Central versus peripheral VA ECMO for cardiogenic shock: an 8-year experience of a tertiary cardiac surgery center in Greece.

BACKGROUND: VA ECMO has emerged as an effective rescue therapy in patients with cardiogenic shock refractory to standard treatment protocols and its use is rising worldwide in the last decade. Although experience and availability are growing, outcomes remain poor. There is need for evidence to ameliorate clinical practice and improve outcomes. METHODS: We retrospectively reviewed the medical records of all patients who were supported with VA ECMO for cardiogenic shock at our institution between January 2015 and January 2023. The study purpose was to compare outcomes between patients who were supported with central versus peripheral configuration. RESULTS: ECMO was applied in 108 patients of whom central configuration in 48 (44%) and peripheral in 60 (56%). Patients supported with central VA ECMO were more likely to be supported for post cardiotomy shock [OR 4.6 (CI 95% 2.03 - 10.41)], while patients in the peripheral group for chronic heart failure decompensation [OR 9.4 (CI 95% 1.16 - 76.3]. Central VA ECMO had worse survival during ECMO support (29.2% vs 51.7%, p=0.018) and at discharge (8% vs 37%, p=0.001). These patients were at high risk of complications, such as acute kidney injury (AKI), [OR 2.37 (CI 95% 1.06 - 5.3), p = 0.034] and major bleeding [OR 3.08 (CI 95% 1.36 - 6.94), p<0.001]. CONCLUSIONS: Patients on central VA ECMO were supported mainly for post cardiotomy shock, presented with more complications such as major bleeding and AKI and had worse survival to hospital discharge, compared with patients on peripheral VA ECMO. Patient selection, timing of implementation, cannulation strategy and configuration remain main determinants of clinical outcome.

Prognostic Survey of ECPELLA in Japanese Patients With Acute Myocardial Infarction and Cardiogenic Shock　- Findings From the Japanese Registry for Percutaneous Ventricular Assist Device (J-PVAD).

BACKGROUND: The short-term mortality associated with veno-arterial extracorporeal membrane oxygenation combined with the Impella device (termed ECPELLA) for acute myocardial infarction complicated by cardiogenic shock (AMI-CS) remains unclear. METHODS AND RESULTS: The Japanese Registry for Percutaneous Ventricular Assist Devices (J-PVAD) includes data on all patients treated with an Impella in Japan. We extracted data for 922 AMI-CS patients who underwent ECPELLA support and conducted an exploratory analysis focusing on 30-day mortality. The median age of patients was 69 years, and 83.8% were male. The overall 30-day mortality was 46.1%. Factors associated with mortality included age >80 years, in-hospital cardiac arrest, systolic blood pressure <90 mmHg, serum creatinine >1.5 mg/dL, and serum lactate >4.0 mmol/L. In patients aged >80 years with any of these factors, mortality was significantly higher than in those without, ranging from 57.5% to 64.9%. The J-PVAD score assigns 1 point per predictor, with a C-statistic of 0.620 (95% confidence interval 0.586-0.654). The 30-day mortality was 20.0% for a J-PVAD score of 0, increasing to 70.0% for a score of 5. CONCLUSIONS: The J-PVAD data indicate high short-term mortality in AMI-CS patients treated with ECPELLA, particularly among older patients. Further studies are needed to validate this risk stratification in this patient subset.

A comparative study of femoral artery and combined femoral and axillary artery cannulation in veno-arterial extracorporeal membrane oxygenation patients.

Objective: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a critical support technique for cardiac surgery patients. This study compares the outcomes of femoral artery cannulation vs. combined femoral and axillary artery cannulation in post-cardiotomy VA-ECMO patients. This study aimed to compare the clinical outcomes of critically ill patients post-cardiac surgery under VA-ECMO support using different cannulation strategies. Specifically, the focus was on the impact of femoral artery (FA) cannulation vs. combined femoral artery and axillary artery (FA+AA) cannulation on patient outcomes. Methods: Through a retrospective analysis, we compared 51 adult patients who underwent cardiac surgery and received VA-ECMO support based on the cannulation strategy employed-FA cannulation in 27 cases vs. FA+AA cannulation in 24 cases. Results: The FA+AA group showed significant advantages over the FA group in terms of the incidence of chronic renal failure (CRF) (37.50% vs. 14.81%, p = 0.045), preoperative blood filtration requirement (37.50% vs. 11.11%, p = 0.016), decreased platelet count (82.67 ± 44.95 vs. 147.33 ± 108.79, p = 0.014), and elevated creatinine (Cr) levels (151.80 ± 60.73 vs. 110.26 ± 57.99, p = 0.041), although the two groups had similar 30-day mortality rates (FA group 40.74%, FA+AA group 33.33%). These findings underscore that a combined approach may offer more effective hemodynamic support and better clinical outcomes when selecting an ECMO cannulation strategy. Conclusion: Despite the FA+AA group patients presenting with more preoperative risk factors, this group has exhibited lower rates of complications and faster recovery during ECMO treatment. While there has been no significant difference in 30-day mortality rates between the two cannulation strategies, the FA+AA approach may be more effective in reducing complications and improving limb ischemia. These findings highlight the importance of individualized treatment strategies and meticulous monitoring in managing post-cardiac surgery ECMO patients.

Successful nonsurgical therapeutic management in a case of early mechanical aortic prosthetic thrombosis and coronary embolism after a modified Bentall procedure.

Prosthetic valve thrombosis, although rare, is a life-threatening complication of valve replacement surgery. The authors present an atypical case of a modified Bentall procedure with the CarboSeal Valsalva™ conduit complicated by an early mechanical prosthetic aortic valve thrombosis and coronary embolism. The patient was successfully treated with an emergency percutaneous coronary angioplasty and intracoronary thrombus aspiration of the left anterior descending artery, followed by a systemic 10 mg bolus of tissue plasminogen activator followed by ultraslow (25 h) infusion of low-dose (25 mg), while supported with venoarterial extracorporeal membrane oxygenation.

[Box: see text].

Peripheral-to-central extracorporeal corporeal membrane oxygenation switch in refractory cardiogenic shock patients: outcomes and bridging strategies.

BACKGROUND: Peripheral veno-arterial extracorporeal membrane oxygenation (pECMO) has become the first-line device in refractory cardiogenic shock (rCS). Some pECMO complications can preclude any bridging strategies and a peripheral-to-central ECMO (cECMO) switch can be considered as a bridge-to-decision. We conducted this study to appraise the in-hospital survival and the bridging strategies in patients undergoing peripheral-to-central ECMO switch. METHODS: This retrospective monocenter study included patients admitted to a ECMO-dedicated intensive care unit from February 2006 to January 2023. Patients with rCS requiring pECMO switched to cECMO were included. Patients were not included when the cECMO was the first mechanical circulatory support. RESULTS: Eighty patients, with a median [IQR25-75] age of 44 [29-53] years at admission and a female-to-male sex ratio of 0.6 were included in the study. Refractory pulmonary edema was the main switching reason. Thirty patients (38%) were successfully bridged to: heart transplantation (n = 16/80, 20%), recovery (n = 10/80, 12%) and ventricle assist device (VAD, n = 4/30, 5%) while the others died on cECMO (n = 50/80, 62%). The most frequent complications were the need for renal replacement therapy (76%), hemothorax or tamponade (48%), need for surgical revision (34%), mediastinitis (28%), and stroke (28%). The in-hospital and one-year survival rates were 31% and 27% respectively. Myocardial infarction as the cause of the rCS was the only variable independently associated with in-hospital mortality (HR 2.5 [1.3-4.9], p = 0.009). CONCLUSIONS: The switch from a failing pECMO support to a cECMO as a bridge-to-decision is a possible strategy for a very selected population of young patients with a realistic chance of heart function recovery or heart transplantation. In this setting, cECMO allows patients triage preventing from wasting expensive and limited resources.

Severe stress cardiomyopathy following spinal corrective surgery for scoliosis complicated with pectus excavatum: a case report.

BACKGROUND: Stress cardiomyopathy (SCM) is an acute heart failure syndrome characterized by transient, usually reversible left ventricular systolic dysfunction with normal or enhanced basal compensatory wall motion abnormalities involving the left ventricular anterior septum and apex, resulting in a "ballooning" appearance. However, it has rarely been reported in patients undergoing spinal surgery. CASE PRESENTATION: We report a case of severe stress cardiomyopathy in a scoliosis patient with pectus excavatum who underwent spinal corrective surgery. During the wake-up period, circulatory collapse occurred. After multidisciplinary consultation, the patient was diagnosed with stress cardiomyopathy. At last, she had a good prognosis after a series of treatments including ECMO. CONCLUSION: Stress cardiomyopathy is a reversible but uncommon condition. It can cause death if it is not diagnosed in time. Consequently, this report should improve the awareness of orthopedists and anesthesiologists for timely identification and management. For patients with potential risk factors, timely preoperative intervention should be performed to reduce the occurrence of stress cardiomyopathy.

Successful management of pulmonary hemorrhage from lung carcinoid, in a patient on VenoArterial extracorporeal membrane oxygenation support.

INTRODUCTION: A young man was referred to our Center for refractory cardiogenic shock, accompanied with uncontrolled atrial flutter of unknown duration. The patient was supported with VenoArterial Extracorporeal Membrane Oxygenation (VA ECMO) and Intra-Aortic Balloon Pump (IABP) as a bridge to decision. CASE REPORT: His course was complicated by pulmonary hemorrhage due to an unknown endobronchial mass. A low-grade typical carcinoid without metastases was revealed during work up. He was treated successfully with bronchoscopy-guided interventional therapies and cavo-tricuspid isthmus ablation. Mechanical support was successfully weaned off and 3 months after discharge, he was asymptomatic with no sign of residual tumor. DISCUSSION: Endobronchial treatment is a parenchyma-preserving alternative to surgery, with a comparable recurrence rate, especially in patients with typical carcinoid. CONCLUSION: This is the first case report describing the successful management of pulmonary hemorrhage due to lung carcinoid, in a patient supported with VA ECMO for cardiogenic shock.

Intraoperative Tumor Migration During Renal Tumor Excision, Veno-Arterial Extracorporeal Membrane Oxygenation (V-A ECMO), and Mechanical Thrombectomy with FlowTriever.

We describe a case of a 76-year-old male with stage 3 renal cell carcinoma and known thrombus burden in his inferior vena cava (IVC) who presented for a scheduled radical right open nephrectomy with regional lymph node dissection and IVC thrombectomy. During this procedure, the patient went into pulseless-electrical activity. A trans-esophageal echocardiogram showed thrombus transit into the right atria. Emergent initiation of veno-arterial extracorporeal membrane oxygenation and mechanical embolectomy using a FlowTriever retrieval catheter was required. The patient remained intubated in critical but stable condition. Shortly afterward, he expired due to subsequent complications of massive hemorrhage and disseminated intravascular coagulopathy.

Percutaneous femoral venoarterial ECMO decannulation at the bedside using the Manta vascular closure device.

A case of peripheral venoarterial extracorporeal membrane oxygenation decannulation using the Teleflex Manta vascular closure device is presented.

Extraction of phenolic acids and tetramethylpyrazine in Shanxi aged vinegar base on vortex-assisted liquid-liquid microextraction-hydrophobic deep eutectic solvent: COSMO-RS calculations and ANN-GA optimization.

In this study, vortex-assisted liquid-liquid microextraction (VA-LLME) based on hydrophobic deep eutectic solvents (HDES) was used to efficiently and sustainably extract five phenolic acids and tetramethylpyrazine (TMP) from Shanxi aged vinegar (SAV). The VA-LLME technique was employed to investigate the extraction mechanism of HDES with the best extraction performance for the target compounds using a conductor-like screening model for real solvents (COSMO-RS). An artificial neural network combined with a genetic algorithm (ANN-GA) was developed to optimize the extraction conditions based on single-factor and response surface methodology, while also analyzing the interactive effects on the phenolic acids and TMP in the extracted solution during the extraction phase. The optimized conditions were determined, and the greenness of the procedure was evaluated using an analytical greenness metric, indicating that this technique can serve as a green alternative for the determination of phenolic acids and TMP in SAV.

Kinetic analysis of prothrombinase assembly and substrate delivery mechanisms.

Prothrombinase complex, composed of coagulation factors Xa (FXa) and Va (FVa) is a major enzyme of the blood coagulation network that produces thrombin via activation of its inactive precursor prothrombin (FII) on the surface of phospholipid membranes. However, pathways and mechanisms of prothrombinase formation and substrate delivery are still discussed. Here we designed a novel mathematical model that considered different potential pathways of FXa or FII binding (from the membrane or from solution) and analyzed the kinetics of thrombin formation in the presence of a wide range of reactants concentrations. We observed the inhibitory effect of large FVa concentrations and this effect was phospholipid concentration-dependent. We predicted that efficient FII activation occurred via formation of the ternary complex, in which FVa, FXa and FII were in the membrane-bound state. Prothrombin delivery was mostly membrane-dependent, but delivery from solution was predominant under conditions of phospholipid deficiency or FXa/FVa excess. Likewise, FXa delivery from solution was predominant in the case of FVa excess, but high FII did not switch the FXa delivery to the solution-dependent one. Additionally, the FXa delivery pathway did not depend on the phospholipid concentration, being the membrane-dependent one even in case of the phospholipid deficiency. These results suggest a flexible mechanism of prothrombinase functioning which utilizes different complex formation and even inhibitory mechanisms depending on conditions.

C2-domain abscisic acid-related proteins regulate the dynamics of a plasma membrane H+-ATPase in response to alkali stress.

Arabidopsis (Arabidopsis thaliana) H+-ATPase1 (AHA1), a plasma membrane (PM)-localized H+-ATPase, plays a key role in plant alkali stress tolerance by pumping protons from the cytoplasm to the apoplast. However, its molecular dynamics are poorly understood. We report that many C2-domain ABA-related (CAR) protein family members interact with AHA1 in Arabidopsis. Single or double mutants of CAR1, CAR6, and CAR10 had no obvious phenotype of alkali stress tolerance, while their triple mutants showed significantly higher tolerance to this stress. The disruption of AHA1 largely compromised the increased alkali stress tolerance of the car1car6car10 mutant, revealing a key role of CARs in AHA1 regulation during the plant's response to a high alkali pH. Furthermore, variable angle total internal reflection fluorescence microscopy was used to observe AHA1-mGFP5 in intact Arabidopsis seedlings, revealing the presence of heterogeneous diffusion coefficients and oligomerization states in the AHA1 spots. In the aha1 complementation lines, alkali stress curtailed the residence time of AHA1 at the PM and increased the diffusion coefficient and particle velocity of AHA1. In contrast, the absence of CAR proteins decreased the restriction of the dynamic behavior of AHA1. Our results suggest that CARs play a negative role in plant alkali stress tolerance by interacting with AHA1 and provide a perspective to investigate the regulatory mechanism of PM H+-ATPase activity at the single-particle level.

COVID-19 infection triggered idiopathic capillary leak syndrome treated with ECMELLA.

Background: Idiopathic systemic capillary leak syndrome (ISCLS) is characterized by recurrent systemic capillary leakage and hypovolemic shock. Case presentation: We report a 59-year-old Caucasian man with ISCLS and persistent hypovolemic and cardiogenic shock after COVID-19 infection. Mechanical circulatory support was provided with veno-arterial extracorporeal membrane oxygenation and a microaxial pump. Massive fluid resuscitation was needed. Subsequent complications prolonged the intensive care treatment. Mechanical circulatory support was needed for 22 days. Cardiac function eventually fully recovered, and the patient survived without neurologic compromise. Conclusions: This case of severe ISCLS triggered by COVID-19 highlights that even the most severe hypovolemic and cardiogenic shock may be reversible in ISCLS.

Enhancing reading speed: the reading acceleration effect in Italian adult readers.

Introduction: Enhancing reading efficiency is of paramount importance in various academic, professional and clinical domains. Previous research, mostly from a single laboratory, has shown that externally imposed time constraints by means of text fading can enhance reading fluency in children and adults with varying reading abilities and in different languages. Methods: In the present study, we aimed at replicating and extending previous results in Italian readers. Three experiments (N = 90) were conducted: (i) to investigate the effects of continuous fading compared to character-wise fading, (ii) to investigate the influence of enlarged inter-letter spacing on reading acceleration outcomes, and (iii) to probe whether reading gains can be reliably observed off-line (after the acceleration) by comparing accelerated reading with an analog non-accelerated procedure. Results: Overall, results corroborate previous findings revealing that participants read 40% faster during the reading acceleration procedure, while maintaining the same accuracy levels. Continuous fading proved to be more effective than character-wise fading in enhancing reading speed, while larger inter-letter spacing did not significantly affect the reading speed gain. Albeit the non-clinical nature of our sample and its numerosity circumscribe the potential generalization, taking into account individual differences in the initial reading time, data suggests that reading acceleration leads to larger off-line speed increments with respect to non-accelerated reading. Discussion: Taken together, these findings offer valuable insights for the future application of reading acceleration procedures as part of multisession training programs for improving reading proficiency in a diverse range of clinical and non-clinical populations.

Comparing CHA2DS2-VA and CHA2DS2-VASc scores for stroke risk stratification in patients with atrial fibrillation: a temporal trends analysis from the retrospective Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) cohort.

Background: Contemporary data have shown a decrease in the ischaemic stroke risk associated with female sex in patients with atrial fibrillation (AF). We evaluated temporal trends in the predictive value of a non-sex CHA2DS2-VASc risk score (ie. CHA2DS2-VA). Methods: The FinACAF study covers all patients with incident AF between 2007 and 2018 in Finland from all levels of care. The CHA2DS2-VA score was compared with the CHA2DS2-VASc using continuous and category-based net reclassification indices (NRIs), integrated discrimination improvement (IDI), c-statistics and decision curve analyses. Findings: We identified 144,879 anticoagulant naïve patients with new-onset AF between 2007 and 2018 (49.9% women; mean age 72.1 years), of whom 3936 (2.7%) experienced ischaemic stroke during one-year follow-up. Based on both continuous and category-based NRIs, the CHA2DS2-VA score was inferior to the CHA2DS2-VASc in the early years (-0.333 (95% CI -0.411 to -0.261) and -0.118 (95% CI -0.137 to -0.099), respectively). However, the differences attenuated over time, and by the end of the study period, the continuous NRI became non-significant (-0.093 (95% CI -0.165 to 0.032)), whereas the category-based NRI reversed in favor of the CHA2DS2-VA (0.070 (95% CI 0.048-0.087)). The IDI was non-significant in early years (0.0009 (95% CI -0.0024 to 0.0037)), but over time became statistically significant in favor of the CHA2DS2-VA score (0.0022 (95% CI 0.0001-0.0044)). The Cox models fitted with the CHA2DS2-VA and the CHA2DS2-VASc scores exhibited comparable discriminative capability in the beginning of the study (p-value 0.63), but over time marginal differences in favor of the CHA2DS2-VA score emerged (p-value 0.0002). Interpretation: In 2007-2008 (when females had higher AF-related stroke risks than males), the CHA2DS2-VASc score outperformed the CHA2DS2-VA score, but the initial differences between the scores attenuated over time. By the end of the study period in 2017-2018 (with limited/no sex differences in AF-related stroke), there was marginal superiority for the CHA2DS2-VA score. Funding: This work was supported by the Aarne Koskelo Foundation, The Finnish Foundation for Cardiovascular Research, The Finnish State Research funding, and Helsinki and Uusimaa Hospital District research fund.

The association between serum vitamin A concentrations and virus hepatitis among U.S. adults from the NHANES database: a cross-sectional study.

Objective: According to the present study, the relationship between vitamin A (VA) levels and hepatitis virus carriage has been unclear and controversial. This study aimed to determine the potential relationship between serum VA levels and viral hepatitis and to provide ideas for future clinical treatments. Methods: A cross-sectional study was performed using the 2005-2006 and 2017-2018 National Health and Nutrition Examination Survey (NHANES) datasets. Multiple linear regression and logistic regression were adopted to analyze the association between serological hepatitis B surface antigen (HBsAg) or hepatitis C RNA (HCV-RNA) positivity and VA levels. There were 5,351 HBsAg-related responders and 242 HCV-RNA-related responders, including 52 HBsAg (+) and 104 HCV-RNA (+) responders. Results: Compared with HBsAg (-) and HCV-RNA (-) respondents, HBsAg (+) and HCV-RNA (+) respondents tended to have lower serum VA levels, respectively [1.63 (1.33 ~ 2.01) vs. 1.92 (1.57 ~ 2.34), P < 0.001; 1.54 (1.25 ~ 1.83) vs. 1.78 (1.46 ~ 2.26), P < 0.001]. A greater percentage of responders in the subclinical VA deficiency (SVAD) group were HBsAg (+) and HCV-RNA (+) than were those in the normal VA (VAN) group [2.4% (9/374) vs. 0.9% (43/4977), p = 0.003; 61.5% (16/26) vs. 40.7% (88/215), p = 0.043]. According to the results of the multiple regression analyses of the different models, the serum VA concentration was negatively correlated with HBsAg (+) and HCV-RNA (+) status (ß = -0.14, 95% CI = -0.30 to -0.01, p = 0.066; ß = -0.29, 95% CI = -0.50 ~ -0.09, p = 0.005, respectively). Compared to those with SVAD, patients with VAN were less likely to be serologically HBsAg (+) or HCV-RNA (+) (OR = 0.53, 95% CI = 0.25 ~ 1.10, p = 0.089; OR = 0.39, 95% CI = 0.18 ~ 0.84, p = 0.016, respectively). Conclusion: Our study provides evidence that patients who are HBsAg (+) or HCV-RNA (+) have a high incidence of SVAD. Moreover, HBsAg and HCV-RNA positivity are negatively correlated with VA levels, and patients with SVAD are more likely to carry HBsAg (+) or HCV-RNA (+). These findings suggest that the relationship between hepatitis viruses and vitamin A needs to be validated by more basic studies and clinical large-sample randomized controlled trials to provide ideas for new therapeutic targets.

Extracorporeal membrane oxygenation combined with hemoperfusion to assist in the rescue of aconitine poisoning: A case report.

Extracorporeal membrane oxygenation (ECMO) has been widely used as a clinical bridge for cardiopulmonary failure. We recently used combined veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and haemoperfusion to successfully treat a patient with acute aconitine poisoning. The patient was admitted to the Emergency Intensive Care Unit (EICU) in a state of coma and shock. Her received comprehensive treatment, including haemoperfusion and anti-shock therapy. 40 minutes after admission, the patient experienced sudden respiratory and cardiac arrest. After conventional defibrillation and cardiopulmonary resuscitation proved ineffective, veno-arterial ECMO was immediately initiated. One hour after initiation of VA-ECMO, the patient's heart rhythm stabilised to sinus rhythm. After 33 h of supportive care, the patient was awake, haemodynamically stable and the VA-ECMO was successfully removed. The patient made full recovery 7 days after admission.

Acute Vascular Complications of VA-ECMO in COVID-19 Patients. Does COVID-19 Affect the Outcome?

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) through the femoral artery and vein can lead to significant vascular complications. We retrospectively studied the acute vascular complications of Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) in COVID-19 patients compared to non-COVID patients during the period from January 2020 to July 2023. RESULTS: Seventy-eight patients underwent VA-ECMO for various indications from January 2020 to July 2023. The studied patients had a mean age of 59.6 ± 6.9 years for non-COVID patients (38 patients), and 62.2 ± 7.6 years for COVID patients (40 patients), with a P = 0.268. In non-COVID patients, The baseline characteristics were similar in both groups. The primary indications for ECMO were cardiac diseases, followed by respiratory failure (78.9% vs 10.5%). Conversely, in COVID patients, respiratory failure due to COVID-19 infection was the main indication (45% vs 40%). The overall incidence of general complications, including cerebrovascular stroke, acute kidney injury, intracardiac thrombi, and wound infection, was comparable in both groups (31.6% vs 45%). The overall incidence of vascular complications in both groups was 33.3%. Ipsilateral acute lower limb ischemia occurred in 5.3% vs 10% of non-COVID and COVID patients, respectively. Thrombosis of the distal perfusion catheter (DPC) occurred in 10.5% vs 15%, respectively. CONCLUSION: During the COVID-19 pandemic, an increasing number of patients required VA-ECMO due to associated respiratory failure. Patients undergoing VA-ECMO are at high risk of developing various vascular complications. COVID-19 significantly increases the risk of acute limb ischemia and distal perfusion catheter thrombosis in both upper and lower limbs. However, other VA-ECMO-related vascular complications are comparable between COVID-19 and non-COVID patients.

Limonin (LM) and its derivatives: Unveiling the neuroprotective and anti-inflammatory potential of LM and V-A-4 in the management of Alzheimer's disease and Parkinson's disease.

Neuroinflammation and neuronal apoptosis are central pathogenic consequences associated with Alzheimer's Disease (AD) and Parkinson's Disease (PD). Limonin (LM), a tetracyclic triterpenoid available in citrus fruits, has anti-tumor, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective actions. LM derivative, V-A-4 emerged as a potential neuroprotective drug due to their ability to target multiple molecular pathways intertwined with neuroinflammation and neuronal apoptosis. To date, the treatment of AD and PD is not successful even though the understanding of the mechanism of neuroinflammation and neuronal apoptosis is vast in the literature. Thus, there is an urgent need to identify novel neuroprotective drugs that could target the multiple molecular pathways associated with neuroinflammation and neuronal apoptosis. The various online databases (Google scholar, Pubmed, Scopus) were searched via keywords: limonin, limonin derivatives and neuroprotection. This review highlights the multifunctional nature of LM and derivatives in combating neuroinflammation and neuronal apoptosis by stimulating PI3K/AKT and downregulating TLR4/NF-κB critical pathways. By intervening in the secretion of NO and TNF-α from glial cells, V-A-4 attenuates the damaging cascade of neuroinflammation by suppressing IKK-α and IKK-ß. Furthermore, V-A-4 demonstrates its versatility by suppressing the manifestation of miR-146a and miR-155, both intimately linked to neuroinflammation, this review summarized the activities of LM and its derivatives against AD and PD, with a special focus on V-A-4 as an effective neuroprotective drug. V-A-4's ability to stimulate PI3K/AKT signaling further underscores its neuroprotective effect in combating AD and PD. More in-vitro cell line studies are needed to develop V-A-4 as an upcoming neuroprotective compound.

A training programme for novice extracorporeal resuscitation providers.

Introduction: The use of extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest is increasing globally. However, providing equity of access to all patients is challenging, and to date, access has been limited to inner city areas surrounding major hospitals. To increase the availability of ECPR in our jurisdiction, we sought to train pre-hospital physicians with no experience in extracorporeal membrane oxygenation cardiopulmonary resuscitation (ECPR). To enable this, we sort to develop and teach a syllabus that would provide novice ECPR providers the skill to perform ECPR safely and effectively in the pre-hospital environment. Methods: This training programme consisted of 11 pre-hospital physicians and six critical care paramedics. All participants had no prior hospital experience instituting or managing ECPR patients. The training programme was multimodal utilising a porcine model of heart failure to teach time pressured dynamic physiological troubleshooting, cadaver labs to teach cannulation, didactic teaching and simulation. Key knowledge and skill domains were identified. Each learning framework was built upon with a final focus on integrating all skill domains required to successfully initiate ECPR. Results: The training program was completed from February 2022 to August 2023. Knowledge progression was assessed at key stages via written and practical examination. Each participant demonstrated clear knowledge and skill progression at the key stages of the training programme. At the end of the training programme, participants met the pre-defined standards to progress to ECPR provision in the pre-hospital environment. Conclusion: We present a training program for novice ECPR providers performing ECPR in the pre-hospital setting. The outcomes of this training program can provide a training framework for both novices, low volume ECMO centres and pre-hospital clinicians.