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].

Machine perfusion and the prevention of ischemic type biliary lesions following liver transplant:What is the evidence?

The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.

Correlation between Automated Quantification of Lung Perfusion Blood Volume (PBV) and Pulmonary Artery Pressure

Purpose: Dual-energy CT (DECT) can be used for quantification of lung perfusion blood volume (PBV), allowing objective evaluation. However, no reports have investigated pulmonary perfusion correlating with pulmonary artery pressure (PAP) in patients with chronic pulmonary diseases. The purpose was to evaluate automated quantification of the lung PBV using dual-energy CT, and its correlation with PAP. Methods: 274 patients who underwent echocardiography within two weeks also underwent CT. The population was divided into high (&ge;40 mmHg) and low (<40 mmHg) estimated systolic PAP (sPAP) groups (n = 63 and n = 211, respectively). We retrospectively eva-luated the lung PBV using Syngo software, and correlations between the lung PBV and estimated sPAP. Results: Lung PBV values were 25.0 ± 9.6 and 29.0 ± 9.3 Hounsfield units (HU) in high and low sPAP groups, respectively, with a significant difference between them (p = 0.003). In the high sPAP group with underlying lung diseases (n = 15), chronic thromboembolism (n = 25), pulmonary artery stenosis (n = 12), and left heart failure (n = 11), using the Dana Point classification system, lung PBV values were 18.6 ± 1.6, 25.1 ± 4.5, 25.8 ± 4.5, and 32.7 ± 9.4 HU, respectively. There were significant differences in quantification of the lung PBV among them. The mean sPAP of subjects with left heart failure was significantly higher than in the others. In subjects with left heart failure, a positive correlation between the lung PBV value and sPAP was noted (R = 0.721, p < 0.0001). Conclusions: Automated quantification of the lung PBV may estimate the high sPAP. The lung PBV may contribute to clarifying the etiology of a high PAP due to left heart failure.

Correlation of magnetic resonance signal characteristics and perfusion parameters assessed by volume perfusion computed tomography in hepatocellular carcinoma:Impact on lesion characterization

AIM: To find out if magnetic resonance(MR)-signal characteristics of hepatocellular carcinomas(HCC) correlate with perfusion parameters assessed by volume perfusion computed tomography(VPCT).METHODS: From October 2009 to January 2014, 26(mean age, 69.3 years) patients with 36 HCC lesions who underwent both VPCT and MR liver imaging were analysed. We compared signal intensity in the T1 wand T2w-images and wash-in/wash-out kinetics on postcontrast MR images with mean values of blood flow(BF, mL/100 mL per minute), blood volume(BV, mL/100 mL), k-trans(mL/100 mL per minute), arterial liver perfusion(mL/100 mL per minute), portal venous perfusion and hepatic perfusion index(HPI, %) obtained by VPCT. Signal intensity on magnetic resonance imaging(MRI) was classified hyper/iso/hypointense compared with surrounding liver parenchyma. RESULTS: Signal intensity on native T1w- and T2 wimages was hyper/iso/hypo in 4/16/16 and 21/14/1 lesions, respectively. Wash-in and wash-out contrast kinetics were found on MRI in 33 of 36 lesions(91.7%) and 25 of 36 lesions(69.4%), respectively. The latter was observed significantly more often in higher graded lesions(P < 0.005). HPI was 94.7% ± 6.5%. There was no significant relationship between lesion's MRsignal intensity, MR signal combinations, size and any of the VPCT-perfusion parameters. However HPI was constantly high in all HCC lesions.CONCLUSION: VPCT parameters add limited value to MR-lesion characterization. However in HCC lesions with atypical MR signal characteristics HPI can add a parameter to ensure HCC diagnosis.

In vivo solid phase microextraction for therapeutic monitoring and pharmacometabolomic fingerprinting of lung during in vivo lung perfusion of FOLFOX

In vivo lung perfusion(IVLP)is a novel isolated lung technique developed to enable the local,in situ administration of high-dose chemotherapy to treat metastatic lung cancer.Combination therapy using folinic acid(FOL),5-fluorouracil(F),and oxaliplatin(OX)(FOLFOX)is routinely employed to treat several types of solid tumours in various tissues.However,F is characterized by large interpatient variability with respect to plasma concentration,which necessitates close monitoring during treatments using of this compound.Since plasma drug concentrations often do not reflect tissue drug concentrations,it is essential to utilize sample-preparation methods specifically suited to monitoring drug levels in target organs.In this work,in vivo solid-phase microextraction(in vivo SPME)is proposed as an effective tool for quantitative therapeutic drug monitoring of FOLFOX in porcine lungs during pre-clinical IVLP and intravenous(IV)trials.The concomitant extraction of other endogenous and exogenous small molecules from the lung and their detection via liquid chromatography coupled to high resolution mass spectrometry(LC-HRMS)enabled an assessment of FOLFOX's impact on the metabolomic profile of the lung and revealed the metabolic pathways associated with the route of administration(IVLP vs.IV)and the therapy itself.This study also shows that the immediate instrumental analysis of metabolomic samples is ideal,as long-term storage at80℃ results in changes in the metabolite content in the sample extracts.

Whole-brain CT Perfusion at Admission and During Delayed Time-window Detects the Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage

Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage.Methods Eighty patients underwent CTP at admission and during DCITW.The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group,and comparisons were also made between admission and DCITW within each group.The qualitative color-coded perfusion maps were recorded.Finally,the relationship between CTP parameters and DCI was assessed by receiver operating characteristic(ROC)analyses.Results With the exception of cerebral blood volume(P=0.295,admission;P=0.682,DCITW),there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW.In the DCI group,the extreme parameters were significantly different between admission and DCITW.The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps.For the detection of DCI,mean transit time to the center of the impulse response function(Tmax)at admission and mean time to start(TTS)during DCITW had the largest area under curve(AUC),0.698 and 0.789,respectively.Conclusion Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW.The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.

Cardiovascular outcomes and mortality after abnormal myocardial perfusion scans in the elderly:a retrospective study at a tertiary care institution

While the diagnostic and prognostic utility of single photon emission computed tomography(SPECT)myocardial perfusion scan(MPS)has been well established,[1,2]there is a paucity of literature evaluating SPECT MPS in elderly populations.Specifically,it is unclear whether the prognostic value of MPS diminishes as patients get older.We conducted this study to evaluate the role of SPECT MPS in risk-stratifying a large sample of elderly patients with or without known coronary artery disease(CAD)and hypothesized that abnormal MPS in patients over 75 years would be associated with a greater risk of all-cause mortality and major adverse cardiac events.

Computed tomography perfusion in differentiating portal hypertension: A correlation study with hepatic venous pressure gradient

BACKGROUND Hepatic venous pressure gradient(HVPG)is the gold standard for diagnosis of portal hypertension(PH),invasiveness and potential risks in the process of measurement limited its widespread use.AIM To investigate the correlation of computed tomography(CT)perfusion parameters with HVPG in PH,and quantitatively assess the blood supply changes in liver and spleen parenchyma before and after transjugular intrahepatic portosystemic shunt(TIPS).METHODS Twenty-four PH related gastrointestinal bleeding patients were recruited in this study,and all patients were performed perfusion CT before and after TIPS surgery within 2 wk.Quantitative parameters of CT perfusion,including liver blood volume(LBV),liver blood flow(LBF),hepatic arterial fraction(HAF),spleen blood volume(SBV)and spleen blood flow(SBF),were measured and compared before and after TIPS,and the quantitative parameters between clinically significant PH(CSPH)and non-CSPH(NCSPH)group were also compared.Then the correlation of CT perfusion parameters with HVPG were analyzed,with statistical significance as P<0.05.RESULTS For all 24 PH patients after TIPS,CT perfusion parameters demonstrated decreased LBV, increased HAF, SBV and SBF, with no statistical difference in LBF. Compared withNCSPH, CSPH showed higher HAF, with no difference in other CT perfusion parameters. HAFbefore TIPS showed positive correlation with HVPG (r = 0.530, P = 0.008), while no correlation wasfound in other CT perfusion parameters with HVPG and Child-Pugh scores.CONCLUSIONHAF, an index of CT perfusion, was positive correlation with HVPG, and higher in CSPH thanNCSPH before TIPS. While increased HAF, SBF and SBV, and decreased LBV, were found afterTIPS, which accommodates a potential non-invasive imaging tool for evaluation of PH.

Intraoperative pancreas stump perfusion assessment during pancreaticoduodenectomy:A systematic scoping review

BACKGROUND Post-operative pancreatic fistula(POPF)is the primary cause of morbidity following pancreaticoduodenectomy.Rates of POPF have remained high despite well known risk factors.The theory that hypoperfusion of the pancreatic stump leads to anastomotic failure has recently gained interest.AIM To define the published literature with regards to intraoperative pancreas perfusion assessment and its correlation with POPF.METHODS A systematic search of available literature was performed in November 2022.Data extracted included study characteristics,method of assessment of pancreas stump perfusion,POPF and other post-pancreatic surgery specific complications.RESULTS Five eligible studies comprised two prospective non-randomised studies and three case reports,total 156 patients.Four studies used indocyanine green fluorescence angiography to assess the pancreatic stump,with the remaining study assessing pancreas perfusion by visual inspection of arterial bleeding of the pancreatic stump.There was significant heterogeneity in the definition of POPF.Studies had a combined POPF rate of 12%;intraoperative perfusion assessment revealed hypoperfusion was present in 39%of patients who developed POPF.The rate of POPF was 11%in patients with no evidence of hypoperfusion and 13%in those with evidence of hypoperfusion,suggesting that not all hypoperfusion gives rise to POPF and further analysis is required to analyse if there is a clinically relevant cut off.Significant variance in practice was seen in the pancreatic stump management once hypoperfusion was identified.CONCLUSION The current published evidence around pancreas perfusion during pancreaticoduodenectomy is of poor quality.It does not support a causative link between hypoperfusion and POPF.Further well-designed prospective studies are required to investigate this.

Effects of cytoreductive surgery combined with hyperthermic perfusion chemotherapy on prognosis of patients with advanced gallbladder cancer

BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatment outcomes,resulting in high mortality rates.The available treatment options for GC are relatively limited.One emerging treatment modality is hyperthermic intraperitoneal chemotherapy(HIPEC).HIPEC involves delivering heated chemotherapy directly into the abdominal cavity.It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions,aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity.AIM To determine the effects of cytoreductive surgery(CRS)combined with HIPEC on the short-term prognosis of patients with advanced GC.METHODS Data from 80 patients treated at the Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed.The control group comprised 44 patients treated with CRS,and the research group comprised 36 patients treated with CRS combined RESULTS The baseline data of the research and control groups were similar(P>0.05).Six days after surgery,the alanine aminotransferase,aspartate aminotransferase,total bilirubin,and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups(P<0.05).However,the values did not differ between the two groups six days postoperatively(P>0.05).Similarly,the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups(P<0.05),but they did not differ between the groups six days postoperatively(P>0.05).Furthermore,the research group had fewer postoperative adverse reactions than the control group(P=0.027).Finally,a multivariate Cox analysis identified the tumor stage,distant metastasis,and the treatment plan as independent factors affecting prognosis(P<0.05).The three-year survival rate in the study group was higher than that in the control group(P=0.002).CONCLUSION CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.

Progress of mechanical perfusion in split liver transplantation

Split liver transplantation is an essential means which expand the donor pool currently and the two livers obtained after splitting are marginal donor livers.The adoption of Static Cold Storage during allocation and preservation leads to a higher cold ischemia time,thus increasing the occurrence of related postoperative complications,which limits the further development of split-liver transplantation.Mechanical perfusion as a complement to split liver transplantation can minimize the damage to the marginal donor liver during preservation and reduce the occurrence of ischemia-reperfusion.At present,mechanical perfusion has achieved better efficacy in other types of marginal donor liver transplantation such as DCD,elderly donor liver,fatty liver,and so on.In recent years,mechanical perfusion has also shown great potential for application in split-liver transplantation,and limited clinical studies have shown outstanding therapeutic effects.Therefore,this paper will summarize the research progress and mechanisms related to the application of mechanical perfusion in split liver transplantation in order to promote the application of mechanical perfusion in split liver transplantation and reduce the damage of the organ during preservation.

Role of pulmonary perfusion magnetic resonance imaging for the diagnosis of pulmonary hypertension:A review

Among five types of pulmonary hypertension,chronic thromboembolic pulmonary hypertension(CTEPH)is the only curable form,but prompt and accurate diagnosis can be challenging.Computed tomography and nuclear medicine-based techniques are standard imaging modalities to non-invasively diagnose CTEPH,however these are limited by radiation exposure,subjective qualitative bias,and lack of cardiac functional assessment.This review aims to assess the methodology,diagnostic accuracy of pulmonary perfusion imaging in the current literature and discuss its advantages,limitations and future research scope.

Efficacy of continuous arterial perfusion chemotherapy combined with transarterial chemoembolization regional arterial thermal perfusion in the treatment of pancreatic cancer with liver metastases

Background:The aim of the study was to investigate the efficacy of continuous transcatheter arterial infusion chemotherapy combined with transarterial chemoembolization(TACE)for the treatment of advanced pancreatic cancer with liver metastasis.Methods:Sixty patients with advanced pancreatic cancer and liver metastases were enrolled in this study.In the treatment group,31patients underwent continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial thermal perfusion,whereas 29 patients included in the control group received intravenous chemotherapy with gemcitabine and S-1.All patients received maintenance chemotherapy with S-1 after 4 cycles of the study regimen.Treatment efficacy,quality of life,survival,and toxicity were evaluated.Results:Efficacy was better in the treatment group than in the control group,as reflected by the objective remission,partial remission,and disease progression rates(all P<0.05).The Eastern Cooperative Oncology Group and Numerical Rating Scale pain scores were also higher in the treatment group(both P<0.05).In survival analysis,the 1-year overall survival rates in the treatment and control groups were64.516%and 10.345%,respectively,whereas the median overall survival times were 16 and 6 months,respectively(both P<0.05).The6-month progression-free survival rates in the treatment and control groups were 77.419%and 13.790%,respectively,and the median progression-free survival times were 12 and 3 months,respectively(both P<0.05).The rates of hematological and nonhematological toxicological adverse effects were also lower in the treatment group(both P<0.05).Although the rate of liver dysfunction was higher in the treatment group,this finding had no adverse effects on prognosis.Conclusions:Continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial perfusion chemotherapy resulted in better efficacy and safety outcomes in patients with pancreatic cancer and liver metastasis,suggesting its utility as a reference method for the clinical treatment of advanced pancreatic cancer.

“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.

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.

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.

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.

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.