensive care unit ventilator that utilizes anhydrous gases from compressed wall air and oxygen, the risk of dryness increases. In addition, patients with acute respiratory failure tend to breathe through the mouth during NIV, which is a less efficient route than nasal breathing for adding heat and moisture to the inspired gas. Obstructive sleep apnea syndrome is one of the most important indications for chronic use of NIV at home. Available data suggest that up to 60% of patients with obstructive sleep apnea syndrome who use continuous positive airway pressure therapy experience nasal congestion and dryness of the mouth and nose. Therefore, humidifying the inspired gas in NIV may be essential for patient comfort and compliance with treatment. We aimed to review the available bench and clinical studies that addressed the utility of hygrometry in NIV and nasal high-flow oxygen and discuss the technical limitations of different humidification systems for both systems.

最近,人们对了解高流量鼻氧和无创通气(NIV)期间的最佳湿度水平及其对治疗效果的潜在影响越来越感兴趣。多项研究表明,呼吸寒冷干燥的空气会导致鼻黏膜失水过多、黏膜纤毛清除率降低、气道阻力增加、上皮细胞功能降低、炎症加重、气管上皮脱落和黏膜下炎症。随着 2019 年冠状病毒病的大流行,使用带有加热加湿器的高流量鼻氧已成为临床医生中一种新兴的无创支持方式。然而,我们不能总是假设加湿效果稳定。同样,尽管在有创通气期间对吸入气体进行加湿是公认的护理标准,但在 NIV 期间使用加湿也没有明确的指导原则。NIV 会干扰对吸入气体进行加温和加湿的正常生理系统。如果通过使用压缩壁空气和氧气中的无水气体的重症监护病房呼吸机提供 NIV,干燥的风险就会增加。此外,急性呼吸衰竭患者在进行 NIV 时倾向于用嘴呼吸,这种方式在为吸入气体增加热量和湿度方面不如鼻腔呼吸有效。阻塞性睡眠呼吸暂停综合症是在家中长期使用 NIV 的最重要适应症之一。现有数据表明,多达 60% 的阻塞性睡眠呼吸暂停综合症患者在使用持续气道正压疗法时会出现鼻塞和口鼻干燥的症状。因此,对 NIV 吸入气体进行加湿可能对患者的舒适度和治疗依从性至关重要。我们旨在回顾现有的有关湿度计在 NIV 和鼻腔高流量供氧中的实用性的工作台和临床研究,并讨论这两种系统中不同加湿系统的技术局限性。
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引用次数: 0
Fungal infections in immunocompromised critically ill patients 免疫力低下的重症患者的真菌感染
Pub Date : 2024-03-16 DOI: 10.1016/j.jointm.2024.01.005
José Garnacho-Montero, Irene Barrero-García, Cristina León-Moya

Diverse pathogenic fungi can produce severe infections in immunocompromised patients, thereby justifying intensive care unit (ICU) admissions. In some cases, the infections can develop in immunocompromised patients who were previously admitted to the ICU. Aspergillus spp., Pneumocystis jirovecii, Candida spp., and Mucorales are the fungi that are most frequently involved in these infections. Diagnosis continues to be challenging because symptoms and signs are unspecific. Herein, we provide an in-depth review about the diagnosis, with emphasis on recent advances, and treatment of these invasive fungal infections in the ICU setting.

多种致病真菌会对免疫力低下的患者造成严重感染,因此需要入住重症监护病房(ICU)。在某些情况下,感染可能发生在曾入住过重症监护室的免疫力低下患者身上。曲霉菌属、肺孢子菌属、念珠菌属和粘菌属是这些感染中最常见的真菌。由于症状和体征不具有特异性,因此诊断仍然具有挑战性。在此,我们将深入探讨 ICU 环境中这些侵袭性真菌感染的诊断、最新进展和治疗方法。
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引用次数: 0
When to start renal replacement therapy in acute kidney injury: What are we waiting for? 急性肾损伤患者何时开始肾替代治疗?我们还在等什么?
Pub Date : 2024-03-07 DOI: 10.1016/j.jointm.2023.12.005
Lixia Liu, Zhenjie Hu

Acute kidney injury remains a serious condition with a high mortality risk. In the absence of any new drugs, renal replacement therapy (RRT) is the most important treatment option. Randomized controlled trials have concluded that in critically ill patients without an emergency indication for RRT, a watchful waiting strategy is safe; however, further delays in RRT did not seem to confer any benefit, rather was associated with potential harm. During this process, balancing the risks of complications due to an unnecessary intervention with the risk of not correcting a potentially life-threatening complication remains a challenge. Dynamic renal function assessment, especially dynamic assessment of renal demand-capacity matching, combined with renal biomarkers such as neutrophil gelatinase-associated lipocalin and furosemide stress test, is helpful to identify which patients and when the patients may benefit from RRT.

急性肾损伤仍然是一种严重的疾病,死亡率很高。在没有任何新药的情况下,肾脏替代疗法(RRT)是最重要的治疗选择。随机对照试验得出的结论是,对于没有 RRT 紧急指征的重症患者,采取观察等待策略是安全的;但是,进一步延迟 RRT 似乎并不会带来任何益处,反而会带来潜在的危害。在这一过程中,如何在不必要的干预导致并发症的风险与无法纠正可能危及生命的并发症的风险之间取得平衡仍然是一项挑战。动态肾功能评估,尤其是肾脏需求-容量匹配的动态评估,结合肾脏生物标志物,如中性粒细胞明胶酶相关脂质钙蛋白和呋塞米应激试验,有助于确定哪些患者以及患者何时可能从 RRT 中获益。
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引用次数: 0
The 6-hour lactate clearance rate in predicting 30-day mortality in cardiogenic shock 预测心源性休克患者 30 天死亡率的 6 小时乳酸清除率
Pub Date : 2024-03-02 DOI: 10.1016/j.jointm.2024.01.003
Junfeng Wang, Mingxia Ji

Background

Early evaluation of prognosis in cardiogenic shock (CS) is crucial for tailored treatment selection. Both lactate clearance and lactate levels are considered useful prognostic biomarkers in patients with CS. However, there is yet no literature comparing the 6-hour lactate clearance rate (Δ6Lac) with lactate levels measured at admission (L1) and after 6 h (L2) to predict 30-day mortality in CS.

Methods

In this observational cohort study, 95 patients with CS were treated at Department of Intensive Care Unit, Yiwu Central Hospital between January 2020 and December 2022. Of these, 88 patients met the eligibility criteria. The lactate levels were measured after admission (L1) as the baseline lactate value, and were measured after 6 h (L2) following admission. The primary endpoint of the study was survival rate at 30 days. A receiver operating characteristic curve was used for data analysis. Univariate and multivariate Cox regression analyses were performed based on Δ6Lac. Kaplan–Meier (KM) survival curves were generated to compare the 30-day survival rates among L1, L2, and Δ6Lac.

Results

The Δ6Lac model showed the highest area under the curve value (0.839), followed by the L2 (0.805) and L1 (0.668) models. The Δ6Lac model showed a sensitivity of 84.2% and specificity of 75.4%. The L1 and L2 models had sensitivities of 57.9% each and specificities of 89.9% and 98.6%, respectively. The cut-off values for Δ6Lac, L1, and L2 were 18.2%, 6.7 mmol/L, and 6.1 mmol/L, respectively. Univariate Cox regression analysis revealed a significant association between Δ6Lac and 30-day mortality. After adjusting for five models in multivariate Cox regression, Δ6Lac remained a significant risk factor for 30-day mortality in patients with CS. In our fifth multivariate Cox regression model, Δ6Lac remained a risk factor associated with 30-day mortality (hazard ratio [HR]=5.14, 95% confidence interval [CI]: 1.48 to 17.89, P=0.010) as well as L2 (HR=8.42, 95% CI: 1.26 to 56.22, P=0.028). The KM survival curve analysis revealed that L1 >6.7 mmol/L (HR=8.08, 95% CI: 3.23 to 20.20, P <0.001), L2 >6.1 mmol/L (HR=25.97, 95% CI: 9.76 to 69.15, P <0.001), and Δ6Lac ≤18.2% (HR=8.92, 95% CI: 2.95 to 26.95, P <0.001) were associated with a higher risk of 30-day mortality.

Conclusions

Δ6Lac is a better predictor for 30-day mortality in CS than lactate levels at admission. It has a predictive value equivalent to that of lactate level at 6 h after admission, making it an important surrogate indicator for evaluating the suitability as well as poor prognosis after CS treatment. We found that a cut-off value of 18.2% for Δ6Lac provided the most accurate assessment of early prognosis in CS.

背景早期评估心源性休克(CS)的预后对于选择有针对性的治疗至关重要。乳酸清除率和乳酸水平都被认为是预测心源性休克患者预后的有用生物标志物。然而,目前还没有文献将6小时乳酸清除率(Δ6Lac)与入院时(L1)和6小时后(L2)测量的乳酸水平进行比较,以预测CS患者30天的死亡率。方法在这项观察性队列研究中,义乌市中心医院重症医学科在2020年1月至2022年12月期间收治了95例CS患者。其中,88 名患者符合资格标准。入院后测量的乳酸水平(L1)为基线乳酸值,入院后 6 小时后测量的乳酸水平(L2)为基线乳酸值。研究的主要终点是 30 天的存活率。数据分析采用接收器操作特征曲线。根据Δ6Lac进行了单变量和多变量Cox回归分析。结果 Δ6Lac模型的曲线下面积值最高(0.839),其次是L2模型(0.805)和L1模型(0.668)。Δ6Lac模型的灵敏度为84.2%,特异性为75.4%。L1 和 L2 模型的灵敏度分别为 57.9%,特异性分别为 89.9% 和 98.6%。Δ6Lac、L1 和 L2 的临界值分别为 18.2%、6.7 mmol/L 和 6.1 mmol/L。单变量 Cox 回归分析显示,Δ6Lac 与 30 天死亡率之间存在显著关联。在多变量 Cox 回归中对五个模型进行调整后,Δ6Lac 仍是 CS 患者 30 天死亡率的重要风险因素。在我们的第五个多变量 Cox 回归模型中,Δ6Lac 仍然是与 30 天死亡率相关的风险因素(危险比 [HR]=5.14, 95% 置信区间 [CI]:1.48至17.89,P=0.010)以及L2(HR=8.42,95% CI:1.26至56.22,P=0.028)。KM 生存曲线分析显示,L1 >6.7 mmol/L (HR=8.08, 95% CI: 3.23 to 20.20, P <0.001)、L2 >6.1 mmol/L (HR=25.97, 95% CI: 9.76 to 69.15, P <0.001)、Δ6Lac ≤18.2%(HR=8.结论与入院时的乳酸水平相比,Δ6Lac能更好地预测CS患者30天内的死亡率。结论Δ6Lac比入院时的乳酸水平更能预测CS患者的30天死亡率,其预测价值与入院后6小时的乳酸水平相当,因此它是评估CS治疗是否合适以及预后是否不良的重要替代指标。我们发现,Δ6Lac 的临界值为 18.2%,能最准确地评估 CS 的早期预后。
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引用次数: 0
Understanding antimicrobial pharmacokinetics in critically ill patients to optimize antimicrobial therapy: A narrative review 了解重症患者的抗菌药物代谢动力学,优化抗菌治疗:叙述性综述
Pub Date : 2024-02-29 DOI: 10.1016/j.jointm.2023.12.007
Claire Roger

Effective treatment of sepsis not only demands prompt administration of appropriate antimicrobials but also requires precise dosing to enhance the likelihood of patient survival. Adequate dosing refers to the administration of doses that yield therapeutic drug concentrations at the infection site. This ensures a favorable clinical and microbiological response while avoiding antibiotic-related toxicity. Therapeutic drug monitoring (TDM) is the recommended approach for attaining these goals. However, TDM is not universally available in all intensive care units (ICUs) and for all antimicrobial agents. In the absence of TDM, healthcare practitioners need to rely on several factors to make informed dosing decisions. These include the patient's clinical condition, causative pathogen, impact of organ dysfunction (requiring extracorporeal therapies), and physicochemical properties of the antimicrobials. In this context, the pharmacokinetics of antimicrobials vary considerably between different critically ill patients and within the same patient over the course of ICU stay. This variability underscores the need for individualized dosing. This review aimed to describe the main pathophysiological changes observed in critically ill patients and their impact on antimicrobial drug dosing decisions. It also aimed to provide essential practical recommendations that may aid clinicians in optimizing antimicrobial therapy among critically ill patients.

有效治疗败血症不仅需要及时使用适当的抗菌药物,还需要精确给药以提高患者存活的可能性。足量给药是指给药剂量能在感染部位产生治疗药物浓度。这既能确保良好的临床和微生物反应,又能避免与抗生素相关的毒性。治疗药物监测(TDM)是实现这些目标的推荐方法。然而,并非所有重症监护病房(ICU)和所有抗菌药物都能进行治疗药物监测。在没有 TDM 的情况下,医护人员需要依靠多种因素来做出明智的用药决定。这些因素包括患者的临床状况、致病病原体、器官功能障碍(需要体外疗法)的影响以及抗菌药物的理化特性。在这种情况下,不同危重病人之间以及同一病人在重症监护室住院期间的抗菌药物药代动力学差异很大。这种差异凸显了个体化用药的必要性。本综述旨在描述在重症患者身上观察到的主要病理生理变化及其对抗菌药物剂量决定的影响。它还旨在提供基本的实用建议,以帮助临床医生优化重症患者的抗菌治疗。
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引用次数: 0
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Journal of intensive medicine
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