Journal of intensive medicine最新文献

{"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}

{"title":"New drugs for acute kidney injury","authors":"Geoffroy Hariri ,&nbsp;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}

{"title":"Influence of hydrocortisone infusion method on the clinical outcome of patients with septic shock: A systematic review and meta-analysis","authors":"Yuting Li,&nbsp;Youquan Wang,&nbsp;Jianxing Guo,&nbsp;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>Chi²</em>=9.06; <em>I</em>²=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>Chi²</em>=0.95; <em>I</em>²=0%), hospital length of stay (MD=0.63, 95% CI: −4.24 to 5.50; <em>P</em>=0.80; <em>Chi²</em>=0.61; <em>I</em>²=0%), vasopressor-free days (MD=−1.18, 95% CI: −2.43 to 0.06; <em>P</em>=0.06; <em>Chi²</em>=2.48; <em>I</em>²=60%), hyperglycemia (OR=1.27, 95% CI: 0.80 to 2.02; <em>P</em>=0.31; <em>Chi²</em>=5.23; <em>I</em>²=43%), hypernatremia (OR=0.93, 95% CI: 0.44 to 1.96; <em>P</em>=0.85; <em>Chi²</em>=0.37; <em>I</em>²=0%), or ICUAW (OR=0.83, 95% CI: 0.36 to 1.94; <em>P</em>=0.67; <em>Chi²</em>=0.90; <em>I</em>²=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}

{"title":"Previous treatment with anthracycline does not affect the course of sepsis in cancer patients: Retrospective cohort study","authors":"Windsor Camille ,&nbsp;Joseph Adrien ,&nbsp;Pons Stephanie ,&nbsp;Mokart Djamel ,&nbsp;Pène Frederic ,&nbsp;Kouatchet Achille ,&nbsp;Demoule Alexandre ,&nbsp;Bruneel Fabrice ,&nbsp;Nyunga Martine ,&nbsp;Borcoman Edith ,&nbsp;Legrand Matthieu ,&nbsp;Darmon Michael ,&nbsp;Zafrani Lara ,&nbsp;Azoulay Elie ,&nbsp;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> &lt;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}

{"title":"Microcirculatory depth of focus measurement shows reduction of tissue edema by albumin resuscitation in burn patients","authors":"Olcay Dilken ,&nbsp;Annemieke Dijkstra ,&nbsp;Göksel Güven ,&nbsp;Bülent Ergin ,&nbsp;Nicole Trommel ,&nbsp;Margriet E. van Baar ,&nbsp;Helma WC Hofland ,&nbsp;Can Ince ,&nbsp;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 &gt;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/mm², 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/mm², 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}

{"title":"Critical Care Almanac: Annual Innovations and Achievements","authors":"Changsong Wang ,&nbsp;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}

{"title":"Overexpression of Parkin promotes the protective effect of mitochondrial autophagy on the lung of rats with exertional heatstroke","authors":"Ran Meng ,&nbsp;Zhengzhong Sun ,&nbsp;Ruxue Chi ,&nbsp;Yan Gu ,&nbsp;Yuxiang Zhang ,&nbsp;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> &lt;0.05). Their levels of inflammatory factors and reactive oxygen species were significantly decreased (<em>P</em> &lt;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> &gt;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}

{"title":"Nebulized aminoglycosides for ventilator-associated pneumonia: Methodological considerations and lessons from experimental studies","authors":"Jean-Jacques Rouby ,&nbsp;Jing Xia ,&nbsp;Jayesh Dhanani ,&nbsp;Gianluigi Li Bassi ,&nbsp;Antoine Monsel ,&nbsp;Antoni Torres","doi":"10.1016/j.jointm.2024.07.006","DOIUrl":"10.1016/j.jointm.2024.07.006","url":null,"abstract":"<div><div>Aminoglycosides are concentration-dependent antibiotics exerting a bactericidal effect when concentrations at the site of infection are equal to or greater than 5 times the minimum inhibitory concentrations (MIC). When administered intravenously, they exhibit poor lung penetration and high systemic renal and ototoxicity, imposing to restrict their administration to 5 days. Experimental studies conducted in anesthetized and mechanically ventilated sheep and pigs provide evidence that high doses of nebulized aminoglycosides induce a rapid and potent bacterial killing in the infected lung parenchyma. They also confirm that the alveolar-capillary membrane, either normal or injured by the infectious process, restricts the penetration of intravenous aminoglycosides in the infected lung parenchyma, precluding a bactericidal effect at the site of infection. However, injury of the alveolar-capillary membrane promotes the systemic diffusion of nebulized aminoglycosides. Based on experimental data obtained in animals with inoculation pneumonia, it challenges the classical belief that nebulization protects against systemic toxicity. Loss of lung aeration decreases the lung penetration of nebulized aminoglycosides. Nevertheless, lung tissue concentrations measured in non-aerated lung regions with severe and extended pneumonia are most often greater than 5 times the MICs, resulting in a bactericidal effect followed by a progressive pulmonary reaeration. It is likely that the penetration into the consolidated lung, results from the bronchial diffusion of nebulized aminoglycosides toward adjacent non-aerated infected alveolar spaces and their penetration into mechanical ventilation-induced intraparenchymal pseudocysts and distended bronchioles. In animals receiving nebulized aminoglycosides, epithelial lining fluid concentrations grossly overestimate lung interstitial fluid concentrations because of the bronchial contamination of the distal tip of the bronchoscope during the bronchoalveolar procedures. Lung microdialysis is the only technique able to accurately assess lung pharmacokinetics in animals with inoculation pneumonia treated by nebulized aminoglycosides. In 2024, the European Investigators Network for Nebulized Antibiotics in Ventilator-associated Pneumonia (ENAVAP) called for the creation of an international research network for Lung Microdialysis applied to Nebulized Antibiotics (LUMINA) to promote multicentered, experimental, randomized, and controlled studies addressing lung pharmacokinetics of intravenous vs. nebulized antibiotics, using different dosing and ventilator settings.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 12-22"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054395","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":"Intestine-derived fibroblast growth factor 19 alleviates lipopolysaccharide-induced liver injury by regulating bile acid homeostasis and directly improving oxidative stress","authors":"Xiaomeng Tang ,&nbsp;Jingjing Ning ,&nbsp;Yilin Zhao ,&nbsp;Shuyun Feng ,&nbsp;Lujing Shao ,&nbsp;Tiantian Liu ,&nbsp;Huijie Miao ,&nbsp;Yucai Zhang ,&nbsp;Chunxia Wang","doi":"10.1016/j.jointm.2024.06.003","DOIUrl":"10.1016/j.jointm.2024.06.003","url":null,"abstract":"<div><h3>Background</h3><div>Cholestasis plays a critical role in sepsis-associated liver injury (SALI). Intestine-derived fibroblast growth factor 19 (FGF19) is a key regulator for bile acid homeostasis. However, the roles and underlying mechanisms of FGF19 in SALI are still unclear.</div></div><div><h3>Methods</h3><div>We conducted a case–control study that included 58 pediatric patients aged from 1 month to 14-years-old diagnosed with sepsis at Shanghai Children's Hospital from January to December 2018 and 30 healthy individuals. The serum FGF19 levels of these patients with sepsis were analyzed and compared with those of healthy controls. Recombinant human FGF19 was intravenously injected in mice once a day for 7 days at a dose of 0.1 mg/kg body weight before lipopolysaccharide (LPS) treatment. Liver bile acid profiles and the gene expression involved in bile acid homeostasis were investigated in the mice groups. Metabolomic data were further integrated and analyzed using Ingenuity Pathways Analysis (IPA) software. In the <em>in vitro</em> analysis using HepG2 cells, the influence of FGF19 pretreatment on reactive oxygen species (ROS) production and mitochondrial dysfunction was analyzed. Compound C (CC), an inhibitor of AMP-activated protein kinase (AMPK) activation, was used to confirm the roles of AMPK activation in FGF19-mediated hepatoprotective effects.</div></div><div><h3>Results</h3><div>Serum FGF19 levels were significantly lower in children with sepsis than in healthy controls (115 pg/mL <em>vs</em>. 79 pg/mL, <em>P</em>=0.03). Pre-administration of recombinant human FGF19 alleviated LPS-induced acute liver injury (ALI) and improved LPS-induced cholestasis in mice. Moreover, FGF19 directly reversed LPS-induced intracellular ROS generation and LPS-decreased mitochondrial membrane potential <em>in vitro</em> and <em>in vivo</em>, resulting in hepatoprotection against LPS-induced apoptosis. More importantly, the inhibition of AMPK activity partially blocked the protective effects of FGF19 against LPS-induced oxidative stress and mitochondrial dysfunction.</div></div><div><h3>Conclusions</h3><div>Intestine-derived FGF19 alleviates LPS-induced ALI via improving bile acid homeostasis and directly suppressing ROS production via activating the AMPK signaling pathway.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 79-88"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054393","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":"Large language models in critical care","authors":"Laurens A. Biesheuvel ,&nbsp;Jessica D. Workum ,&nbsp;Merijn Reuland ,&nbsp;Michel E. van Genderen ,&nbsp;Patrick Thoral ,&nbsp;Dave Dongelmans ,&nbsp;Paul Elbers","doi":"10.1016/j.jointm.2024.12.001","DOIUrl":"10.1016/j.jointm.2024.12.001","url":null,"abstract":"<div><div>The advent of chat generative pre-trained transformer (ChatGPT) and large language models (LLMs) has revolutionized natural language processing (NLP). These models possess unprecedented capabilities in understanding and generating human-like language. This breakthrough holds significant promise for critical care medicine, where unstructured data and complex clinical information are abundant. Key applications of LLMs in this field include administrative support through automated documentation and patient chart summarization; clinical decision support by assisting in diagnostics and treatment planning; personalized communication to enhance patient and family understanding; and improving data quality by extracting insights from unstructured clinical notes. Despite these opportunities, challenges such as the risk of generating inaccurate or biased information “hallucinations”, ethical considerations, and the need for clinician artificial intelligence (AI) literacy must be addressed. Integrating LLMs with traditional machine learning models – an approach known as Hybrid AI – combines the strengths of both technologies while mitigating their limitations. Careful implementation, regulatory compliance, and ongoing validation are essential to ensure that LLMs enhance patient care rather than hinder it. LLMs have the potential to transform critical care practices, but integrating them requires caution. Responsible use and thorough clinician training are crucial to fully realize their benefits.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 2","pages":"Pages 113-118"},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724785","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}