Improving ECMO therapy: Monitoring oxygenator functionality and identifying key indicators, factors, and considerations for changeout.

INTRODUCTION: The optimal timing for extracorporeal membrane oxygenation (ECMO) circuit change-out is crucial for the successful management of patients with severe cardiopulmonary failure. This comprehensive review examines the various factors that influence the timing of oxygenator replacement in the ECMO circuit. By considering these factors, clinicians can make informed decisions to ensure timely and effective change-out, enhancing patient outcomes and optimizing the delivery of ECMO therapy. METHODOLOGY: A thorough search of relevant studies on ECMO circuits and oxygenator change-out was conducted using multiple scholarly databases and relevant keywords. Studies published between 2017 and 2023 were included, resulting in 40 studies that met the inclusion criteria. DISCUSSION: Thrombosis within the membrane oxygenator and its impact on dysfunction were identified as significant contributors, highlighting the importance of monitoring coagulation parameters and gas exchange. Several factors, including fibrinogen levels, pre and post-membrane blood gases, plasma-free hemoglobin, D-dimers, platelet function, flows and pressures, and anticoagulation strategy, were found to be important considerations when determining the need for an oxygenator or circuit change-out. The involvement of a multidisciplinary team and thorough preparation were also highlighted as crucial aspects of this process. CONCLUSION: In conclusion, managing circuit change-outs in ECMO therapy requires considering factors such as fibrinogen levels, blood gases, plasma-free hemoglobin, D-dimers, platelet function, flows, pressures, and anticoagulation strategy. Monitoring these parameters allows for early detection of issues, timely interventions, and optimized ECMO therapy. Standardized protocols, personalized anticoagulation approaches, and non-invasive monitoring techniques can improve the safety and effectiveness of circuit change-outs. Further research and collaboration are needed to advance ECMO management and enhance patient outcomes.

Advocating for an open communication culture in perfusion and cardiothoracic community: a call to action.

This article advocates for an open communication culture in the perfusion and cardiothoracic community to enhance patient safety during surgery. All team members, including nurses, anesthesiologists, and perfusionists, should actively contribute their insights. Empowering perfusionists to voice concerns without fear of repercussions is crucial. Involvement in debriefs, root cause analyses and data management systems aids continuous improvement. A robust speak-up culture prevents unsafe practices and elevates perfusion care standards, leading to better patient outcomes.

A multipurpose Extracorporeal Life Support Circuit: a concept for multiorgan transplant and circulatory support service Healthcare provider.

The demand for efficient and adaptable life support systems in the field of Extracorporeal Life Support (ECLS) is steadily increasing. To meet this growing need, there is a requirement for a versatile extracorporeal life support circuit that can be effectively applied in various medical scenarios, especially in tertiary hospitals where multiple ECLS services are utilized. These services include Extracorporeal Membrane Oxygenation (ECMO) for addressing respiratory or cardiac problems, Ventricular Assist Device (VAD) as a bridge to recovery or heart transplant, and Venovenous Bypass (VVB) for assisting liver transplantation. In light of this, we propose the creation of a multipurpose circuit that integrates multiple extracorporeal life support (ECLS) functions to cater to diverse medical needs. This innovative circuit not only offers cost-effectiveness and enhanced safety but also ensures optimal utilization, thereby revolutionizing the realm of life support technologies.

Anticancer L-Asparaginase and Phytoactive Compounds From Plant Solanum nigrum Against MDR (Methicillindrug resistant) Staphylococcus aureus and Fungal Isolates.

L-asparaginase is used in chemotherapy for acute lymphoblastic leukemia and other cancers. L-asparaginase derived from bacterial source triggers immune responses. The current study investigates Solanum nigrum as a novel and latent source of L-asparaginase to minimize immunological reactions. The antitumor activity of SN methanol extract was determined using the potato disc assay. InterPro Chimera and InterPro were used to predict the amino acid sequence of L-asparaginase and its anticancer activity. Purification of the enzyme was carried out to homogeneity of 1.51-fold with a recovery of 61.99%. At optimal conditions of 36.5°C, pH 8.6, and 8.5 g/mL substrate, fruit (crude extract) revealed an L-asparaginase titer of 48.23 U/mL. The molecular weight of the enzyme was calculated to be 32 ± 5 kDa using SDS PAGE. The fruit's total flavonoids and phenolic contents are 0.42 ± .030 g/mL and 94 ± 1.9 mg CAE, respectively. Anti-tumorigenic efficacy was determined to be 66% against Agrobacterium tumefaciens. Additionally, the extract possesses potent antifungal and antibacterial properties. Molecular docking provided the structural motifs and underlying interactions between L-asparaginase, N-acetylglucosamine, murine, and chitin. SN contains high levels of the enzyme L-asparaginase and phytochemicals, making it a potential source of anticancer drugs.

Cognitive outcomes after unruptured intracranial aneurysm treatment with endovascular coiling.

BACKGROUND: We aimed to determine the effects of endovascular coiling of unruptured intracranial aneurysms (UIAs) on cognition to inform treatment decisions. We present the first study using the Montreal Cognitive Assessment (MoCA) to determine neurocognitive changes after endovascular coiling. METHODS: We prospectively collected data on all patients with UIAs undergoing endovascular coiling, primary or assisted. Patients completed the MoCA prior to intervention and 1 month and 6 months' post-procedure. A repeated measures linear mixed effects model was used to compare pre-procedure and post-procedure cognition. RESULTS: Thirty-three patients with 33 aneurysms who underwent coiling from April 2017 to May 2020 were included (mean age 55.5, 81.8% female). All procedures used general anesthesia. There was no difference between baseline and post-procedure MoCA scores at any time interval (P>0.05). Mean MoCA scores at baseline, 1 month post-procedure, and 6 months' post-procedure were 25.4, 26.8, and 26.3 respectively. There was also no difference between pre- and post-procedure scores on any individual MoCA domain (visuospatial, naming, memory, attention, language, abstraction, delayed recall, and orientation) at any time interval (P>0.05). Seventeen patients had follow-up MRI or CT imaging, of which 11.8% showed radiographic changes or ischemia. 77.8% of patients with 6-month angiographic follow-up achieved class I, and 22.2% achieved class II Raymond-Roy Occlusion. Thirty-two out of 33 patients had follow-up mRS ≤2. CONCLUSION: Our study suggests that endovascular coiling does not diminish neurocognitive function. Patients with UIAs in our cohort also had baseline MoCA scores below the cut-off for mild cognitive impairment despite pre-procedure mRS and NIHSS of 0.

Comparison of First-Pass Efficacy Among Four Mechanical Thrombectomy Techniques: A Single-Center Experience.

BACKGROUND: First-pass efficacy (FPE) is an established marker of technical and clinical efficacy among mechanical thrombectomy (MT) techniques. It is unclear what the optimal approach is in achieving FPE. We present a single-center experience comparing rates of FPE among 2 MT techniques and evaluate the potential predictors of FPE among other outcomes. METHODS: A single-center retrospective analysis was carried out of patients with consecutive large-vessel occlusion strokes (LVOS) of anterior circulation from September 2015 to April 2019 who underwent MT and for whom data were available on the status of FPE. Four MT techniques were identified: ADAPT (a direct first-pass aspiration), SrADAPT (stent retriever with aspiration), SRBG (stent retriever with balloon guide catheter), and STRAP (stent retriever-aspiration and proximal flow arrest). The primary outcome was FPE and secondary outcomes included the rate of successful reperfusion. RESULTS: Among 226 patients with LVOS of the anterior circulation who underwent MT, data were available for 164 on FPE for the 4 MT techniques. SRBG was the most prevalent technique. No significant difference was found in rates of FPE among the 4 MT techniques (P = 0.332). No independent predictors of FPE were identified on multivariable analysis. STRAP had the highest rate of successful reperfusion compared with the other techniques (P = 0.049) and was the only independent predictor of that outcome (P = 0.027). CONCLUSIONS: Among patients with LVOS of the anterior circulation, the rate of FPE did not differ among the 4 MT techniques. There were no predictors of FPE among the studied variables. STRAP was the only predictor of successful reperfusion.

MDM2 as a target for ellagic acid­mediated suppression of prostate cancer cells in vitro.

Prostate cancer (PCa) is the most common cancer in men. Despite the available treatments for PCa, a significant number of patients relapse as the disease becomes hormonal­independent. p53 is a common tumor suppressor; however, its activity is diminished via the overexpression of murine double minute­2 (MDM2). The pomegranate, walnuts, and blueberries are widely consumed fruits and nuts that contain several polyphenolic compounds, mainly ellagic acid (EA). The present study focused on the influence of EA on the p53/MDM2 pathway in PCa cell lines. Three human PCa cell lines PCa LNCaP (p53+/+), 22RV1 (p53-/+), and PC3 (p53-/-) harboring different p53 genotypes were used in this research. We found that EA downregulated the gene and protein expression levels of MDM2 and increased the protein expression of p53 as determined by qPCR and western blot analyses. Moreover, by using western blot analysis, we determined that EA increased the protein expression of the p53 target proteins p21, p53 upregulated modulator of apoptosis (PUMA) [also known as Bcl­2­binding component 3 (BBC3)] and Phorbol­12­myristate­13­acetate­induced protein 1 (NOXA). Furthermore, we found that EA induced apoptosis in the absence of p53 by downregulating MDM2 and X­linked inhibitor of apoptosis protein (XIAP) protein expressions as determined by western blot analysis. We conclude that EA suppressed PCa cells in vitro partly by downregulating MDM2.

Acute Neurological Deterioration in Large Vessel Occlusions and Mild Symptoms Managed Medically.

Background and Purpose- It is unclear which factors predict acute neurological deterioration in patients with large vessel occlusion and mild symptoms. We aim to evaluate the frequency, timing, and potential predictors of acute neurological deterioration ≥4 National Institutes of Health Stroke Scale (NIHSS) points in medically managed patients with large vessel occlusion and mild presentation. Methods- Single-center retrospective study of patients with consecutive minor stroke (defined as NIHSS score of ≤5 on presentation) and large vessel occlusion from January 2014 to December 2017. Primary outcome was acute neurological deterioration ≥4 NIHSS points during the hospitalization. Secondary outcomes included ΔNIHSS (defined as discharge minus admission NIHSS score). Results- Among 1133 patients with acute minor strokes, 122 (10.6%) had visible occlusions on computed tomography angiography/magnetic resonance angiography. Twenty-four (19.7%) patients had ≥4 points deterioration on NIHSS at a median of 3.6 (1-16) hours from arrival. No clinical or radiological predictors of acute neurological deterioration ≥4 NIHSS points were observed on multivariable analysis. Rescue endovascular thrombectomy was performed more often in the ones with acute neurological deterioration ≥4 NIHSS points compared with patients with no deterioration (54% versus 0%; P<0.001). Acute neurological deterioration ≥4 NIHSS points was associated with ΔNIHSS ≥4 points (33% versus 4.9%; P<0.01) and a trend toward lower independence rates at discharge (50% versus 70%; P=0.06) compared with the group with no deterioration. In patients with any degree of neurological worsening, patients who underwent rescue thrombectomy were more likely to be independent at discharge (73% versus 38%; P=0.02) and to have a favorable ΔNIHSS (-2 [-3 to 0] versus 0 [-1 to 6]; P=0.05) compared with the ones not offered rescue thrombectomy. Conclusions- Acute neurological deterioration ≥4 NIHSS points was observed in a fifth of patients with large vessel occlusion and mild symptoms, occurred very early in the hospital course, impacted functional outcomes, and could not be predicted by any of the studied clinical and radiological variables. Rescue thrombectomy was associated with improved clinical outcomes at discharge in patients with neurological deterioration.

A Comparative Analysis of Machine/Deep Learning Models for Parking Space Availability Prediction.

Machine/Deep Learning (ML/DL) techniques have been applied to large data sets in order to extract relevant information and for making predictions. The performance and the outcomes of different ML/DL algorithms may vary depending upon the data sets being used, as well as on the suitability of algorithms to the data and the application domain under consideration. Hence, determining which ML/DL algorithm is most suitable for a specific application domain and its related data sets would be a key advantage. To respond to this need, a comparative analysis of well-known ML/DL techniques, including Multilayer Perceptron, K-Nearest Neighbors, Decision Tree, Random Forest, and Voting Classifier (or the Ensemble Learning Approach) for the prediction of parking space availability has been conducted. This comparison utilized Santander's parking data set, initiated while working on the H2020 WISE-IoT project. The data set was used in order to evaluate the considered algorithms and to determine the one offering the best prediction. The results of this analysis show that, regardless of the data set size, the less complex algorithms like Decision Tree, Random Forest, and KNN outperform complex algorithms such as Multilayer Perceptron, in terms of higher prediction accuracy, while providing comparable information for the prediction of parking space availability. In addition, in this paper, we are providing Top-K parking space recommendations on the basis of distance between current position of vehicles and free parking spots.

Urolithin A induces prostate cancer cell death in p53-dependent and in p53-independent manner.

PURPOSE: Pomegranate and walnuts are widely consumed dietary sources and contain several bioactive compounds, including the ellagitannins (ETs). ETs are polyphenols that are metabolized in the gut microbiota to urolithin A (UA). p53 is a tumor suppressor that lost its activity through MDM2 activation in about half cancers. The purpose of this study was to investigate the influence of UA on the p53-MDM2 interaction pathway in prostate cancer cell lines. METHODS: Three human prostate cancer cell lines were used that harbor different p53 genotypes; LNCaP (p53+/+), 22RV1(p53-/+) and PC3 (p53-/-). Cell viability was determined by CellTiter-Glo Luminescent assay. Apoptosis was confirmed by measuring annexin V by flow cytometry. The expression of p53, its target proteins, and apoptotic markers were measured by western blotting. Real-time qPCR was used to measure the gene expression of p21, a main target gene of p53. Co-immunoprecipitation-immunoblotting was used to assess the inhibition of interactions between p53 and MDM2 and to assess the effect of UA on MDM2-mediated p53 polyubiquitination. RESULTS: We found UA inhibited CaP cells' viability and induced apoptosis. For 22RV1 and LNCaP, we found UA increased p53 protein expression and its main target protein, p21, and MDM2, forming an autoregulatory feedback loop. In addition, UA increased the p53 proapoptotic proteins PUMA and NOXA. Moreover, UA inhibited the interaction between p53 and MDM2 and inhibited MDM2-mediated p53 polyubiquitination. UA downregulated MDM2 and XIAP protein expression in PC3 cells and upregulated p21 and p14ARF in a p53-independent manner. CONCLUSION: The influencing of UA on p53-MDM2 pathway may partly contribute to its anticancer effect.

Cognitive outcomes after unruptured intracranial aneurysm treatment with flow diversion.

OBJECTIVE: Flow diversion is increasingly used to treat a variety of intracranial aneurysms with good safety and efficacy; however, there is some evidence that this treatment is associated with a larger postoperative ischemic burden on imaging than that with other traditional endovascular modalities. These findings typically do not manifest as neurological deficits, but any subtle effects on cognition remain unknown. In this study, the authors describe the neurocognitive performance of a cohort of patients with unruptured intracranial aneurysms (UIAs) before and after treatment with flow diversion. This is the first report of cognitive outcomes following aneurysm treatment with flow diversion. METHODS: The authors prospectively collected data on cognitive function using the Montreal Cognitive Assessment (MoCA) tool in patients with UIAs who were undergoing endovascular aneurysm treatment with flow diversion between June 2017 and July 2019. Patients completed the MoCA prior to intervention, at the 1-month follow-up after treatment, and again at 6 months after the procedure. All patients with UIAs treated with flow diversion were included regardless of age, aneurysm location, or morphology, unless their functional status precluded completion of the MoCA instrument. A repeated-measures linear mixed-effects model was used to compare preintervention and postintervention cognitive status at the time intervals outlined. RESULTS: Fifty-one patients with 61 aneurysms underwent endovascular aneurysm treatment with flow diversion (mean age 52.5 years, 90.2% females). There was no difference between baseline and postprocedure MoCA scores at any time interval (p > 0.05). The MoCA scores at baseline, 1 month postprocedure, and 6 months postprocedure were 26.1, 26.2, and 26.6, respectively. There was also no difference between pre- and postprocedure scores on any individual domain of the instrument (visuospatial, naming, attention, language, abstraction, delayed recall, and orientation) at any time interval (p > 0.05). Thirty-four patients had follow-up MRI or CT imaging, 5 of whom showed radiographic changes or ischemia. All patients with follow-up clinical evaluation had a 6-month modified Rankin Scale score ≤ 2. CONCLUSIONS: Flow diversion is increasingly used in the treatment of intracranial aneurysms. This study suggests that this treatment may not alter neurocognitive function. Larger patient samples and longer follow-ups with other tests of cognitive functions are needed to confirm these findings.

The international POTS registry: Evaluating the efficacy of an exercise training intervention in a community setting.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) affects primarily young women and impairs quality of life. We found that in a research setting, exercise training along with lifestyle intervention is effective as a nondrug therapy for POTS. OBJECTIVE: To evaluate the efficacy of our exercise training/lifestyle intervention in POTS patients in a community environment. METHODS: We established a POTS registry and enrolled 251 patients (86% women, aged 26 ± 11 [SD] years) through their physicians. A 3-month program involving mild- to moderate-intensity endurance training (progressing from semirecumbent to upright, 3-5 times/wk, 30-45 min/session) plus strength training was implemented along with increasing salt/water intake. The program was delivered to the physicians, who oversaw training in their patients. A 10-minute stand test was performed at the physician's office and patient quality of life was assessed using the 36-Item Short Form Health Survey. RESULTS: One hundred and three patients completed the program. Of those that completed, 71% no longer qualified for POTS and were thus in remission. The increase in heart rate from supine to 10-minute stand was markedly lower (23 ± 14 vs. 46 ± 17 beats/min before intervention; P < .001), while patient quality of life was improved dramatically after intervention (P < .001). Of those who were followed for 6-12 months (n = 31), the effect was persistent. CONCLUSIONS: A training/lifestyle intervention program can be implemented in a community setting with physician supervision and is effective in the treatment of POTS. It remains to be determined whether exercise can be an effective long-term treatment strategy for this condition, though patients are encouraged to maintain an active lifestyle indefinitely.

Association of a favorable cardiovascular health profile with the presence of coronary artery calcification.

BACKGROUND: To examine the association between the American Heart Association's 7 metrics of ideal cardiovascular health (ICH) and the presence of subclinical coronary atherosclerosis as assessed by coronary artery calcification (CAC) using electron-beam computed tomography. METHODS AND RESULTS: This study is a cross-sectional analysis of data obtained on 3121 male and female patients evaluated at the Cooper Clinic in Dallas, Texas, between 1997 and 2007. We included men aged ≥45 and women aged ≥55 without known cardiovascular disease and for whom information on all ICH metrics and a CAC score were available. Patients were grouped into 3 categories according to their number of ICH metrics: favorable (4-7 ICH metrics), intermediate (3 metrics), and unfavorable (0-2 metrics). Patients with favorable ICH profiles had a lower prevalence and severity of subclinical atherosclerosis than those with unfavorable or intermediate ICH profiles as estimated by CAC. This inverse association of CAC with ICH metrics was evident whether the presence of coronary calcium was defined as CAC score>0, CAC score>100, or CAC score>400. Patients with favorable ICH profiles had odds of coronary calcium (CAC>0) less than half of those for patients with unfavorable profiles (odds ratio 0.41; 95% confidence interval, 0.34-0.50) and patients with intermediate ICH profiles had odds of detectable CAC 32% lower (odds ratio 0.68; 95% confidence interval, 0.57-0.82). CONCLUSIONS: A statistically significant association was found between a favorable level of ICH metrics and less or absent subclinical atherosclerosis as measured by CAC underscoring the importance of primordial prevention.