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.

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.

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].

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.

Artificial intelligence software for assessing brain ischemic penumbra/core infarction on computed tomography perfusion:A real-world accuracy study

BACKGROUND With the increasingly extensive application of artificial intelligence(AI)in medical systems,the accuracy of AI in medical diagnosis in the real world deserves attention and objective evaluation.AIM To investigate the accuracy of AI diagnostic software(Shukun)in assessing ischemic penumbra/core infarction in acute ischemic stroke patients due to large vessel occlusion.METHODS From November 2021 to March 2022,consecutive acute stroke patients with large vessel occlusion who underwent mechanical thrombectomy(MT)post-Shukun AI penumbra assessment were included.Computed tomography angiography(CTA)and perfusion exams were analyzed by AI,reviewed by senior neurointerventional experts.In the case of divergences among the three experts,discussions were held to reach a final conclusion.When the results of AI were inconsistent with the neurointerventional experts’diagnosis,the diagnosis by AI was considered inaccurate.RESULTS A total of 22 patients were included in the study.The vascular recanalization rate was 90.9%,and 63.6%of patients had modified Rankin scale scores of 0-2 at the 3-month follow-up.The computed tomography(CT)perfusion diagnosis by Shukun(AI)was confirmed to be invalid in 3 patients(inaccuracy rate:13.6%).CONCLUSION AI(Shukun)has limits in assessing ischemic penumbra.Integrating clinical and imaging data(CT,CTA,and even magnetic resonance imaging)is crucial for MT decision-making.

Normothermic regional perfusion mobile teams in controlled donation after circulatory death pathway: Evidence and peculiarities

To facilitate the implementation of controlled donation after circulatory death(cDCD)programs even in hospitals not equipped with a local Extracorporeal Membrane Oxygenation(ECMO)team(Spokes),some countries and Italian Regions have launched a local cDCD network with a ECMO mobile team who move from Hub hospitals to Spokes for normothermic regional perfusion(NRP)implantation in the setting of a cDCD pathway.While ECMO teams have been clearly defined by the Extracorporeal Life Support Organization,regarding composition,responsibilities and training programs,no clear,widely accepted indications are to date available for NRP teams.Although existing NRP mobile networks were developed due to the urgent need to increase the number of cDCDs,there is now the necessity for transplantation medicine to identify the peculiarities and responsibility of a NRP team for all those centers launching a cDCD pathway.Thus,in the present manuscript we summarized the character-istics of an ECMO mobile team,highlighting similarities and differences with the NRP mobile team.We also assessed existing evidence on NRP teams with the goal of identifying the characteristic and essential features of an NRP mobile team for a cDCD program,especially for those centers who are starting the program.Differences were identified between the mobile ECMO team and NRP mobile team.The common essential feature for both mobile teams is high skills and experience to reduce complications and,in the case of cDCD,to reduce the total warm ischemic time.Dedicated training programs should be developed for the launch of de novo NRP teams.

Matched pair analysis of the effect of longer hypothermic machine perfusion time on kidney transplant outcomes

BACKGROUND Hypothermic machine perfusion(HMP)has demonstrated benefits in terms of early kidney transplant function compared to static cold storage.While longer preservation times have shown detrimental effects,a previous paired study indicated that longer pump times(the second kidney in a pair)might lead to improved outcomes.AIM To revisit the prior paired study's somewhat unexpected results by reviewing our program's experience.METHODS A total of 61 pairs of transplant recipients who received kidneys from the same donor(2012-2021)were analyzed.Patients were divided into two groups depending on whether they were transplanted first(K1)or second(K2).Therefore,the patients in each pair had identical donor characteristics,except for time on the pump.Statistical analyses included Kaplan-Meyer analysis and paired tests,including McNemar's test,student's paired t-test,or Wilcoxon's test,as appropriate.RESULTS The two groups of recipients had similar demographics(age,body mass index,diabetes,time on dialysis,sensit-ization and retransplants).Cold ischemic times for K1 and K2 were 8.9(95%CI:7.9,9.8)and 14.7 hours(13.7,15.8)(P<0.0001),respectively.Overall,K2 had a higher rate of freedom from biopsy-proven acute rejection at 1 year(P=0.015).Delayed graft function was less common in K2,12/61(20%)than in K1,20/61(33%)(P=0.046).Finally,K2 showed a higher graft survival than K1(P=0.023).CONCLUSION Our results agree with a previous study that suggested possible advantages to longer pump times.Both studies should encourage further research into HMP's potential anti-inflammatory effect.

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.

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.

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.

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.

Liver graft preservation methods during cold ischemia phase and normothermic machine perfusion

The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960 s is the mainstay and the golden standard for donated organ protection. Hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. Normothermic machine perfusion(NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury.Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose.Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.

Concise review of machine perfusion in liver transplantation

With the advances and clinical growth in liver transplantation over the last four decades the focus on expanding deceased donor organs has been in need of scientific research.In the past ten years several researchers have looked at the domain of machine perfusion as it applies to deceased donor livers.The following review focuses on the clinical trials and recent advances that will likely have the earliest entrance into the clinical arena.

Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion

Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(LSEC). Recent evidence suggests that LSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI.