Influence of perfusate on liver viability during hypothermic machine perfusion

AIM: To optimize the perfusates used for hypothermicmachine perfusion(HMP).METHODS: Sprague-Dawley rats were assigned randomly to three groups(n = 12 per group) that received either saline, University of Wisconsin coldstorage solution(UW) or histidine-tryptophan-ketoglutarate solution(HTK) as the perfusate. Each group was divided into two subgroups: static cold storage(SCS) and HMP(n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate(0-4?℃) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase(AST), alanine transaminase(ALT) and lactate dehydrogenase(LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight(D/W) ratio, and malondialdehyde(MDA) and adenosine-triphosphate(ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups.RESULTS: Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period(SCS vs HMP using saline: ALT3, 225.00 ± 105.62 vs 49.50 ± 18.50, P = 0.047; LDH3, 1362.17 ± 563.30 vs 325.75 ± 147.43, P = 0.041; UW: LDH6, 2880.14 ± 948.46 vs 2135.00 ± 174.27, P = 0.049; HTK, AST6, 307.50 ± 52.95 vs 185.20 ± 20.46, P = 0.041); HMP decreased MDA level(saline, 2.79 ± 0.30 vs 1.09 ± 0.09, P = 0.008; UW, 3.01 ± 0.77 vs 1.23 ± 0.68, P = 0.005; HTK, 3.30 ± 0.52 vs 1.56 ± 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline(vs saline, 3.41 ± 0.49 vs 5.00 ± 0.38, P < 0.001; vs UW, 3.41 ± 0.49 vs 4.52 ± 0.63, P = 0.007); UW reduced edema most efficiently(vs saline, 0.68 ± 0.02 vs 0.79 ± 0.05, P = 0.013), while HTK maintained ATP levels best(vs saline, 622.60 ± 29.11 vs 327.43 ± 44.66, P < 0.001; vs UW, 622.60 ± 29.11 vs 301.80 ± 37.68, P < 0.001).CONCLUSION: HMP is superior to SCS in maintaining both architecture and function of liver grafts. Further, HTK was found to be the optimal perfusate for HMP.

Medin synergized with vascular amyloid-beta deposits accelerates cognitive decline in Alzheimer's disease:a potential biomarker

Brain vascular dysfunction in Alzheimer s disease(AD) pathogenesis has become increasingly clea r.Accumulating evidence shows that damaged vascular,including large or small vessels and even neurovascular unit,may accelerate the neuropathological process of AD via disrupting brain hypoperfusion,aberrant angiogenesis,and neuroinflammatory response,etc.Thus,vascular dysfunction makes a substantially contribution to the cognitive decline of AD patients.

Predicting major adverse cardiovascular events after orthotopic liver transplantation using a supervised machine learning model:A cohort study

BACKGROUND Liver transplant(LT)patients have become older and sicker.The rate of post-LT major adverse cardiovascular events(MACE)has increased,and this in turn raises 30-d post-LT mortality.Noninvasive cardiac stress testing loses accuracy when applied to pre-LT cirrhotic patients.AIM To assess the feasibility and accuracy of a machine learning model used to predict post-LT MACE in a regional cohort.METHODS This retrospective cohort study involved 575 LT patients from a Southern Brazilian academic center.We developed a predictive model for post-LT MACE(defined as a composite outcome of stroke,new-onset heart failure,severe arrhythmia,and myocardial infarction)using the extreme gradient boosting(XGBoost)machine learning model.We addressed missing data(below 20%)for relevant variables using the k-nearest neighbor imputation method,calculating the mean from the ten nearest neighbors for each case.The modeling dataset included 83 features,encompassing patient and laboratory data,cirrhosis complications,and pre-LT cardiac assessments.Model performance was assessed using the area under the receiver operating characteristic curve(AUROC).We also employed Shapley additive explanations(SHAP)to interpret feature impacts.The dataset was split into training(75%)and testing(25%)sets.Calibration was evaluated using the Brier score.We followed Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for reporting.Scikit-learn and SHAP in Python 3 were used for all analyses.The supplementary material includes code for model development and a user-friendly online MACE prediction calculator.RESULTS Of the 537 included patients,23(4.46%)developed in-hospital MACE,with a mean age at transplantation of 52.9 years.The majority,66.1%,were male.The XGBoost model achieved an impressive AUROC of 0.89 during the training stage.This model exhibited accuracy,precision,recall,and F1-score values of 0.84,0.85,0.80,and 0.79,respectively.Calibration,as assessed by the Brier score,indicated excellent model calibration with a score of 0.07.Furthermore,SHAP values highlighted the significance of certain variables in predicting postoperative MACE,with negative noninvasive cardiac stress testing,use of nonselective beta-blockers,direct bilirubin levels,blood type O,and dynamic alterations on myocardial perfusion scintigraphy being the most influential factors at the cohort-wide level.These results highlight the predictive capability of our XGBoost model in assessing the risk of post-LT MACE,making it a valuable tool for clinical practice.CONCLUSION Our study successfully assessed the feasibility and accuracy of the XGBoost machine learning model in predicting post-LT MACE,using both cardiovascular and hepatic variables.The model demonstrated impressive performance,aligning with literature findings,and exhibited excellent calibration.Notably,our cautious approach to prevent overfitting and data leakage suggests the stability of results when applied to prospective data,reinforcing the model’s value as a reliable tool for predicting post-LT MACE in clinical practice.

Predictive value of hypothermic machine perfusion parameters combined perfusate biomarkers in deceased donor kidney transplantation

Background:Delayed graft function(DGF)is the main cause of renal function failure after kidney transplantation.This study aims at investigating the value of hypothermic machine perfusion(HMP)parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor(DD)kidney transplantation.Methods:HMP parameters,perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1,2019 to August 31,2019 in the First Affiliated Hospital of Xi’an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis.Results:In this study,the DGF incidence was 17.7%(20/113);The multivariate logistic regression results showed that terminal resistance(OR:1.879,95%CI 1.145-3.56)and glutathione S-transferase(GST)(OR=1.62,95%CI 1.23-2.46)were risk factors for DGF;The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time(HR=0.823,95%CI 0.735-0.981).The model combining terminal resistance and GST(AUC=0.888,95%CI:0.842-0.933)significantly improved the DGF predictability compared with the use of terminal resistance(AUC=0.756,95%CI 0.693-0.818)or GST alone(AUC=0.729,95%CI 0.591-0.806).Conclusion:According to the factors analyzed in this study,the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.

Relationship between the analgesic effect of electroacupuncture and CCK-8 content in spinal perfusate in rats

There exists significant individual variation in electroacupuncture (EA) induced analgesia.Rats may be classified as high- and low-responders according to their response to EA analgesia. The content of cholecystokinin octapeptide like immunoreactivity (CCK-8-ir) in the spinal perfusate of highresponder (HR) and low-responder (LR) rats was measured with radioimmunoassay. The result showed that the CCK-8-ir content in LR rats was significantly lower than that in HR rats. There exists a negative correlation between the EA effect and the CCK-8-ir content during EA stimulation. It is concluded that the spinal release of CCK-8 may be one of the key factors determining the effect of EA analgesia.

Routine utilization of machine perfusion in liver transplantation:Ready for prime time?

The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ preservation.This editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.

Hemoperfusion and continuous veno-venous hemodiafiltration for eliminating chlorfenapyr in poisoning patients

Chlorfenapyr is a liposoluble insecticide belonging to the pyrrole family.Chlorfenapyr is activated when the N-ethoxymethyl side chain breaks,forming a toxic metabolite,which uncouples oxidative phosphorylation in the mitochondria,inhibits the production of adenosine triphosphate (ATP),and leads to the death of cells and targe organisms.[1] Symptoms of chlorfenapyr poisoning in patients are mild and atypical in the early stage,especially in patients receiving low dose exposure;however,such cases are rare and may be ignored by physicians,often leading to delayed treatment.[2,3].

Early peripheral perfusion index predicts 28-day outcome in patients with septic shock

BACKGROUND:To investigate the prognostic value of the peripheral perfusion index(PPI)in patients with septic shock.METHODS:This prospective cohort study,conducted at the emergency intensive care unit of Peking University People's Hospital,recruited 200 patients with septic shock between January 2023 and August 2023.These patients were divided into survival(n=84)and death(n=116)groups based on 28-day outcomes.Clinical evaluations included laboratory tests and clinical scores,with lactate and PPI values assessed upon admission to the emergency room and at 6 h and 12 h after admission.Risk factors associated with mortality were analyzed using univariate and multivariate Cox regression analyses.Receiver operator characteristic(ROC)curve was used to assess predictive performance.Mortality rates were compared,and Kaplan-Meier survival plots were created.RESULTS:Compared to the survival group,patients in the death group were older and had more severe liver damage and coagulation dysfunction,necessitating higher norepinephrine doses and increased fl uid replacement.Higher lactate levels and lower PPI levels at 0 h,6 h,and 12 h were observed in the death group.Multivariate Cox regression identifi ed prolonged prothrombin time(PT),decreased 6-h PPI and 12-h PPI as independent risk factors for death.The area under the curves for 6-h PPI and 12-h PPI were 0.802(95%CI 0.742-0.863,P<0.001)and 0.945(95%CI 0.915-0.974,P<0.001),respectively,which were superior to Glasgow Coma Scale(GCS),Sequential Organ Failure Assessment(SOFA)scores(0.864 and 0.928).Cumulative mortality in the low PPI groups at 6 h and 12 h was signifi cantly higher than in the high PPI groups(6-h PPI:77.52%vs.22.54%;12-h PPI:92.04%vs.13.79%,P<0.001).CONCLUSION:PPI may have value in predicting 28-day mortality in patients with septic shock.

Bioelectronic medicine in modulation of cortical spreading depolarization and beyond

Bioelectronic interventions,specifically trigeminal nerve st imulat ion(TNS),have attracted considerable attention in conditions where cortical spreading depolarizations(CSDs)accompanied by compromised cerebral perfusion may exacerbate neurological damage.While pharmacological interventions have demonstrated initial potential in addressing CSDs,a standardized treatment approach has not yet been established.The objective of this perspective is to explore emerging bioelectronic methodologies for addressing CSDs,particularly emphasizing TNS,and to underscore TNS’s capacity to enhance neurovascular coupling and cerebral perfusion.

New strategy for distal limb perfusion in veno-arterial extracorporeal membrane oxygenation treatment: application of continuous renal replacement therapy tubing

Extracorporeal membrane oxygenation(ECMO)is a technology that can temporarily take over the functions of the heart and lungs.Acute kidney injury is a common issue in patients receiving ECMO treatment,with reported incidence rates ranging from 70%to 85%.[1]To maintain the balance of fluids and electrolytes in patients,continuous renal replacement therapy(CRRT)is frequently employed.

“机械灌注+”应用于扩大标准供肝移植--肝尽其用

Transplantation represents the most effective treatment for end-stage liver diseases but is limited by the shortage of healthy donor organs.Extended criteria donor(ECD)liver grafts are increasingly utilized in clinical practice to mitigate this challenge.However,impaired ischemic tolerance of these grafts jeopardizes organ viability during cold storage.Machine perfusion(MP)was designed to improve organ preservation and reduce posttransplant complications.Nevertheless,it is increasingly evident that MP alone may not preserve ECD grafts optimally.Increasing emphasis has thus been placed on modified MP strategies,including the use of different perfusates,modified perfusion modalities,and different therapeutic interventions.Here,we introduce a novel term,"MP Plus,"denoting these additional strategies that are designed to restore organ function and potentially enable regeneration of ECD grafts.In this review,we summarize the existing and potential modified MP strategies and discuss their advantages in reconditioning different ECD grafts in clinical settings.

Adipose-derived mesenchymal stem cell-incorporated PLLA porous microspheres for cartilage regeneration

Background:In facial plastic surgery,patients with nasal deformity are often treated by rib cartilage transplantation.In recent years,cartilage tissue engineering has developed as an alternative to complex surgery for patients with minor nasal defects via injection of nasal filler material.In this study,we prepared an injectable nasal filler material containing poly-L-l actic acid(PLLA)porous microspheres(PMs),hyaluronic acid(HA)and adipose-derived mesenchymal stem cells(ADMSCs).Methods:We seeded ADMSCs into as-prepared PLLA PMs using our newly invented centrifugation perfusion technique.Then,HA was mixed with ADMSC-i ncorporated PLLA PMs to form a hydrophilic and injectable cell delivery system(ADMSCincorporated PMH).Results:We evaluated the biocompatibility of PMH in vitro and in vivo.PMH has good injectability and provides a favorable environment for the proliferation and chondrogenic differentiation of ADMSCs.In vivo experiments,we observed that PMH has good biocompatibility and cartilage regeneration ability.Conclusion:In this study,a injectable cell delivery system was successfully constructed.We believe that PMH has potential application in cartilage tissue engineering,especially in nasal cartilage regeneration.

Cerebral pseudoinfarction due to venoarterial extracorporeal membrane oxygenation:A case report

BACKGROUND Neurological complications are common in the management of venoarterial extracorporeal membrane oxygenation(VA-ECMO),with most patients requiring sedation and intubation,limiting the assessment of neurological function.Therefore,we must rely on advanced neuroimaging techniques,such as computed tomography angiography(CTA)and computed tomography perfusion(CTP).Because ECMO changes the normal blood flow pattern,it may interfere with the contrast medium in some special cases,leading to artifacts and ultimately misleading clinical decisions.CASE SUMMARY A 61-year-old man presented to a local hospital with chest tightness and pain 1 d prior to presentation.The patient was treated with VA-ECMO after sudden cardiac and respiratory arrest at a local hospital.For further treatment,the patient was transferred to our hospital.The initial consciousness assessment was not clear,and routine CTP was performed to understand the intracranial changes,which suggested a large area of cerebral infarction on the right side;however,the cerebral oxygen was not consistent with the CTP results,and the reexamination of CTA still suggested a right cerebral infarction.To identify this difference,bedside transcranial Doppler was performed,and the blood flow on both sides was different.By reducing the ECMO flow,CTP reexamination showed that the results were normal and consistent with the clinical results.On day 3,the patient was alert and showed good limb movements.CONCLUSION In patients with peripheral VA-ECMO,cerebral perfusion confirmed by CTP and CTA may lead to false cerebral infarction.

Gut microbiota-derived short-chain fatty acids and depression:deep insight into biological mechanisms and potential

The gut microbiota is a complex and dynamic ecosystem known as the second brain'.Composing the microbiota-gut-brain axis,the gut microbiota and its metabolites regulate the central nervous system through neural,endocrine and immune pathways to ensure the normal functioning of the organism,tuning individuals'health and disease status.Short-chain fatty acids(SCFAs),the main bioactive metabolites of the gut microbiota,are involved in several neuropsychiatric disorders,including depression.SCFAs have essential effects on each component of the microbiota-gut-brain axis in depression.In the present review,the roles of major SCFAs(acetate,propionate and butyrate)in the pathophysiology of depression are summarised with respect to chronic cerebral hypoperfusion,neuroinflammation,host epigenome and neuroendocrine alterations.Concluding remarks on the biological mechanisms related to gut microbiota will hopefully address the clinical value of microbiota-related treatments for depression.

The potential mechanism and clinical application value of remote ischemic conditioning in stroke

Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.

Portal vein pulsatility:An important sonographic tool assessment of systemic congestion for critical ill patients

In this editorial we comment on the article by Kuwahara et al,published in the recent issue of the World Journal of Cardiology.In this interesting paper,the authors showed a correlation between portal vein pulsatility ratio,examined by bedside ultrasonography,and prognosis of hospitalized patients with acute heart failure.Systemic congestion is being notoriously underdetected in the acutely ill population with conventional methods like clinical examination,biomarkers,central venous pressure estimation and X-rays.However,congestion should be a key therapeutic target due to its deleterious effects to end organ function and subsequently patient prognosis.Doppler flow assessment of the abdominal veins is gaining popularity worldwide,as a valuable tool in estimating comprehensively congestion and giving a further insight into hemodynamics and patient management.

Unveiling the silent link:Normal-tension glaucoma's enigmatic bond with cardiac blood flow

This comprehensive review embarks on a captivating journey into the complex relationship between cardiology and normal-tension glaucoma(NTG),a condition that continues to baffle clinicians and researchers alike.NTG,characterized by optic nerve damage and visual field loss despite normal intraocular pressure,has long puzzled clinicians.One emerging perspective suggests that alterations in ocular blood flow,particularly within the optic nerve head,may play a pivotal role in its pathogenesis.While NTG shares commonalities with its high-tension counterpart,its unique pathogenesis and potential ties to cardiovascular health make it a fascinating subject of exploration.It navigates through the complex web of vascular dysregulation,blood pressure and perfusion pressure,neurovascular coupling,and oxidative stress,seeking to uncover the hidden threads that tie the heart and eyes together in NTG.This review explores into the intricate mechanisms connecting cardiovascular factors to NTG,shedding light on how cardiac dynamics can influence ocular health,particularly in cases where intraocular pressure remains within the normal range.NTG's enigmatic nature,often characterized by seemingly contradictory risk factors and clinical profiles,underscores the need for a holistic approach to patient care.Drawing parallels to cardiac health,we examine into the shared vascular terrain connecting the heart and the eyes.Cardiovascular factors,including systemic blood flow,endothelial dysfunction,and microcirculatory anomalies,may exert a profound influence on ocular perfusion,impacting the delicate balance within the optic nerve head.By elucidating the subtle clues and potential associations between cardiology and NTG,this review invites clinicians to consider a broader perspective in their evaluation and management of this elusive condition.As the understanding of these connections evolves,so too may the prospects for early diagnosis and tailored interventions,ultimately enhancing the quality of life for those living with NTG.

Clinical approach for pulmonary lymphatic disorders

In this editorial,we discuss the clinical implications of the article“Lymphatic plastic bronchitis and primary chylothorax:A study based on computed tomography lymphangiography”published by Li et al.Pulmonary lymphatic disorders involve abnormalities in the lymphatic tissues within the thoracic cavity.Specifically,pulmonary lymphatic perfusion syndrome describes a condition where the flow of lymphatic fluid in the lungs is redirected towards abnormally widened lymphatic vessels.Clinically,individuals with this syn-drome may experience symptoms such as chyloptysis,plastic bronchitis(PB),chylothorax,chylopericardium,and interstitial lung disease.These disorders can be caused by various factors,including PB,chylothorax,and complex lymphatic malformations.Advancements in lymphatic imaging techniques,such as in-tranodal lymphangiography,computed tomography lymphangiography,and dynamic contrast-enhanced magnetic resonance lymphangiography,have enabled the detection of abnormal lymphatic flow.This has enhanced our understanding of the pathophysiology of these conditions.Additionally,innovative minimally invasive treatments,such as thoracic duct embolization,selective embolization of lymphatic channels,and surgical procedures aim to improve clinical condition of patients and address their dietary needs.

Effect of bivalirudin on myocardial microcirculation and adverse events after interventional therapy in older patients with acute coronary syndrome

BACKGROUND Bivalirudin,a direct thrombin inhibitor,is used in anticoagulation therapies as a substitute for heparin,especially during cardiovascular procedures such as percutaneous coronary intervention.AIM To explore the effect of bivalirudin on myocardial microcirculation following an intervention and its influence on adverse cardiac events in elderly patients with acute coronary syndrome(ACS).METHODS In total,165 patients diagnosed with acute myocardial at our hospital between June 2020 and June 2022 were enrolled in this study.From June 2020 to June 2022,elderly patients with ACS with complete data were selected and treated with interventional therapy.The study cohort was randomly divided into a study group(n=80,administered bivalirudin)and a control group(n=85,administered unfractionated heparin).Over a 6-mo follow-up period,differences in emergency processing times,including coronary intervention,cardiac function indicators,occurrence of cardiovascular events,and recurrence rates,were analyzed.RESULTS Significant differences were observed between the study cohorts,with the observation group showing shorter emergency process times across all stages:Emergency classification;diagnostic testing;implementation of coronary intervention;and conclusion of emergency treatment(P<0.05).Furthermore,the left ventricular ejection fraction in the observation group was significantly higher(P<0.05),and the creatine kinase-MB and New York Heart Association scores were CONCLUSION In elderly patients receiving interventional therapy for ACS,bivalirudin administration led to increased activated clotting time achievement rates,enhanced myocardial reperfusion,and reduced incidence of bleeding complications and adverse cardiac events.

Cold ischemia time in liver transplantation:An overview

The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its reperfusion in the recipient is defined as cold ischemia time(CIT).This simple definition reveals a multifactorial time frame that depends on donor hepatectomy time,transit time,and recipient surgery time,and is one of the most important donor-related risk factors which may influence the graft and recipient’s survival.Recently,the growing demand for the use of marginal liver grafts has prompted scientific exploration to analyze ischemia time factors and develop different organ preservation strategies.This review details the CIT definition and analyzes its different factors.It also explores the most recent strategies developed to implement each timestamp of CIT and to protect the graft from ischemic injury.