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Objective: We aimed to determine if machine learning can predict acute brain injury and to identify modifiable risk factors for acute brain injury in patients receiving venoarterial extracorporeal membrane oxygenation. Methods: We included adults (age ≥18 years) receiving venoarterial extracorporeal membrane oxygenation or extracorporeal cardiopulmonary resuscitation in the Extracorporeal Life Support Organization Registry (2009-2021). Our primary outcome was acute brain injury: central nervous system ischemia, intracranial hemorrhage, brain death, and seizures. We used Random Forest, CatBoost, LightGBM, and XGBoost machine learning algorithms (10-fold leave-1-out cross-validation) to predict and identify features most important for acute brain injury. We extracted 65 total features: demographics, pre-extracorporeal membrane oxygenation/on-extracorporeal membrane oxygenation laboratory values, and pre-extracorporeal membrane oxygenation/on-extracorporeal membrane oxygenation settings. Results: Of 35,855 patients receiving venoarterial extracorporeal membrane oxygenation (nonextracorporeal cardiopulmonary resuscitation) (median age of 57.8 years, 66% were male), 7.7% (n = 2769) experienced acute brain injury. In venoarterial extracorporeal membrane oxygenation (nonextracorporeal cardiopulmonary resuscitation), the area under the receiver operator characteristic curves to predict acute brain injury, central nervous system ischemia, and intracranial hemorrhage were 0.67, 0.67, and 0.62, respectively. The true-positive, true-negative, false-positive, false-negative, positive, and negative predictive values were 33%, 88%, 12%, 67%, 18%, and 94%, respectively, for acute brain injury. Longer extracorporeal membrane oxygenation duration, higher 24-hour extracorporeal membrane oxygenation pump flow, and higher on-extracorporeal membrane oxygenation partial pressure of oxygen were associated with acute brain injury. Of 10,775 patients receiving extracorporeal cardiopulmonary resuscitation (median age of 57.1 years, 68% were male), 16.5% (n = 1787) experienced acute brain injury. The area under the receiver operator characteristic curves for acute brain injury, central nervous system ischemia, and intracranial hemorrhage were 0.72, 0.73, and 0.69, respectively. Longer extracorporeal membrane oxygenation duration, older age, and higher 24-hour extracorporeal membrane oxygenation pump flow were associated with acute brain injury. Conclusions: In the largest study predicting neurological complications with machine learning in extracorporeal membrane oxygenation, longer extracorporeal membrane oxygenation duration and higher 24-hour pump flow were associated with acute brain injury in nonextracorporeal cardiopulmonary resuscitation and extracorporeal cardiopulmonary resuscitation venoarterial extracorporeal membrane oxygenation.

Early detection of acute brain injury (ABI) is critical to intensive care unit (ICU) patient management and intervention to decrease major complications. Head CT (HCT) is the standard of care for the assessment of ABI in ICU patients; however, it has limited sensitivity compared to MRI. We retrospectively compared the ability of ultra-low-field portable MR (ULF-pMR) and head HCT, acquired within 24 h of each other, to detect ABI in ICU patients supported on extracorporeal membrane oxygenation (ECMO). A total of 17 adult patients (median age 55 years; 47% male) were included in the analysis. Of the 17 patients assessed, ABI was not observed on either ULF-pMR or HCT in eight patients (47%). ABI was observed in the remaining nine patients with a total of 10 events (8 ischemic, 2 hemorrhagic). Of the eight ischemic events, ULF-pMR observed all eight, while HCT only observed four events. Regarding hemorrhagic stroke, ULF-pMR observed only one of them, while HCT observed both. ULF-pMR outperformed HCT for the detection of ABI, especially ischemic injury, and may offer diagnostic advantages for ICU patients. The lack of sensitivity to hemorrhage may improve with modification of the imaging acquisition program.

Background: Despite the high prevalence of neurological complications and mortality associated with extracorporeal cardiopulmonary resuscitation (ECPR), neurologically-focused animal models are scarce. Our objective is to review current ECPR models investigating neurological outcomes and identify key elements for a recommended model. Methods: We searched PubMed and four other engines for animal ECPR studies examining neurological outcomes. Inclusion criteria were: animals experiencing cardiac arrest, ECPR/ECMO interventions, comparisons of short versus long cardiac arrest times, and neurological outcomes. Results: Among 20 identified ECPR animal studies (n = 442), 13 pigs, 4 dogs, and 3 rats were used. Only 10% (2/20) included both sexes. Significant heterogeneity was observed in experimental protocols. 90% (18/20) employed peripheral VA-ECMO cannulation and 55% (11/20) were survival models (median survival = 168 hours; ECMO duration = 60 minutes). Ventricular fibrillation (18/20, 90%) was the most common method for inducing cardiac arrest with a median duration of 15 minutes (IQR = 6–20). In two studies, cardiac arrests exceeding 15 minutes led to considerable mortality and neurological impairment. Among seven studies utilizing neuromonitoring tools, only four employed multimodal devices to evaluate cerebral blood flow using Transcranial Doppler ultrasound and near-infrared spectroscopy, brain tissue oxygenation, and intracranial pressure. None examined cerebral autoregulation or neurovascular coupling. Conclusions: The substantial heterogeneity in ECPR preclinical model protocols leads to limited reproducibility and multiple challenges. The recommended model includes large animals with both sexes, standardized pre-operative protocols, a cardiac arrest time between 10–15 minutes, use of multimodal methods to evaluate neurological outcomes, and the ability to survive animals after conducting experiments.

Extracorporeal membrane oxygenation (ECMO), in conjunction with its life-saving benefits, carries a significant risk of acute brain injury (ABI). Hypoxic-ischemic brain injury (HIBI) is one of the most common types of ABI in ECMO patients. Various risk factors, such as history of hypertension, high day 1 lactate level, low pH, cannulation technique, large peri-cannulation PaCO2 drop (∆PaCO2), and early low pulse pressure, have been associated with the development of HIBI in ECMO patients. The pathogenic mechanisms of HIBI in ECMO are complex and multifactorial, attributing to the underlying pathology requiring initiation of ECMO and the risk of HIBI associated with ECMO itself. HIBI is likely to occur in the peri-cannulation or peri-decannulation time secondary to underlying refractory cardiopulmonary failure before or after ECMO. Current therapeutics target pathological mechanisms, cerebral hypoxia and ischemia, by employing targeted temperature management in the case of extracorporeal cardiopulmonary resuscitation (eCPR), and optimizing cerebral O2 saturations and cerebral perfusion. This review describes the pathophysiology, neuromonitoring, and therapeutic techniques to improve neurological outcomes in ECMO patients in order to prevent and minimize the morbidity of HIBI. Further studies aimed at standardizing the most relevant neuromonitoring techniques, optimizing cerebral perfusion, and minimizing the severity of HIBI once it occurs will improve long-term neurological outcomes in ECMO patients.

Docetaxel (DTX)-loaded polymeric micelles (DTBM) were formulated using the triblock copolymer, poly(ethylene glycol)–polylactide–poly(ethylene glycol) (PEG–PLA–PEG), to comprehensively study their pharmaceutical application as anticancer nanomedicine. DTBM showed a stable formulation of anticancer nanomedicine that could be reconstituted after lyophilization (DTBM-R) in the presence of PEG 2000 and D-mannitol (Man) as surfactant and protectant, respectively. DTBM-R showed a particle size less than 150 nm and greater than 90% of DTX recovery after reconstitution. The robustly formed micelles might minimize systemic toxicity due to their sustained drug release and also maximize antitumor efficacy through increased accumulation and release of DTX from the micelles. From the pharmaceutical development point of view, DTBM-R showing successful reconstitution could be considered as a potent nanomedicine for tumor treatment.

Nanotechnology-based photo-chemo combination therapy has been extensively investigated to improve therapeutic outcomes in anticancer treatment. Specifically, with the help of a singlet oxygen generated by the photosensitizer, the endocytosed nanoparticles are allowed to escape from the endosomal compartment, which is currently an obstacle in nanotechnology-based anticancer therapy. In this study, a liposomal complex system (Lipo (Pep, Ce6)), composed of a chlorin e6-conjugated di-block copolymer (PEG-PLL(-g-Ce6)) and a D-(KLAKLAK)2 peptide loading liposome (Lipo (Pep)), was developed and evaluated for its anticancer activity. Due to the membrane lytic ability of the D-(KLAKLAK)2 peptide and the membrane disruptive effect of the singlet oxygen generated from chlorin e6, Lipo (Pep, Ce6) accelerated the disruption of the endosomal compartment, and exhibited strong synergistic anticancer activity in vitro. The prepared liposomal complex system could potentially maximize the efficacy of the nanotechnology-based photo-chemo combination therapy, and can be regarded as a novel, versatile strategy in advanced tumor therapy.