Pub Date : 2025-01-01DOI: 10.1016/j.jointm.2024.07.007
Jingjing Wang , Changxing Chen , Zhanqi Zhao , Puyu Deng , Chenchen Zhang , Yu Zhang , Hui Lv , Daonan Chen , Hui Xie , Ruilan Wang
<div><h3>Background</h3><div>Awake prone positioning (APP) can reportedly reduce the need for intubation and help improve prognosis of patients with acute hypoxemic respiratory failure (AHRF) infected with COVID-19. However, its physiological mechanism remains unclear. In this study, we evaluated the effect of APP on lung ventilation in patients with moderate-to-severe AHRF to better understand the effects on ventilation distribution and to prevent intubation in non-intubated patients.</div></div><div><h3>Methods</h3><div>The prospective study was performed in the Department of Critical Care Medicine at Shanghai General Hospital, China, from January 2021 to November 2022. The study included patients with AHRF (partial pressure of oxygen [PaO<sub>2</sub>]/inspired oxygen concentration [FiO<sub>2</sub>] <200 mmHg or oxygen saturation [SpO<sub>2</sub>]/FiO<sub>2</sub> <235) treated with high-flow nasal oxygen. Electrical impedance tomography (EIT) measurements including center of ventilation (COV), global inhomogeneity (GI) index, and regional ventilation delay (RVD) index were performed in the supine position (T<sub>0</sub>), 30 min after the start of APP (T<sub>1</sub>), and 30 min returning to supine position after the APP (T<sub>2</sub>). Clinical parameters like SpO<sub>2</sub>, respiratory rate (RR), FiO<sub>2</sub>, heart rate (HR), and ROX (the ratio of SpO<sub>2</sub> as measured by pulse oximetry/FiO<sub>2</sub> to RR) were also recorded simultaneously at T<sub>0</sub>, T<sub>1</sub>, and T<sub>2</sub>. To evaluate the effect of the time points on the variables, Mauchly's test was performed for sphericity and repeated measures analysis of variance was applied with Bonferroni's <em>post hoc</em> multiple comparisons.</div></div><div><h3>Results</h3><div>Ten patients were enrolled. The PaO<sub>2</sub>/FiO<sub>2</sub> ratio was (111.4±33.4) mmHg at the time of recruitment. ROX showed a significant increase after initiation of APP {median (interquartile range [IQR]): T<sub>0</sub>: 7.5 (6.0–10.1) <em>vs.</em> T<sub>1</sub>: 7.6 (6.4–9.3) <em>vs.</em> T<sub>2</sub>: 8.3 (7.2–11.0), <em>P</em>=0.043}. RR (<em>P</em>=0.409), HR (<em>P</em>=0.417), and SpO<sub>2</sub>/FiO<sub>2</sub> (<em>P</em>=0.262) did not change significantly during prone positioning (PP). The COV moved from the ventral area to the dorsal area (T<sub>0</sub>: 48.8%±6.2% <em>vs.</em> T<sub>1</sub>: 54.8%±6.8% <em>vs.</em> T<sub>2</sub>: 50.3%±6.1%, <em>P</em>=0.030) after APP. The GI decreased significantly after APP (T<sub>0</sub>: median=42.7 %, [IQR: 38.3%–47.5%] <em>vs.</em> T<sub>1</sub>: median=38.2%, [IQR: 34.6%–50.7%] <em>vs.</em> T<sub>2</sub>: median=37.4%, [IQR: 34.2%–41.4%], <em>P</em>=0.049). RVD (<em>P</em>=0.794) did not change after APP.</div></div><div><h3>Conclusions</h3><div>APP can improve ventilation distribution and homogeneity of lung ventilation as assessed by EIT in non-intubated patients with AHRF.</div><div><strong>Trail Registration</strong> C
背景：据报道，清醒俯卧位（APP）可以减少COVID-19感染的急性低氧性呼吸衰竭（AHRF）患者的插管需求，并有助于改善预后。然而，其生理机制尚不清楚。在本研究中，我们评估APP对中重度AHRF患者肺通气的影响，以更好地了解其对通气分布的影响，并预防非插管患者插管。方法：前瞻性研究于2021年1月至2022年11月在中国上海总医院重症医学科进行。研究纳入AHRF患者（氧分压[PaO2]/吸入氧浓度[FiO2] 2]/FiO2 0）， APP开始后30分钟（T1）， APP结束后30分钟恢复仰卧位（T2）。同时记录T0、T1、T2时SpO2、呼吸速率（RR）、FiO2、心率（HR）、ROX（脉搏血氧仪测得SpO2 /FiO2与RR之比）等临床参数。为了评估时间点对变量的影响，采用Mauchly检验进行球度检验，并采用Bonferroni事后多重比较进行重复测量方差分析。结果：10例患者入组。招募时PaO2/FiO2比值为（111.4±33.4）mmHg。APP启动后ROX显著升高{中位数（四分位数间距[IQR]）： T0: 7.5 (6.0-10.1) vs. T1: 7.6 (6.4-9.3) vs. T2: 8.3 (7.2-11.0)， P=0.043}。俯卧位（PP）时，RR （P=0.409）、HR （P=0.417）和SpO2/FiO2 （P=0.262）无显著变化。APP术后冠状病毒由腹侧区向背侧区转移（T0: 48.8%±6.2% vs T1: 54.8%±6.8% vs T2: 50.3%±6.1%，P=0.030）。APP术后GI明显下降（T0：中位数= 42.7%,[IQR: 38.3% ~ 47.5%] vs T1：中位数=38.2%,[IQR: 34.6% ~ 50.7%] vs T2：中位数=37.4%,[IQR: 34.2% ~ 41.4%]， P=0.049）。应用APP后RVD无显著变化（P=0.794）。结论：应用APP可改善非插管AHRF患者通气分布和肺通气均匀性。中国临床试验注册号：ChiCTR2000035895。
{"title":"Awake prone positioning and ventilation distribution as assessed by electric impedance tomography in patients with non-COVID-19 acute hypoxemic respiratory failure: A prospective physiology study","authors":"Jingjing Wang , Changxing Chen , Zhanqi Zhao , Puyu Deng , Chenchen Zhang , Yu Zhang , Hui Lv , Daonan Chen , Hui Xie , Ruilan Wang","doi":"10.1016/j.jointm.2024.07.007","DOIUrl":"10.1016/j.jointm.2024.07.007","url":null,"abstract":"<div><h3>Background</h3><div>Awake prone positioning (APP) can reportedly reduce the need for intubation and help improve prognosis of patients with acute hypoxemic respiratory failure (AHRF) infected with COVID-19. However, its physiological mechanism remains unclear. In this study, we evaluated the effect of APP on lung ventilation in patients with moderate-to-severe AHRF to better understand the effects on ventilation distribution and to prevent intubation in non-intubated patients.</div></div><div><h3>Methods</h3><div>The prospective study was performed in the Department of Critical Care Medicine at Shanghai General Hospital, China, from January 2021 to November 2022. The study included patients with AHRF (partial pressure of oxygen [PaO<sub>2</sub>]/inspired oxygen concentration [FiO<sub>2</sub>] <200 mmHg or oxygen saturation [SpO<sub>2</sub>]/FiO<sub>2</sub> <235) treated with high-flow nasal oxygen. Electrical impedance tomography (EIT) measurements including center of ventilation (COV), global inhomogeneity (GI) index, and regional ventilation delay (RVD) index were performed in the supine position (T<sub>0</sub>), 30 min after the start of APP (T<sub>1</sub>), and 30 min returning to supine position after the APP (T<sub>2</sub>). Clinical parameters like SpO<sub>2</sub>, respiratory rate (RR), FiO<sub>2</sub>, heart rate (HR), and ROX (the ratio of SpO<sub>2</sub> as measured by pulse oximetry/FiO<sub>2</sub> to RR) were also recorded simultaneously at T<sub>0</sub>, T<sub>1</sub>, and T<sub>2</sub>. To evaluate the effect of the time points on the variables, Mauchly's test was performed for sphericity and repeated measures analysis of variance was applied with Bonferroni's <em>post hoc</em> multiple comparisons.</div></div><div><h3>Results</h3><div>Ten patients were enrolled. The PaO<sub>2</sub>/FiO<sub>2</sub> ratio was (111.4±33.4) mmHg at the time of recruitment. ROX showed a significant increase after initiation of APP {median (interquartile range [IQR]): T<sub>0</sub>: 7.5 (6.0–10.1) <em>vs.</em> T<sub>1</sub>: 7.6 (6.4–9.3) <em>vs.</em> T<sub>2</sub>: 8.3 (7.2–11.0), <em>P</em>=0.043}. RR (<em>P</em>=0.409), HR (<em>P</em>=0.417), and SpO<sub>2</sub>/FiO<sub>2</sub> (<em>P</em>=0.262) did not change significantly during prone positioning (PP). The COV moved from the ventral area to the dorsal area (T<sub>0</sub>: 48.8%±6.2% <em>vs.</em> T<sub>1</sub>: 54.8%±6.8% <em>vs.</em> T<sub>2</sub>: 50.3%±6.1%, <em>P</em>=0.030) after APP. The GI decreased significantly after APP (T<sub>0</sub>: median=42.7 %, [IQR: 38.3%–47.5%] <em>vs.</em> T<sub>1</sub>: median=38.2%, [IQR: 34.6%–50.7%] <em>vs.</em> T<sub>2</sub>: median=37.4%, [IQR: 34.2%–41.4%], <em>P</em>=0.049). RVD (<em>P</em>=0.794) did not change after APP.</div></div><div><h3>Conclusions</h3><div>APP can improve ventilation distribution and homogeneity of lung ventilation as assessed by EIT in non-intubated patients with AHRF.</div><div><strong>Trail Registration</strong> C","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 43-50"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This review summarizes the current research advances and guideline updates in neurocritical care. For the therapy of ischemic stroke, the extended treatment time window for thrombectomy and the emergence of novel thrombolytic agents and strategies have brought greater hope for patient recovery. Minimally invasive hematoma evacuation and goal-directed bundled management have shown clinical benefits in treating cerebral hemorrhage. In the treatment of aneurysmal subarachnoid hemorrhage (aSAH), early lumbar drainage can reduce the risk of infarction. Decompressive craniectomy for severe traumatic brain injury has also obtained high-quality evidence support. However, multimodal brain monitoring strategies for patients with traumatic brain injury need further optimization. For patients with cardiac arrest, extracorporeal cardiopulmonary resuscitation can reduce in-hospital mortality and improve long-term neurological prognosis. For neurocritical care patients, abundant high-quality studies have emerged in areas including multimodal neuromonitoring, hemodynamic management, airway management and respiratory therapy, and antiepileptic treatment. In 2023, the guidelines for aSAH have been updated for the first time in the past decade, aiming to provide evidence-based practice recommendations for clinical care. Chinese expert consensuses have also been formulated to guide analgesia and sedation for neurocritical care patients and developed a set of medical quality indicators on neurocritical care, which will enhance standardization and homogenization improvement in neurocritical care quality.
{"title":"Current advances in neurocritical care","authors":"Yuqing Chen , Shuya Wang , Shanshan Xu , Ningyuan Xu , Linlin Zhang , Jianxin Zhou","doi":"10.1016/j.jointm.2024.04.005","DOIUrl":"10.1016/j.jointm.2024.04.005","url":null,"abstract":"<div><div>This review summarizes the current research advances and guideline updates in neurocritical care. For the therapy of ischemic stroke, the extended treatment time window for thrombectomy and the emergence of novel thrombolytic agents and strategies have brought greater hope for patient recovery. Minimally invasive hematoma evacuation and goal-directed bundled management have shown clinical benefits in treating cerebral hemorrhage. In the treatment of aneurysmal subarachnoid hemorrhage (aSAH), early lumbar drainage can reduce the risk of infarction. Decompressive craniectomy for severe traumatic brain injury has also obtained high-quality evidence support. However, multimodal brain monitoring strategies for patients with traumatic brain injury need further optimization. For patients with cardiac arrest, extracorporeal cardiopulmonary resuscitation can reduce in-hospital mortality and improve long-term neurological prognosis. For neurocritical care patients, abundant high-quality studies have emerged in areas including multimodal neuromonitoring, hemodynamic management, airway management and respiratory therapy, and antiepileptic treatment. In 2023, the guidelines for aSAH have been updated for the first time in the past decade, aiming to provide evidence-based practice recommendations for clinical care. Chinese expert consensuses have also been formulated to guide analgesia and sedation for neurocritical care patients and developed a set of medical quality indicators on neurocritical care, which will enhance standardization and homogenization improvement in neurocritical care quality.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 23-31"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141706520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jointm.2024.07.003
Norberto Chavez-Tapia , Muneeba Ahsan Sayeed , Shobha Luxmi , Douglas J. Kasper , Fenchao Xue , Yang Shen , Weiliang Fan , Wei Yuan , Bin Du
Background
Receptor-interacting protein kinase 1 (RIPK1), a serine/threonine protein kinase, is mainly activated by pro-inflammatory cytokines and pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its activation could result in apoptosis, necroptosis, or inflammation. This study was conducted to evaluate the safety and efficacy of a potent and selective inhibitor of RIPK1, SIR1-365, in hospitalized patients with severe coronavirus disease 2019 (COVID-19).
Methods
This multicenter, randomized, double-blind, phase 1b study screened patients from December 18, 2020 until November 27, 2021. Adults hospitalized with severe COVID-19 (diagnosed ≤2 weeks before screening) were randomized 1:1 to receive oral placebo or SIR1-365 100 mg three times daily for ≤14 consecutive days, with standard-of-care. The primary objective was to evaluate SIR1-365 safety and tolerability. Secondary objectives included an assessment of SIR1-365 efficacy. Descriptive statistics were used to summarize safety. The study was not powered for efficacy testing. Relevant inferential statistical tests were used to aid interpretation of differences in clinical efficacy.
Results
Forty-five patients were randomized, 42 were treated. Eighteen patients experienced treatment-emergent adverse events (TEAEs) and 7 patients were ≥ grade 3. Fewer SIR1-365-treated vs. placebo-treated patients experienced TEAEs (30.4% vs. 57.9%) and serious TEAEs (13.0% vs. 26.3%) within 28 days of the first dose. There were no serious treatment-related TEAEs or deaths. Compare to placebo, SIR1-365 significantly increased arterial oxygenation from baseline to day 7 (least-squares mean change [standard error]: 109.4 [26.4] vs. -24.2 [23.6]; P=0.0095), significantly reduced hospitalization duration after treatment (mean±standard deviation: [4.7±3.7] days vs. [8.6±5.6] days; P=0.0145) and respiratory failure incidence (8.3% vs. 38.1%; two-sided P=0.0291) during the study, and numerically shortened the time to clinical improvement in World Health Organization ordinal scale (median: 5.0 days vs. 9.0 days, P=0.0766).
Conclusions
SIR1-365 was well tolerated and demonstrated a trend toward quicker recovery than placebo in hospitalized patients with severe COVID-19.
背景：受体相互作用蛋白激酶1 （Receptor-interacting protein kinase 1, RIPK1）是一种丝氨酸/苏氨酸蛋白激酶，主要被促炎细胞因子和病原体激活，包括严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)，其激活可导致细胞凋亡、坏死或炎症。本研究旨在评估RIPK1强效选择性抑制剂SIR1-365在2019年严重冠状病毒病（COVID-19）住院患者中的安全性和有效性。方法：这项多中心、随机、双盲、1b期研究从2020年12月18日至2021年11月27日筛查患者。因严重COVID-19住院的成人（筛查前诊断≤2周）按1:1随机分组，接受口服安慰剂或SIR1-365 100 mg，每日3次，连续≤14天。主要目的是评估SIR1-365的安全性和耐受性。次要目标包括SIR1-365的疗效评估。采用描述性统计对安全性进行总结。这项研究没有功效测试。使用相关的统计检验来解释临床疗效的差异。结果：随机分组45例，治疗42例。18例患者出现治疗不良事件（teae）， 7例患者≥3级。sir1 -365治疗组与安慰剂治疗组相比，在首次给药后28天内出现teae （30.4% vs 57.9%）和严重teae （13.0% vs 26.3%）的患者较少。没有与治疗相关的严重teae或死亡。与安慰剂相比，SIR1-365从基线到第7天显著增加动脉氧合(最小二乘平均变化[标准误差]:109.4[26.4]对-24.2 [23.6]；P=0.0095)，治疗后住院时间显著缩短(平均±标准差：[4.7±3.7]天vs.[8.6±5.6]天；P=0.0145)和呼吸衰竭发生率(8.3% vs. 38.1%；双侧P=0.0291)，并在数值上缩短了世界卫生组织（World Health Organization）顺序量表的临床改善时间（中位数：5.0天vs. 9.0天，P=0.0766）。结论：SIR1-365耐受性良好，在重症COVID-19住院患者中显示出比安慰剂更快恢复的趋势。临床试验注册。gov号码：NCT04622332。
{"title":"Safety and efficacy of selective RIPK1 inhibitor SIR1-365 in hospitalized patients with severe COVID-19: A multicenter, randomized, double-blind, phase 1b trial","authors":"Norberto Chavez-Tapia , Muneeba Ahsan Sayeed , Shobha Luxmi , Douglas J. Kasper , Fenchao Xue , Yang Shen , Weiliang Fan , Wei Yuan , Bin Du","doi":"10.1016/j.jointm.2024.07.003","DOIUrl":"10.1016/j.jointm.2024.07.003","url":null,"abstract":"<div><h3>Background</h3><div>Receptor-interacting protein kinase 1 (RIPK1), a serine/threonine protein kinase, is mainly activated by pro-inflammatory cytokines and pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its activation could result in apoptosis, necroptosis, or inflammation. This study was conducted to evaluate the safety and efficacy of a potent and selective inhibitor of RIPK1, SIR1-365, in hospitalized patients with severe coronavirus disease 2019 (COVID-19).</div></div><div><h3>Methods</h3><div>This multicenter, randomized, double-blind, phase 1b study screened patients from December 18, 2020 until November 27, 2021. Adults hospitalized with severe COVID-19 (diagnosed ≤2 weeks before screening) were randomized 1:1 to receive oral placebo or SIR1-365 100 mg three times daily for ≤14 consecutive days, with standard-of-care. The primary objective was to evaluate SIR1-365 safety and tolerability. Secondary objectives included an assessment of SIR1-365 efficacy. Descriptive statistics were used to summarize safety. The study was not powered for efficacy testing. Relevant inferential statistical tests were used to aid interpretation of differences in clinical efficacy.</div></div><div><h3>Results</h3><div>Forty-five patients were randomized, 42 were treated. Eighteen patients experienced treatment-emergent adverse events (TEAEs) and 7 patients were ≥ grade 3. Fewer SIR1-365-treated <em>vs</em>. placebo-treated patients experienced TEAEs (30.4% <em>vs.</em> 57.9%) and serious TEAEs (13.0% <em>vs.</em> 26.3%) within 28 days of the first dose. There were no serious treatment-related TEAEs or deaths. Compare to placebo, SIR1-365 significantly increased arterial oxygenation from baseline to day 7 (least-squares mean change [standard error]: 109.4 [26.4] <em>vs.</em> -24.2 [23.6]; <em>P</em>=0.0095), significantly reduced hospitalization duration after treatment (mean±standard deviation: [4.7±3.7] days <em>vs</em>. [8.6±5.6] days; <em>P</em>=0.0145) and respiratory failure incidence (8.3% <em>vs</em>. 38.1%; two-sided <em>P</em>=0.0291) during the study, and numerically shortened the time to clinical improvement in World Health Organization ordinal scale (median: 5.0 days <em>vs.</em> 9.0 days, <em>P</em>=0.0766).</div></div><div><h3>Conclusions</h3><div>SIR1-365 was well tolerated and demonstrated a trend toward quicker recovery than placebo in hospitalized patients with severe COVID-19.</div><div><strong>Trial Registration</strong> ClinicalTrials.gov number: NCT04622332</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 70-78"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jointm.2024.08.001
Geoffroy Hariri , Matthieu Legrand
Acute kidney injury (AKI) presents a significant challenge in the management of critically ill patients, as it is associated with increased mortality, prolonged hospital stays, and increased healthcare costs. In certain conditions, such as during sepsis or after cardiac surgery, AKI is one of the most frequent complications, affecting 30%–50% of patients. Over time, even after the resolution of AKI, it can evolve into chronic kidney disease, a leading global cause of mortality, and cardiovascular complications. Despite significant improvement in the care of critically ill patients over the past two decades, the incidence of AKI remains stable, and novel approaches aiming at reducing its occurrence or improving AKI outcomes are still mostly lacking. However, recent insights into the pathophysiology of AKI within critical care settings have shed light on new pathways for both prevention and treatment, providing various new therapeutic targets aimed to mitigating kidney injury. These advancements highlight the intricate and multifaceted nature of the mechanisms underlying AKI, which could explain the challenge of identifying an effective treatment. Among these targets, modulation of the inflammatory responses and the cellular metabolism, hemodynamic regulation and enhancement of cellular repair mechanisms, have emerged as promising options. These multifaceted approaches offer renewed hope for limiting the incidence and severity of AKI in critically ill patients. Several ongoing clinical trials are evaluating the efficacy of these different strategies and we are facing an exiting time with multiple therapeutic interventions being tested to prevent or treat AKI. In this review, we aim to provide a summary of the new drugs evaluated for preventing or treating AKI in critical care and surgical settings.
{"title":"New drugs for acute kidney injury","authors":"Geoffroy Hariri , Matthieu Legrand","doi":"10.1016/j.jointm.2024.08.001","DOIUrl":"10.1016/j.jointm.2024.08.001","url":null,"abstract":"<div><div>Acute kidney injury (AKI) presents a significant challenge in the management of critically ill patients, as it is associated with increased mortality, prolonged hospital stays, and increased healthcare costs. In certain conditions, such as during sepsis or after cardiac surgery, AKI is one of the most frequent complications, affecting 30%–50% of patients. Over time, even after the resolution of AKI, it can evolve into chronic kidney disease, a leading global cause of mortality, and cardiovascular complications. Despite significant improvement in the care of critically ill patients over the past two decades, the incidence of AKI remains stable, and novel approaches aiming at reducing its occurrence or improving AKI outcomes are still mostly lacking. However, recent insights into the pathophysiology of AKI within critical care settings have shed light on new pathways for both prevention and treatment, providing various new therapeutic targets aimed to mitigating kidney injury. These advancements highlight the intricate and multifaceted nature of the mechanisms underlying AKI, which could explain the challenge of identifying an effective treatment. Among these targets, modulation of the inflammatory responses and the cellular metabolism, hemodynamic regulation and enhancement of cellular repair mechanisms, have emerged as promising options. These multifaceted approaches offer renewed hope for limiting the incidence and severity of AKI in critically ill patients. Several ongoing clinical trials are evaluating the efficacy of these different strategies and we are facing an exiting time with multiple therapeutic interventions being tested to prevent or treat AKI. In this review, we aim to provide a summary of the new drugs evaluated for preventing or treating AKI in critical care and surgical settings.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 3-11"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jointm.2024.05.001
Yuting Li, Youquan Wang, Jianxing Guo, Dong Zhang
Background
The effect of the modality of hydrocortisone administration on clinical outcomes in patients with septic shock remains uncertain. This systematic review and meta-analysis evaluate the impact of intermittent bolus and continuous infusion of hydrocortisone on these outcomes.
Methods
We searched the PubMed, Embase databases, and Cochrane Library for randomized controlled trials (RCTs) and cohort studies published from inception to January 1, 2023. We included studies involving adult patients with septic shock. All authors reported our primary outcome of short-term mortality and clearly compared the clinically relevant secondary outcomes (ICU length of stay, hospital length of stay, vasopressor-free days, hyperglycemia, hypernatremia, and ICU-acquired weakness [ICUAW]) of intermittent bolus and continuous infusion of hydrocortisone. Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). The PROSPERO registration number is CRD42023392160.
Results
Seven studies, including 554 patients, were included. The primary outcome of this meta-analysis showed no statistically significant difference in the short-term mortality between intermittent bolus and continuous infusion groups (OR=1.21, 95% CI: 0.84 to 1.73; P=0.31; Chi2=9.06; I2=34%). Secondary outcomes showed no statistically significant difference in the ICU length of stay (MD=−0.15, 95% CI: −2.31 to 2.02; P=0.89; Chi2=0.95; I2=0%), hospital length of stay (MD=0.63, 95% CI: −4.24 to 5.50; P=0.80; Chi2=0.61; I2=0%), vasopressor-free days (MD=−1.18, 95% CI: −2.43 to 0.06; P=0.06; Chi2=2.48; I2=60%), hyperglycemia (OR=1.27, 95% CI: 0.80 to 2.02; P=0.31; Chi2=5.23; I2=43%), hypernatremia (OR=0.93, 95% CI: 0.44 to 1.96; P=0.85; Chi2=0.37; I2=0%), or ICUAW (OR=0.83, 95% CI: 0.36 to 1.94; P=0.67; Chi2=0.90; I2=0%) between the two groups.
Conclusions
This meta-analysis indicated no significant difference in short-term mortality between intermittent bolus or continuous hydrocortisone infusion in patients with septic shock. Additionally, the hydrocortisone infusion method was not associated with ICU length of stay, hospital length of stay, vasopressor-free days, hyperglycemia, hypernatremia, or ICUAW.
{"title":"Influence of hydrocortisone infusion method on the clinical outcome of patients with septic shock: A systematic review and meta-analysis","authors":"Yuting Li, Youquan Wang, Jianxing Guo, Dong Zhang","doi":"10.1016/j.jointm.2024.05.001","DOIUrl":"10.1016/j.jointm.2024.05.001","url":null,"abstract":"<div><h3>Background</h3><div>The effect of the modality of hydrocortisone administration on clinical outcomes in patients with septic shock remains uncertain. This systematic review and meta-analysis evaluate the impact of intermittent bolus and continuous infusion of hydrocortisone on these outcomes.</div></div><div><h3>Methods</h3><div>We searched the PubMed, Embase databases, and Cochrane Library for randomized controlled trials (RCTs) and cohort studies published from inception to January 1, 2023. We included studies involving adult patients with septic shock. All authors reported our primary outcome of short-term mortality and clearly compared the clinically relevant secondary outcomes (ICU length of stay, hospital length of stay, vasopressor-free days, hyperglycemia, hypernatremia, and ICU-acquired weakness [ICUAW]) of intermittent bolus and continuous infusion of hydrocortisone. Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). The PROSPERO registration number is CRD42023392160.</div></div><div><h3>Results</h3><div>Seven studies, including 554 patients, were included. The primary outcome of this meta-analysis showed no statistically significant difference in the short-term mortality between intermittent bolus and continuous infusion groups (OR=1.21, 95% CI: 0.84 to 1.73; <em>P</em>=0.31; <em>Chi<sup>2</sup></em>=9.06; <em>I</em><sup>2</sup>=34%). Secondary outcomes showed no statistically significant difference in the ICU length of stay (MD=−0.15, 95% CI: −2.31 to 2.02; <em>P</em>=0.89; <em>Chi<sup>2</sup></em>=0.95; <em>I</em><sup>2</sup>=0%), hospital length of stay (MD=0.63, 95% CI: −4.24 to 5.50; <em>P</em>=0.80; <em>Chi<sup>2</sup></em>=0.61; <em>I</em><sup>2</sup>=0%), vasopressor-free days (MD=−1.18, 95% CI: −2.43 to 0.06; <em>P</em>=0.06; <em>Chi<sup>2</sup></em>=2.48; <em>I</em><sup>2</sup>=60%), hyperglycemia (OR=1.27, 95% CI: 0.80 to 2.02; <em>P</em>=0.31; <em>Chi<sup>2</sup></em>=5.23; <em>I</em><sup>2</sup>=43%), hypernatremia (OR=0.93, 95% CI: 0.44 to 1.96; <em>P</em>=0.85; <em>Chi<sup>2</sup></em>=0.37; <em>I</em><sup>2</sup>=0%), or ICUAW (OR=0.83, 95% CI: 0.36 to 1.94; <em>P</em>=0.67; <em>Chi<sup>2</sup></em>=0.90; <em>I</em><sup>2</sup>=0%) between the two groups.</div></div><div><h3>Conclusions</h3><div>This meta-analysis indicated no significant difference in short-term mortality between intermittent bolus or continuous hydrocortisone infusion in patients with septic shock. Additionally, the hydrocortisone infusion method was not associated with ICU length of stay, hospital length of stay, vasopressor-free days, hyperglycemia, hypernatremia, or ICUAW.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 100-107"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer patients who are exposed to sepsis and had previous chemotherapy may have increased severity. Among chemotherapeutic agents, anthracyclines have been associated with cardiac toxicity. Like other chemotherapeutic agents, they may cause endothelial toxicity. The aim of this study was to evaluate the effect of anthracycline treatment on the outcome of cancer patients with sepsis.
Methods
Data from cancer patients admitted to intensive care units (ICUs) for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique database (1994–2015). Comparison between patients who received anthracycline and those who did not was performed using a propensity score, including confounding variables (age and underlying diseases). A competing risk adjusted for severity of illness (Sequential Organ Failure Assessment [SOFA] score) was used to analyze the duration of vasopressor requirement.
Results
Among 2046 patients, 1070 (52.3%) patients who received anthracycline were compared with 976 (47.7%) who did not. The underlying disease was mostly acute hematological malignancy (49.2%). Sepsis, mostly pneumonia (47.7%), had developed 2 days (interquartile range [IQR]:1–4 days) prior to ICU admission. Most patients (n=1156/1980,58.4%) required vasopressors for 3 days (IQR: 2–6 days). Factors associated with the need for vasopressors were aplasia (hazard ratio [HR]=1.72, 95% confidence interval [CI]: 1.21 to 2.47, P=0.002) and day 1 respiratory SOFA score (HR=7.07, 95% CI: 2.75 to 22.1, P <0.001). Previous anthracycline treatment was not associated with an increased risk of vasopressor use. The duration of vasopressors was not different between patients who received anthracycline and those who did not (P=0.79). Anthracycline was not associated with ICU mortality.
Conclusion
Previous anthracycline treatment did not alter the course of sepsis in a cohort of cancer patients admitted to intensive care with sepsis.
背景：暴露于败血症和既往化疗的癌症患者可能会加重严重程度。在化疗药物中，蒽环类药物与心脏毒性有关。像其他化疗药物一样，它们可能引起内皮毒性。本研究的目的是评估蒽环类药物治疗对癌症患者脓毒症预后的影响。方法：从Groupe de Recherche呼吸器组织（Groupe de Recherche呼吸器组织）数据库（1994-2015）中提取重症监护病房（icu）因脓毒症或脓毒性休克住院的癌症患者的数据。使用倾向评分对接受蒽环类药物治疗和未接受蒽环类药物治疗的患者进行比较，包括混杂变量（年龄和潜在疾病）。根据疾病严重程度调整的竞争风险（序贯器官衰竭评估[SOFA]评分）用于分析血管加压药需求的持续时间。结果：2046例患者中，1070例（52.3%）患者接受蒽环类药物治疗，976例（47.7%）患者未接受蒽环类药物治疗。基础疾病多为急性血液系统恶性肿瘤（49.2%）。脓毒症，主要是肺炎（47.7%），发生在ICU入院前2天（四分位数间距[IQR]:1-4天）。大多数患者（n=1156/1980,58.4%）需要血管加压药物治疗3天（IQR: 2-6天）。与血管加压药物需求相关的因素是发育不全（风险比[HR]=1.72, 95%可信区间[CI]: 1.21 ~ 2.47， P=0.002）和第1天呼吸SOFA评分（HR=7.07, 95% CI: 2.75 ~ 22.1， P=0.79）。蒽环类药物与ICU死亡率无关。结论：既往蒽环类药物治疗并未改变一组因脓毒症而入院重症监护的癌症患者的脓毒症病程。
{"title":"Previous treatment with anthracycline does not affect the course of sepsis in cancer patients: Retrospective cohort study","authors":"Windsor Camille , Joseph Adrien , Pons Stephanie , Mokart Djamel , Pène Frederic , Kouatchet Achille , Demoule Alexandre , Bruneel Fabrice , Nyunga Martine , Borcoman Edith , Legrand Matthieu , Darmon Michael , Zafrani Lara , Azoulay Elie , Lemiale Virginie","doi":"10.1016/j.jointm.2024.07.005","DOIUrl":"10.1016/j.jointm.2024.07.005","url":null,"abstract":"<div><h3>Background</h3><div>Cancer patients who are exposed to sepsis and had previous chemotherapy may have increased severity. Among chemotherapeutic agents, anthracyclines have been associated with cardiac toxicity. Like other chemotherapeutic agents, they may cause endothelial toxicity. The aim of this study was to evaluate the effect of anthracycline treatment on the outcome of cancer patients with sepsis.</div></div><div><h3>Methods</h3><div>Data from cancer patients admitted to intensive care units (ICUs) for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique database (1994–2015). Comparison between patients who received anthracycline and those who did not was performed using a propensity score, including confounding variables (age and underlying diseases). A competing risk adjusted for severity of illness (Sequential Organ Failure Assessment [SOFA] score) was used to analyze the duration of vasopressor requirement.</div></div><div><h3>Results</h3><div>Among 2046 patients, 1070 (52.3%) patients who received anthracycline were compared with 976 (47.7%) who did not. The underlying disease was mostly acute hematological malignancy (49.2%). Sepsis, mostly pneumonia (47.7%), had developed 2 days (interquartile range [IQR]:1–4 days) prior to ICU admission. Most patients (<em>n</em>=1156/1980,58.4%) required vasopressors for 3 days (IQR: 2–6 days). Factors associated with the need for vasopressors were aplasia (hazard ratio [HR]=1.72, 95% confidence interval [CI]: 1.21 to 2.47, <em>P</em>=0.002) and day 1 respiratory SOFA score (HR=7.07, 95% CI: 2.75 to 22.1, <em>P</em> <0.001). Previous anthracycline treatment was not associated with an increased risk of vasopressor use. The duration of vasopressors was not different between patients who received anthracycline and those who did not (<em>P</em>=0.79). Anthracycline was not associated with ICU mortality.</div></div><div><h3>Conclusion</h3><div>Previous anthracycline treatment did not alter the course of sepsis in a cohort of cancer patients admitted to intensive care with sepsis.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 64-69"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jointm.2024.05.002
Olcay Dilken , Annemieke Dijkstra , Göksel Güven , Bülent Ergin , Nicole Trommel , Margriet E. van Baar , Helma WC Hofland , Can Ince , Cornelis H. van der Vlies
Background
Severe burns induce volume shifts via capillary leaks, eventually requiring massive fluid resuscitation and promoting tissue edema. Albumin may help to mitigate the edema, thereby improving perfusion. This study shows that sublingual microcirculation measurements can quantify both tissue perfusion and edema.
Methods
This prospective observational study was conducted between November 2018 and December 2019 in the intensive care unit of Maasstad Hospital Burn Center, Rotterdam, The Netherlands. Patients with severe burns affecting >15% of the total body surface area were included. Fluid management was conducted in accordance with the Parkland formula. Albumin (20%) was administered at a rate of 0.5 mL/(kg·h), starting 12 h after the burn incident. Alterations in the sublingual microcirculation, including capillary perfusion and density, were measured at admission (T0) and 4 h (T4) and 12 h (T12) after admission. Sublingual depth of focus (DOF) of the microcirculation was used to quantify the tissue edema.
Results
Nine patients were recruited with a mean total body surface area of 36% ± 23%. By T12, a median of 4085 mL (interquartile range [IQR]: 3714–6756 mL) of crystalloids and 446 mL (IQR: 176–700 mL) of 20% albumin were administered. The DOF increased significantly after crystalloid administration (T4 vs. T0, mean difference [MD]=27.4 µm, 95% confidence interval [CI]: 3.4 to 50.9, P=0.040). Following albumin administration, DOF significantly decreased (T12 vs. T4, MD=−76.4 µm, 95% CI: −116.6 to −36.1, P=0.002). Total vessel density decreased significantly with crystalloid administration (T4 vs. T0, MD=−3.5 mm/mm2, 95% CI: −5.7 to −1.4, P=0.004) but increased after albumin administration (T12 vs. T4, MD=6.2 mm/mm2, 95% CI: 3.2 to 9.3, P=0.001).
Conclusion
Sublingual microcirculation measurement of DOF and other parameters provide a valuable tool for the assessment of tissue perfusion and edema in patients with severe burns. Further investigation is required to evaluate the role of albumin in increasing microcirculatory convection and reducing tissue edema.
背景：严重烧伤通过毛细血管渗漏引起体积变化，最终需要大量液体复苏并促进组织水肿。白蛋白可能有助于减轻水肿，从而改善灌注。本研究表明，舌下微循环测量可以量化组织灌注和水肿。方法本前瞻性观察研究于2018年11月至2019年12月在荷兰鹿特丹Maasstad医院烧伤中心的重症监护室进行。烧伤面积占体表总面积15%的严重烧伤患者纳入研究。流体管理按照帕克兰公式进行。在烧伤后12小时开始，以0.5 mL/（kg·h）的速率给药白蛋白（20%）。入院时（T0）、入院后4 h （T4）和12 h （T12）测量舌下微循环的变化，包括毛细血管灌注和密度。用舌下微循环病灶深度（DOF）来量化组织水肿。结果9例患者入组，平均体表面积36%±23%。到T12时，给药晶体中位数为4085 mL（四分位间距[IQR]: 3714-6756 mL）， 20%白蛋白中位数为446 mL （IQR: 176-700 mL）。晶体给药后DOF显著增加（T4 vs. T0，平均差值[MD]=27.4µm， 95%可信区间[CI]: 3.4 ~ 50.9， P=0.040）。白蛋白给药后，DOF显著降低（T12 vs T4， MD= - 76.4µm, 95% CI: - 116.6 ~ - 36.1， P=0.002）。晶体给药后血管总密度显著降低（T4 vs. T0， MD= - 3.5 mm/mm2, 95% CI: - 5.7 ~ - 1.4， P=0.004），但白蛋白给药后血管总密度增加（T12 vs. T4， MD=6.2 mm/mm2, 95% CI: 3.2 ~ 9.3， P=0.001）。结论舌下微循环DOF等指标的测定为重度烧伤患者组织灌注和水肿的评估提供了有价值的工具。白蛋白在增加微循环对流和减少组织水肿中的作用有待进一步研究。
{"title":"Microcirculatory depth of focus measurement shows reduction of tissue edema by albumin resuscitation in burn patients","authors":"Olcay Dilken , Annemieke Dijkstra , Göksel Güven , Bülent Ergin , Nicole Trommel , Margriet E. van Baar , Helma WC Hofland , Can Ince , Cornelis H. van der Vlies","doi":"10.1016/j.jointm.2024.05.002","DOIUrl":"10.1016/j.jointm.2024.05.002","url":null,"abstract":"<div><h3>Background</h3><div>Severe burns induce volume shifts via capillary leaks, eventually requiring massive fluid resuscitation and promoting tissue edema. Albumin may help to mitigate the edema, thereby improving perfusion. This study shows that sublingual microcirculation measurements can quantify both tissue perfusion and edema.</div></div><div><h3>Methods</h3><div>This prospective observational study was conducted between November 2018 and December 2019 in the intensive care unit of Maasstad Hospital Burn Center, Rotterdam, The Netherlands. Patients with severe burns affecting >15% of the total body surface area were included. Fluid management was conducted in accordance with the Parkland formula. Albumin (20%) was administered at a rate of 0.5 mL/(kg·h), starting 12 h after the burn incident. Alterations in the sublingual microcirculation, including capillary perfusion and density, were measured at admission (T0) and 4 h (T4) and 12 h (T12) after admission. Sublingual depth of focus (DOF) of the microcirculation was used to quantify the tissue edema.</div></div><div><h3>Results</h3><div>Nine patients were recruited with a mean total body surface area of 36% ± 23%. By T12, a median of 4085 mL (interquartile range [IQR]: 3714–6756 mL) of crystalloids and 446 mL (IQR: 176–700 mL) of 20% albumin were administered. The DOF increased significantly after crystalloid administration (T4 <em>vs.</em> T0, mean difference [MD]=27.4 µm, 95% confidence interval [CI]: 3.4 to 50.9, <em>P</em>=0.040). Following albumin administration, DOF significantly decreased (T12 <em>vs.</em> T4, MD=−76.4 µm, 95% CI: −116.6 to −36.1, <em>P</em>=0.002). Total vessel density decreased significantly with crystalloid administration (T4 <em>vs.</em> T0, MD=−3.5 mm/mm<sup>2</sup>, 95% CI: −5.7 to −1.4, <em>P</em>=0.004) but increased after albumin administration (T12 <em>vs.</em> T4, MD=6.2 mm/mm<sup>2</sup>, 95% CI: 3.2 to 9.3, <em>P</em>=0.001).</div></div><div><h3>Conclusion</h3><div>Sublingual microcirculation measurement of DOF and other parameters provide a valuable tool for the assessment of tissue perfusion and edema in patients with severe burns. Further investigation is required to evaluate the role of albumin in increasing microcirculatory convection and reducing tissue edema.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 58-63"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141702563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jointm.2024.10.001
Changsong Wang , Dechang Chen
{"title":"Critical Care Almanac: Annual Innovations and Achievements","authors":"Changsong Wang , Dechang Chen","doi":"10.1016/j.jointm.2024.10.001","DOIUrl":"10.1016/j.jointm.2024.10.001","url":null,"abstract":"","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 1-2"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jointm.2024.07.004
Ran Meng , Zhengzhong Sun , Ruxue Chi , Yan Gu , Yuxiang Zhang , Jiaxing Wang
Background
The roles of the Pink1/Parkin pathway and mitophagy in lung injury during heat stroke remain unclear. In this study, we investigated the role of Pink1/Parkin-mediated mitophagy in acute lung injury (ALI) in rats with exertional heat stroke (EHS).
Methods
Sixty Sprague Dawley rats were randomly divided into control (CON), control + Parkin overexpression (CON + Parkin), EHS, and EHS + Parkin overexpression (EHS + Parkin) groups. Parkin was overexpressed by injecting an adeno-associated virus carrying the Parkin gene into the tail vein, and a rat model of EHS was established. Pathological changes in the lung tissue were analyzed using microcomputed tomography (micro-CT), and the lung coefficient and pulmonary capillary permeability were measured. Enzyme-linked immunosorbent assay were used to determine the levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α, and reactive oxygen species. The morphology of mitochondria in type Ⅱ epithelial cells of lung tissue was observed using transmission electron microscopy; and the apoptosis of lung tissue, the level of mitophagy, and the co-localization of Pink1 and Parkin were determined using immunofluorescence. The expression of Pink1, Parkin, mitofusin-2 (MFN2), phosphatase and tensin homolog (PTEN), PTEN-L, p62, and the autophagy marker microtubule-associated protein 1 light chain 3 (LC3) in rat lung tissue was measured by Western blotting, and the ratio of LC3II/LC3I was calculated.
Results
Compared with the EHS group, the survival rate of rats in the EHS + Parkin group was significantly higher. Their lung coefficient and pulmonary vascular permeability decreased and the pathological changes were significantly alleviated (P <0.05). Their levels of inflammatory factors and reactive oxygen species were significantly decreased (P <0.05), and the degree of mitochondrial swelling in pulmonary type II epithelial cells was alleviated. The apoptosis of lung tissue was alleviated, the colocalization of Pink1 and Parkin, LC3 and Tom20 was enhanced, and the ratio of LC3-II/LC3-I increased. The expression of Pink1, MFN2, PTEN-L, and p62 decreased, whereas the expression of PTEN was not significantly different from that in the EHS group (P >0.05).
Conclusion
Pink1/Parkin-mediated mitophagy dysfunction is one of the mechanisms underlying ALI in rats with EHS, and activation of Parkin overexpression-mediated mitophagy can alleviate ALI caused by EHS.
背景：Pink1/Parkin通路和线粒体自噬在中暑肺损伤中的作用尚不清楚。本研究探讨了Pink1/ parkinson介导的线粒体自噬在运动性中暑（EHS）大鼠急性肺损伤（ALI）中的作用。方法：将60只sd大鼠随机分为对照组（CON）、对照组+ Parkin过表达组（CON + Parkin）、EHS组和EHS + Parkin过表达组（EHS + Parkin）。通过向尾静脉注射携带Parkin基因的腺相关病毒，过表达Parkin，建立EHS大鼠模型。采用微计算机断层扫描（micro-CT）分析肺组织病理变化，测定肺系数和肺毛细血管通透性。采用酶联免疫吸附法测定白细胞介素-6 （IL-6）、IL-1β、肿瘤坏死因子-α和活性氧水平。透射电镜观察肺组织Ⅱ型上皮细胞线粒体形态；免疫荧光法检测肺组织凋亡、线粒体自噬水平以及Pink1和Parkin的共定位。采用Western blotting检测大鼠肺组织中Pink1、Parkin、mitofusin-2 （MFN2）、磷酸酶和紧张素同源物（PTEN）、PTEN- l、p62及自噬标志物微管相关蛋白1轻链3 （LC3）的表达，并计算LC3II/LC3I的比值。结果：与EHS组比较，EHS + Parkin组大鼠存活率明显高于EHS组。大鼠肺系数和肺血管通透性降低，病理改变明显减轻（P P P >0.05）。结论：Pink1/Parkin介导的线粒体自噬功能障碍是EHS大鼠ALI的机制之一，激活Parkin过表达介导的线粒体自噬可减轻EHS引起的ALI。
{"title":"Overexpression of Parkin promotes the protective effect of mitochondrial autophagy on the lung of rats with exertional heatstroke","authors":"Ran Meng , Zhengzhong Sun , Ruxue Chi , Yan Gu , Yuxiang Zhang , Jiaxing Wang","doi":"10.1016/j.jointm.2024.07.004","DOIUrl":"10.1016/j.jointm.2024.07.004","url":null,"abstract":"<div><h3>Background</h3><div>The roles of the Pink1/Parkin pathway and mitophagy in lung injury during heat stroke remain unclear. In this study, we investigated the role of Pink1/Parkin-mediated mitophagy in acute lung injury (ALI) in rats with exertional heat stroke (EHS).</div></div><div><h3>Methods</h3><div>Sixty Sprague Dawley rats were randomly divided into control (CON), control + Parkin overexpression (CON + Parkin), EHS, and EHS + Parkin overexpression (EHS + Parkin) groups. Parkin was overexpressed by injecting an adeno-associated virus carrying the <em>Parkin</em> gene into the tail vein, and a rat model of EHS was established. Pathological changes in the lung tissue were analyzed using microcomputed tomography (micro-CT), and the lung coefficient and pulmonary capillary permeability were measured. Enzyme-linked immunosorbent assay were used to determine the levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α, and reactive oxygen species. The morphology of mitochondria in type Ⅱ epithelial cells of lung tissue was observed using transmission electron microscopy; and the apoptosis of lung tissue, the level of mitophagy, and the co-localization of Pink1 and Parkin were determined using immunofluorescence. The expression of Pink1, Parkin, mitofusin-2 (MFN2), phosphatase and tensin homolog (PTEN), PTEN-L, p62, and the autophagy marker microtubule-associated protein 1 light chain 3 (LC3) in rat lung tissue was measured by Western blotting, and the ratio of LC3II/LC3I was calculated.</div></div><div><h3>Results</h3><div>Compared with the EHS group, the survival rate of rats in the EHS + Parkin group was significantly higher. Their lung coefficient and pulmonary vascular permeability decreased and the pathological changes were significantly alleviated (<em>P</em> <0.05). Their levels of inflammatory factors and reactive oxygen species were significantly decreased (<em>P</em> <0.05), and the degree of mitochondrial swelling in pulmonary type II epithelial cells was alleviated. The apoptosis of lung tissue was alleviated, the colocalization of Pink1 and Parkin, LC3 and Tom20 was enhanced, and the ratio of LC3-II/LC3-I increased. The expression of Pink1, MFN2, PTEN-L, and p62 decreased, whereas the expression of PTEN was not significantly different from that in the EHS group (<em>P</em> >0.05).</div></div><div><h3>Conclusion</h3><div>Pink1/Parkin-mediated mitophagy dysfunction is one of the mechanisms underlying ALI in rats with EHS, and activation of Parkin overexpression-mediated mitophagy can alleviate ALI caused by EHS.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 89-99"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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