Journal of intensive medicine最新文献

{"title":"Title Page","authors":"","doi":"10.1016/S2667-100X(25)00007-6","DOIUrl":"10.1016/S2667-100X(25)00007-6","url":null,"abstract":"","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 2","pages":"Pages i-ii"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724783","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}

{"title":"Potential causal association between gut microbiota, inflammatory cytokines, and acute pancreatitis: A Mendelian randomization study","authors":"Xiaofeng Wang ,&nbsp;Yiwen Qiu ,&nbsp;Ying Di ,&nbsp;Hou Shaohua ,&nbsp;Wei Wu ,&nbsp;Weiyi Wang ,&nbsp;Huan Liu ,&nbsp;Pu Li","doi":"10.1016/j.jointm.2024.10.004","DOIUrl":"10.1016/j.jointm.2024.10.004","url":null,"abstract":"<div><h3>Background</h3><div>Acute pancreatitis (AP) ranks among the most frequently encountered gastrointestinal diseases in the emergency department. Recent studies have increasingly emphasized the substantial connection among gut microbiota, inflammatory cytokines, and AP.</div></div><div><h3>Methods</h3><div>A two-sample Mendelian randomization (MR) study was conducted using summary statistics of gut microbiota (GM) from the largest available meta-analysis of genome-wide association studies conducted by the MiBioGen consortium (<em>n</em>=18,340). For cytokines, the data were obtained from a study that investigated genome variant associations with 41 inflammatory cytokines and growth factors (<em>n</em>=8293). The summary statistics of AP were obtained from the FinnGen consortium version R5 data (3022 cases and 195,144 controls). The inverse variance weighted (IVW) method was used as the main analysis, with MR–Egger and weighted median as complementary analytical methods. Sensitivity analyses were performed using Cochran's <em>Q</em>-test, MR–Egger intercept test, leave-one-out analyses, and MR–PRESSO. In addition, we employed the reverse MR analysis and MR Steiger method to estimate the orientations of exposure and outcome.</div></div><div><h3>Result</h3><div>Among the 211 examined GM taxa, the IVW method revealed that Bacteroidales (odds ratio [OR]=1.412, 95% confidence interval [CI]:1.057 to 1.885, <em>P</em>=0.019), <em>Eubacterium fissicatena</em> group (OR=1.240, 95% CI:1.045 to 1.470, <em>P</em>=0.014), and Coprococcus3 (OR=1.481, 95 % CI:1.049 to 2.090, <em>P</em>=0.026) exhibited a positive association with AP. Conversely, Prevotella9 (OR=0.821, 95% CI:0.680 to 0.990, <em>P</em>=0.038), RuminococcaceaeUCG004 (OR=0.757, 95% CI:0.577 to 0.994, <em>P</em>=0.045), and Ruminiclostridium6 (OR=0.696, 95% CI:0.548 to 0.884, <em>P</em>=0.003) displayed a negative correlation with AP. Among the 41 inflammatory cytokines, only macrophage colony-stimulating factor (M_CSF, OR=0.894, 95% CI:0.847 to 0.943, <em>P</em>=0.037) exhibited a negative association with AP. Sensitivity analyses revealed no evidence of pleiotropy or heterogeneity. Nevertheless, the mediation analysis showed that M_CSF did not act as a mediating factor.</div></div><div><h3>Conclusion</h3><div>This two-sample MR study revealed causal associations between specific GM and inflammatory cytokines with AP, respectively. However, inflammatory cytokines did not appear to act as mediating factors in the pathway from GM to AP.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 2","pages":"Pages 185-192"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724779","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}

{"title":"Causes of fulminant tropical probable myocarditis: A retrospective cohort study in the French West Indies","authors":"Laurent Camous ,&nbsp;Nicolas Paulo ,&nbsp;Frederic Martino ,&nbsp;Sylvaine Bastian ,&nbsp;Marc Valette ,&nbsp;Jean-David Pommier","doi":"10.1016/j.jointm.2024.07.001","DOIUrl":"10.1016/j.jointm.2024.07.001","url":null,"abstract":"","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 111-112"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054388","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}

{"title":"Outcomes and risk factors of transported patients with extracorporeal membrane oxygenation: An ECMO center experience","authors":"Lingjuan Liu ,&nbsp;Dingji Hu ,&nbsp;Tong Hao ,&nbsp;Shanshan Chen ,&nbsp;Lei Chen ,&nbsp;Yike Zhu ,&nbsp;Chenhui Jin ,&nbsp;Jing Wu ,&nbsp;Haoya Fu ,&nbsp;Haibo Qiu ,&nbsp;Yi Yang ,&nbsp;Songqiao Liu","doi":"10.1016/j.jointm.2024.04.003","DOIUrl":"10.1016/j.jointm.2024.04.003","url":null,"abstract":"<div><h3>Background</h3><div>Extracorporeal membrane oxygenation (ECMO) has been proven to be a support method and technology for patients with cardiopulmonary failure. However, the transport of patients under ECMO support is challenging given the high-risk technical maneuvers and patient-care concerns involved. Herein, we examined the safety of ECMO during the transport of critically ill patients and its impact on mortality rates, to provide more secure and effective transport strategies in clinical practice.</div></div><div><h3>Method</h3><div>To assess the safety of ECMO patient transport, this study conducted a retrospective analysis on critically ill adults who required ECMO support and transport at the intensive care unit (ICU) center between 2017 and 2023. The study utilized standard ECMO transport protocols and conducted a comprehensive statistical analysis of the collected clinical data and transport processes. The 28-day survival rate for ECMO patients was determined using Kaplan–Meier analysis, while logistic regression identified prognostic factors.</div></div><div><h3>Result</h3><div>Out of 303 patients supported with ECMO, 111 (36.6%) were transported. 69.4% of the transport group were male, mean age was (42.0±17.0) years, mean body mass index was (24.4±4.6) kg/m², and veno-arterial-ECMO accounted for 52.5%. The median transportation distance was 190 (interquartile range [IQR]: 70–260) km, and the longest distance was 8100 km. The median transit time was 180 (IQR: 100–260) min, and the maximum duration was 1720 min. No severe adverse events including death or mechanical failure occurred during transportation. The 28-day survival rate was 64.7% (<em>n</em>=196) and ICU survival rate was 56.1% (<em>n</em>=170) for the entire cohort; whereas, the 28-day survival rate was 72.1% (<em>n</em>=80) and ICU survival rate was 66.7% (<em>n</em>=74) in the transport group. A non-significant difference in 28-day survival was observed between the two groups after propensity score matching (<em>P</em>=0.56). Additionally, we found that acute physiology and chronic health evaluation II score (odds ratio [OR]=1.06, <em>P</em> &lt;0.01), lactate levels (&gt;5 mmol/L, OR=2.80, <em>P</em>=0.01), and renal replacement therapy initiation (OR=3.03, <em>P</em> &lt;0.01) were associated with increased mortality risk.</div></div><div><h3>Conclusion</h3><div>Transporting patients on ECMO between medical facilities is a safe procedure that does not increase patient mortality rates, provided it is orchestrated and executed by proficient transport teams. The prognostic outcome for these patients is predominantly influenced by their pre-existing medical conditions or by complications that may develop during the course of ECMO therapy. These results form the basis for the creation of specialized ECMO network hubs within healthcare regions.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 35-42"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141396556","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}

{"title":"A modified screening protocol for ARDS in patients with respiratory support based on SpO2 and FiO2: A single-center prospective, observational study","authors":"Yan Xia ,&nbsp;Qiancheng Xu ,&nbsp;Zhiyuan Guo ,&nbsp;Huijuan Zhang ,&nbsp;Yingya Cao ,&nbsp;Yupeng Qi ,&nbsp;Qun Chen ,&nbsp;Weihua Lu","doi":"10.1016/j.jointm.2024.06.002","DOIUrl":"10.1016/j.jointm.2024.06.002","url":null,"abstract":"<div><h3>Background</h3><div>The purpose is to formulate a modified screening protocol for acute respiratory distress syndrome (ARDS) in patients with respiratory support based on saturation of pulse oximetry (SpO₂) and inspired oxygen concentration (FiO₂).</div></div><div><h3>Methods</h3><div>This prospective observational study was conducted from August to October 2020 at the Department of Critical Care Medicine of Yijishan Hospital Affiliated with Wannan Medical College. All patients admitted during the study period and required arterial blood gas analysis and electrocardiogram monitoring were included in this study. Patients with contraindications to arterial puncture, methemoglobinemia, carbon monoxide poisoning, and other factors that could affect data collection were excluded. The demographic and clinical data, immediate percutaneous SpO₂, FiO₂, arterial oxygen partial pressure (PaO₂), and respiratory rate were recorded; and the SpO₂/FiO₂ ratio (SFR) and PaO₂/FiO₂ ratio (PFR) values were calculated according to the above information. The patients were divided into two cohorts by random number table: the establishment cohort and the verification cohort. In the established part, data were divided into group H and group N according to whether SpO₂ &gt;97 %. For group H (SpO₂ ≤97 %), the regression equation was established between SFR and PFR. For group N (SpO₂ &gt;97 %), the correlation between each observation data and PFR was analyzed. Then, a new diagnostic process was established, and the reliability was verified with the Berlin definition set as the gold standard for diagnosis and classification.</div></div><div><h3>Results</h3><div>There were 341 patients were included. Among them, 161 patients were used to establish the model, and 180 patients were used to verify the validity of the model. In this new diagnosis progress, when SpO₂ ≤97 %, if SFR ≤352, ARDS may exist; when SpO₂ &gt;97 %, if FiO_2min &gt;39 %, there may be ARDS. The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of the new diagnosis progress for ARDS were 91.1 %, 76.7 %, 89.6 %, 79.6 %, and 83.9 %, respectively.</div></div><div><h3>Conclusion</h3><div>The SpO₂/FiO₂ ratio demonstrates notable sensitivity and specificity in diagnosing ARDS, presenting as a credible alternative to PFR.</div><div><strong>Trail Registration</strong> Chinese Clinical Trial Registry Identifier: ChiCTR2000029217</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 51-57"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054384","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}

{"title":"The pros and cons of beta-blockers in sepsis: Where do we stand in 2024?","authors":"Daniel De Backer ,&nbsp;Dechang Chen","doi":"10.1016/j.jointm.2024.07.002","DOIUrl":"10.1016/j.jointm.2024.07.002","url":null,"abstract":"","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 32-34"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054420","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}

{"title":"Metabolomic profiling and prognostication in COVID-19 acute respiratory distress syndrome","authors":"David Furfaro ,&nbsp;Xiaoyu Che ,&nbsp;Wenhao Gou ,&nbsp;Matthew J. Cummings ,&nbsp;Nischay Mishra ,&nbsp;Daniel Brodie ,&nbsp;Thomas Briese ,&nbsp;Oliver Fiehn ,&nbsp;W. Ian Lipkin ,&nbsp;Max R. O'Donnell","doi":"10.1016/j.jointm.2024.04.001","DOIUrl":"10.1016/j.jointm.2024.04.001","url":null,"abstract":"","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 108-110"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141037971","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}

{"title":"Current advances in neurocritical care","authors":"Yuqing Chen ,&nbsp;Shuya Wang ,&nbsp;Shanshan Xu ,&nbsp;Ningyuan Xu ,&nbsp;Linlin Zhang ,&nbsp;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}

{"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 ,&nbsp;Changxing Chen ,&nbsp;Zhanqi Zhao ,&nbsp;Puyu Deng ,&nbsp;Chenchen Zhang ,&nbsp;Yu Zhang ,&nbsp;Hui Lv ,&nbsp;Daonan Chen ,&nbsp;Hui Xie ,&nbsp;Ruilan Wang","doi":"10.1016/j.jointm.2024.07.007","DOIUrl":"10.1016/j.jointm.2024.07.007","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;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&lt;sub&gt;2&lt;/sub&gt;]/inspired oxygen concentration [FiO&lt;sub&gt;2&lt;/sub&gt;] &lt;200 mmHg or oxygen saturation [SpO&lt;sub&gt;2&lt;/sub&gt;]/FiO&lt;sub&gt;2&lt;/sub&gt; &lt;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&lt;sub&gt;0&lt;/sub&gt;), 30 min after the start of APP (T&lt;sub&gt;1&lt;/sub&gt;), and 30 min returning to supine position after the APP (T&lt;sub&gt;2&lt;/sub&gt;). Clinical parameters like SpO&lt;sub&gt;2&lt;/sub&gt;, respiratory rate (RR), FiO&lt;sub&gt;2&lt;/sub&gt;, heart rate (HR), and ROX (the ratio of SpO&lt;sub&gt;2&lt;/sub&gt; as measured by pulse oximetry/FiO&lt;sub&gt;2&lt;/sub&gt; to RR) were also recorded simultaneously at T&lt;sub&gt;0&lt;/sub&gt;, T&lt;sub&gt;1&lt;/sub&gt;, and T&lt;sub&gt;2&lt;/sub&gt;. 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 &lt;em&gt;post hoc&lt;/em&gt; multiple comparisons.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Ten patients were enrolled. The PaO&lt;sub&gt;2&lt;/sub&gt;/FiO&lt;sub&gt;2&lt;/sub&gt; 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&lt;sub&gt;0&lt;/sub&gt;: 7.5 (6.0–10.1) &lt;em&gt;vs.&lt;/em&gt; T&lt;sub&gt;1&lt;/sub&gt;: 7.6 (6.4–9.3) &lt;em&gt;vs.&lt;/em&gt; T&lt;sub&gt;2&lt;/sub&gt;: 8.3 (7.2–11.0), &lt;em&gt;P&lt;/em&gt;=0.043}. RR (&lt;em&gt;P&lt;/em&gt;=0.409), HR (&lt;em&gt;P&lt;/em&gt;=0.417), and SpO&lt;sub&gt;2&lt;/sub&gt;/FiO&lt;sub&gt;2&lt;/sub&gt; (&lt;em&gt;P&lt;/em&gt;=0.262) did not change significantly during prone positioning (PP). The COV moved from the ventral area to the dorsal area (T&lt;sub&gt;0&lt;/sub&gt;: 48.8%±6.2% &lt;em&gt;vs.&lt;/em&gt; T&lt;sub&gt;1&lt;/sub&gt;: 54.8%±6.8% &lt;em&gt;vs.&lt;/em&gt; T&lt;sub&gt;2&lt;/sub&gt;: 50.3%±6.1%, &lt;em&gt;P&lt;/em&gt;=0.030) after APP. The GI decreased significantly after APP (T&lt;sub&gt;0&lt;/sub&gt;: median=42.7 %, [IQR: 38.3%–47.5%] &lt;em&gt;vs.&lt;/em&gt; T&lt;sub&gt;1&lt;/sub&gt;: median=38.2%, [IQR: 34.6%–50.7%] &lt;em&gt;vs.&lt;/em&gt; T&lt;sub&gt;2&lt;/sub&gt;: median=37.4%, [IQR: 34.2%–41.4%], &lt;em&gt;P&lt;/em&gt;=0.049). RVD (&lt;em&gt;P&lt;/em&gt;=0.794) did not change after APP.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;APP can improve ventilation distribution and homogeneity of lung ventilation as assessed by EIT in non-intubated patients with AHRF.&lt;/div&gt;&lt;div&gt;&lt;strong&gt;Trail Registration&lt;/strong&gt; 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}

{"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 ,&nbsp;Muneeba Ahsan Sayeed ,&nbsp;Shobha Luxmi ,&nbsp;Douglas J. Kasper ,&nbsp;Fenchao Xue ,&nbsp;Yang Shen ,&nbsp;Weiliang Fan ,&nbsp;Wei Yuan ,&nbsp;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}