The Channel Branches & Network Vessels on the Tianhui Lacquered Meridian Figurine——Taking the Heart-Regulated Channel as an Example

Along with the surge of unearthed medical literature and cultural relics in recent years,a network of channels in the system of medical conduit vessels(meridians) during the early Western Han dynasty has become much clearer gradually.In it,the increasing number of channel branches,network vessels and needle insertion holes(acupoints) is an important feature of the development of channel medicine during the Western Han dynasty.This is not only a reflection of the expanding requirements of the theoretical system of the main trunk channels and other vessels,but also an inevitable result of the continuous enrichment and accumulation of clinical experience.This article integrates the information about channel branches,network vessels,inscriptions,dots and further relics on the Tianhui(天回) Lacquered Meridian Figurine to compare the unearthed literature of the channel genre with the transmitted classical literature about acupuncture.The “Heart-Regulated Channel” in Medical Manuscripts on Bamboo Slips from Tianhui(《天回医简》) serves as an example to explain the occurrence,development and changes of the channel branches and network vessels in the early system of medical channels.

Beginning from the end:the presynaptic terminal as a pathomechanism hub in frontotemporal dementia and amyotrophic lateral sclerosis

Frontotemporal dementia and amyotrophic lateral sclerosis:Frontotemporal dementia(F T D)and amyo t rophic lateral sclerosis(ALS)are neurodegenerative diseases with significant overlapping attributes.While these neurodegenerative diseases affect different neuronal populations(with FTD affecting neurons of the frontal and temporal lobes,and ALS affecting upper and lower motor neurons),these two diseases are complexly intertwined.FTD and ALS exist on a disease spectrum,with shared genetic causes,clinical presentations,and pathologies.

Do medical students studying in the United Kingdom have an adequate factual knowledge of basic life support?

BACKGROUND: Healthcare professionals have a duty to maintain basic life support(BLS) skills. This study aims to evaluate medical students' factual knowledge of BLS and the training they receive.METHODS: A cross-sectional, closed-response questionnaire was distributed to the fi rst-and fourth-year students studying at institutions in the United Kingdom. The paper questionnaire sought to quantify respondent's previous BLS training, factual knowledge of the BLS algorithm using five multiple choice questions(MCQs), and valuate their desire for further BLS training. Students received 1 point for each correctly identifi ed answer to the 5 MCQ's.RESULTS: A total of 3,732 complete responses were received from 21 medical schools. Eighty percent(n=2,999) of students completed a BLS course as part of their undergraduate medical studies. There was a signifi cant difference(P<0.001) in the percentage of the fourth-year students selecting the correct answer in all the MCQ's compared to the fi rst-year students except in identifyingthe correct depth of compressions required during CPR(P=0.095). Overall 10.3%(95% CI 9.9% to 10.7%) of respondents correctly identified the answer to 5 MCQ's on BLS: 9% of the first-year students(n=194) and 12% of the fourth-year students(n=190). On an institutional level the proportion of students answering all MCQ's correctly ranged from 2% to 54% at different universities. Eighty-one percent of students(n=3,031) wished for more BLS training in their curriculum.CONCLUSION: Factual knowledge of BLS is poor among medical students in the UK. There is a disparity in standards of knowledge across institutions and respondents indicating that they would like more training.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

Assessment methods and services for older people with cancer in the United Kingdom

BACKGROUND National cancer strategy calls for comprehensive assessments for older people but current practice across the United Kingdom is not well described.AIM To identify current assessment methods and access to relevant supporting services for older people with cancer.METHODS A web-based survey(SurveyMonkey)targeting health professionals(oncologists,cancer surgeons,geriatricians,nurses and allied health professionals)was distributed January-April 2016 via United Kingdom nationally recognised professional societies.Responses were analysed in frequencies and percentages.Chi Square was used to compare differences in responses between different groups.RESULTS 640 health care professionals responded.Only 14.1%often/always involved geriatricians and 52.0%often/always involved general practitioners in assessments.When wider assessments were used,they always/often influenced decision-making(40.5%)or at least sometimes(34.1%).But 30.5%-44.3%did not use structured assessment methods.Most clinicians favoured clinical history taking.Few used scoring tools and few wished to use them in the future.Most had urgent access to palliative care but only a minority had urgent access to other key supporting professionals(e.g.geriatricians,social workers,psychiatry).69.6%were interested in developing Geriatric Oncology services with geriatricians.CONCLUSION There is variability in assessment methods for older people with cancer across the United Kingdom and variation in perceived access to supporting services.Clinical history taking was preferred to scoring systems.Fostering closer links with geriatricians appears supported.

An Integrated Framework to Analyze Local Decision Making and Adaptation to Sea Level Rise in Coastal Regions in Selsey (UK), Broward County (USA), and Santos (Brazil)

One of the clear signals of the ongoing climate change is sea level rise (SLR). Normal oceanic tides superimposed on a rising sea level and coastal flooding will affect many coastal communities. An international collaboration among Brazil, the United Kingdom, and the United States was designed to evaluate local decision making processes and to open space for local urban managers to reflect on possible actions toward adaption to sea level rise given the historical constraints imposed by administrative and institutional structures. This project focused on the processes that shape adaptation of three coastal communities in three countries. It worked jointly with these communities in defining the problem, examining risks, and understanding the benefits and obstacles that may hinder implementation of adaptation options. The framework was co-designed by an interdisciplinary team that incorporated social and natural scientists from the three countries, including local government officials. The study addressed 1) evaluation of adaptive capacity through participant surveys and 2) physical and cost impact simulations using geospatial models of the built infrastructure and implementation of adaptation options under different hazard scenarios, including 50 and 100-year sea level rise projections and severe storms. Based on the surveys’ results, there is a clear sense of the awareness of each community of the risk of floods due to intense storms, and of the usefulness of engaging early in a process that promotes the understanding of risks, impacts, and costs. A majority of workshop participants prioritized pursuing physical and green infrastructure actions now or within coming years or decades. A positive common aspect of the three sites was the commitment shown by the stakeholders in taking part in the process and evaluating which adaptation measures could be more effective in their cities. While in the US and UK structural solutions and voluntary buyouts were prioritized for the future, Brazil prioritized structural solutions and ecosystems restoration and not voluntary buyouts. All of these are choices to increase resiliency against sea level rise that have a high benefit-cost ratio. The Adaptive Capacity Index (ACI) results illustrate barriers to adaptation action, including technical, economic and political issues that reveal inequalities in adaptive capacity among case studies.

Review of Fault-tolerant Control for Motor Inverter Failure with Operational Quality Considered

In recent years,motor drive systems have garnered increasing attention due to their high efficiency and superior control performance.This is especially apparent in aerospace,marine propulsion,and electric vehicles,where high performance,efficiency,and reliability are crucial.The ability of the drive system to maintain long-term fault-tolerant control(FTC)operation after a failure is essential.The likelihood of inverter failures surpasses that of other components in the drive system,highlighting its critical importance.Long-term FTC operation ensures the system retains its fundamental functions until safe repairs or replacements can be made.The focus of developing a FTC strategy has shifted from basic FTC operations to enhancing the post-fault quality to accommodate the realities of prolonged operation post-failure.This paper primarily investigates FTC strategies for inverter failures in various motor drive systems over the past decade.These strategies are categorized into three types based on post-fault operational quality:rescue,remedy,and reestablishment.The paper discusses each typical control strategy and its research focus,the strengths and weaknesses of various algorithms,and recent advancements in FTC.Finally,this review summarizes effective FTC techniques for inverter failures in motor drive systems and suggests directions for future research.

Is it possible to run after positive affective experiences instead of health benefits without tackling social inequalities?

We recently read the opinion piece titled“Why people should run after positive affective experiences instead of health benefits”,which was carried out by Maltagliati et al.^(1)and published in the Journal of Sport and Health Science.The article started an important discussion about a physical activity(PA)promotion approach that encourages the use of affective experience to PA activity.Although we agree with the authors’point of view and believe that its message can generate an important insight for PA promotion,the authors presented a scenario where behavior change seems to be exclusively dependent on the individual.Recognizing the existence of other barriers to an active lifestyle(e.g.,social inequalities)could enhance the authors’suggested approach because many people live in conditions that reduce their opportunities to engage in affective experiences related to PA;furthermore,affective experiences can vary depending on individual context.

Management of a patient with an unusual trajectory of a temporary trans-venous pacing lead

Perforation of the right ventricle during placement of pacing wires is a welldocumented complication and can be potentially fatal.Use of temporary pacemaker,helical screw leads and steroids use prior to implant are recognised as risk factors for development of post-permanent pacemaker effusion.We reported an unusual case of pacing wire perforating interventricular septum into the left ventricle that occurred during the implant procedure performed in another institution.After the preoperative work-up and transfer to our tertiary cardiothoracic centre,the patient underwent successful surgical management.In conclusion,early recognition and timely diagnosis using advanced multimodality imaging can guide surgical intervention and prevent unfavourable consequences of device-related complications.

Multiuser computational imaging encryption and authentication with OFDM-assisted key management

Single-pixel imaging(SPI)enables an invisible target to be imaged onto a photosensitive surface without a lens,emerging as a promising way for indirect optical encryption.However,due to its linear and broadcast imaging principles,SPI encryption has been confined to a single-user framework for the long term.We propose a multi-image SPI encryption method and combine it with orthogonal frequency division multiplexing-assisted key management,to achieve a multiuser SPI encryption and authentication framework.Multiple images are first encrypted as a composite intensity sequence containing the plaintexts and authentication information,simultaneously generating different sets of keys for users.Then,the SPI keys for encryption and authentication are asymmetrically isolated into independent frequency carriers and encapsulated into a Malus metasurface,so as to establish an individually private and content-independent channel for each user.Users can receive different plaintexts privately and verify the authenticity,eliminating the broadcast transparency of SPI encryption.The improved linear security is also verified by simulating attacks.By the combination of direct key management and indirect image encryption,our work achieves the encryption and authentication functionality under a multiuser computational imaging framework,facilitating its application in optical communication,imaging,and security.

Iron and liver fibrosis: Mechanistic and clinical aspects

Liver fibrosis is characterised by excessive deposition of extracellular matrix that interrupts normal liver functionality. It is a pathological stage in several untreated chronic liver diseases such as the iron overload syndrome hereditary haemochromatosis, viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and diabetes. Interestingly, regardless of the aetiology, iron-loading is frequently observed in chronic liver diseases. Excess iron can feed the Fenton reaction to generate unquenchable amounts of free radicals that cause grave cellular and tissue damage and thereby contribute to fibrosis. Moreover, excess iron can induce fibrosis-promoting signals in the parenchymal and non-parenchymal cells, which accelerate disease progression and exacerbate liver pathology. Fibrosis regression is achievable following treatment, but if untreated or unsuccessful, it can progress to the irreversible cirrhotic stage leading to organ failure and hepatocellular carcinoma, where resection or transplantation remain the only curative options. Therefore,understanding the role of iron in liver fibrosis is extremely essential as it can help in formulating iron-related diagnostic, prognostic and treatment strategies. These can be implemented in isolation or in combination with the current approaches to prepone detection, and halt or decelerate fibrosis progression before it reaches the irreparable stage. Thus, this review narrates the role of iron in liver fibrosis. It examines the underlying mechanisms by which excess iron can facilitate fibrotic responses. It describes the role of iron in various clinical pathologies and lastly,highlights the significance and potential of iron-related proteins in the diagnosis and therapeutics of liver fibrosis.

Autoimmune liver serology:Current diagnostic and clinical challenges

Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseas-es(AiLD),namely autoimmune hepatitis types 1 and 2(AIH-1 and 2),primary biliary cirrhosis(PBC),and the sclerosing cholangitis variants in adults and children.AIH-1 is specified by anti-nuclear antibody(ANA) and smooth muscle antibody(SMA).AIH-2 is specified by antibody to liver kidney microsomal antigen type-1(anti-LKM1) and anti-liver cytosol type 1(anti-LC1).SMA,ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation.PBC is specified by antimitochondrial antibodies(AMA) react-ing with enzymes of the 2-oxo-acid dehydrogenase complexes(chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly react-ing with nuclear pore gp210 and nuclear body sp100.Sclerosing cholangitis presents as at least two variants,first the classical primary sclerosing cholangitis(PSC) mostly affecting adult men wherein the only(and non-specific) reactivity is an atypical perinuclear antineutro-phil cytoplasmic antibody(p-ANCA),also termed peri-nuclear anti-neutrophil nuclear antibodies(p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis(ASC) with serological features resembling those of type 1 AIH.Liver diagnostic serol-ogy is a fast-expanding area of investigation as new purified and recombinant autoantigens,and automatedtechnologies such as ELISAs and bead assays,become available to complement(or even compete with) tradi-tional immunofluorescence procedures.We survey for the first time global trends in quality assurance impact-ing as it does on(1) manufacturers/purveyors of kits and reagents,(2) diagnostic service laboratories that fulfill clinicians' requirements,and(3) the end-user,the physician providing patient care,who must properly interpret test results in the overall clinical context.

Cirrhosis and autoimmune liver disease:Current understanding

Primary biliary cirrhosis(PBC),primary sclerosing cholangitis(PSC) and autoimmune hepatitis(AIH) constitute the classic autoimmune liver diseases(AILDs).While AIH target the hepatocytes,in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells.Persistent liver injury,associated with chronic AILD,leads to un-resolving inflammation,cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts.Liver cirrhosis,and the resultant loss of normal liver function,inevitably ensues.Patients with cirrhosis have higher risks or morbidity and mortality,and that in the decompensated phase,complications of portal hypertension and/or liver dysfunction lead to rapid deterioration.Accurate diagnosis and monitoring of cirrhosis is,therefore of upmost importance.Liver biopsy is currently the gold standard technique,but highly promising non-invasive methodology is under development.Liver transplantation(LT) is an effective therapeutic option for the management of endstage liver disease secondary to AIH,PBC and PSC.LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy;in addition,LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids.

Aetiopathogenesis of autoimmune hepatitis

The histological hallmark of autoimmune hepatitis（AIH） is a dense portal mononuclear cell infiltrate that invades the surrounding parenchyma and comprises T and B lymphocytes,macrophages,and plasma cells.An unknown but powerful stimulus must be promoting the formation of this massive inflammatory cellular reaction that is likely to initiate and perpetuate liver damage.An autoimmune attack can follow different pathways to inflict damage on hepatocytes.Liver damage is likely to be orchestrated by CD4^＋ T lymphocytes recognizing an autoantigenic liver peptide.To trigger an autoimmune response,the peptide must be embraced by an HLA class Ⅱ molecule and presented to naive CD4^＋ T helper（Th0） cells by professional antigen presenting cells,with the co-stimulation of ligand-ligand fostering interaction between the two cells.Th0 cells become activated,differentiate into functional phenotypes according to the cytokines prevailing in the microenvironment and the nature of the antigen,and initiate a cascade of immune reactions determined by the cytokines produced by the activated T cells.Th1 cells,arising in the presence of the macrophage-derived interleukin（IL） -12,secrete mainly IL-2 and interferon-gamma（IFN-γ）,which activate macrophages,enhance expression of HLA classⅠ（increasing liver cell vulnerability to a CD8^＋ T cell cytotoxic attack）,and induce expression of HLA class Ⅱ molecules on hepatocytes.Th2 cells,which differentiate from Th0 if the microenvironment is rich in IL-4,produce mainly IL-4,IL-10,and IL-13 which favour autoantibody production by B lymphocytes.Physiologically,Th1 and Th2 antagonize each other.Th17 cells,a recently described population,arise in the presence of transforming growth factor beta（TGF-β） and IL-6 and appear to have an important effector role in inflammation and autoimmunity.Theprocess of autoantigen recognition is strictly controlled by regulatory mechanisms,such as those exerted by CD4^＋CD25^＋ regulatory T cells,which derive from Th0 in the presence of TGF-β,but in the absence of IL-6.If regulatory mechanisms fail,the autoimmune attack is perpetuated.Over the past three decades different aspects of the above pathogenic scenario have been investigated.In particular,a defect in immunoregulation affecting CD4^＋CD25^＋ regulatory T cells（T-regs） has been demonstrated in AIH,particularly at diagnosis or during relapse.Advances in the study of autoreactive T cells have occurred mostly in AIH type 2,since the knowledge that CYP2D6 is the main autoantigen has enabled the characterization of both CD4 and CD8 T cells targeting this cytochrome.CD4 T cells from patients with type 2 AIH positive for the predisposing HLA allele DRB10701 recognize seven regions of CYP2D6,five of which are also recognized by CD8 T cells.High numbers of IFN-γ producing CD4 T cells and CD8 T cells are associated with biochemical evidence of liver damage,suggesting a combined cellular immune attack.

Pathophysiology of cerebral oedema in acute liver failure

Cerebral oedema is a devastating consequence of acute liver failure(ALF)and may be associated with the development of intracranial hypertension and death.In ALF,some patients may develop cerebral oedema and increased intracranial pressure but progression to lifethreatening intracranial hypertension is less frequent than previously described,complicating less than one third of cases who have proceeded to coma since the advent of improved clinical care.The rapid onset of encephalopathy may be dramatic with the development of asterixis,delirium,seizures and coma.Cytotoxic and vasogenic oedema mechanisms have been implicated with a preponderance of experimental data favouring a cytotoxic mechanism.Astrocyte swelling is the most consistent neuropathological finding in humans with ALF and ammonia plays a definitive role in the development of cytotoxic brain oedema.The mechanism(s)by which ammonia induces astrocyte swelling remains unclear but glutamine accumulation within astrocytes has led to the osmolyte hypothesis.Current evidence also supports an alternate‘Trojan horse’hypothesis,with glutamine as a carrier of ammonia into mitochondria,where its accumulation results in oxidative stress,energy failure and ultimately astrocyte swelling.Although a complete breakdown of the blood-brain barrier is not evident in human ALF,increased permeation to water and other small molecules such as ammonia has been demonstrated resulting from subtle alterations in the protein composition of paracellular tight junctions.At present,there is no fully efficacious therapy for cerebral oedema other than liver transplantation and this reflects our incomplete knowledge of the precise mechanisms underlying this process which remain largely unknown.

Cryptocurrency trading:a comprehensive survey

In recent years,the tendency of the number of financial institutions to include crypto-currencies in their portfolios has accelerated.Cryptocurrencies are the first pure digital assets to be included by asset managers.Although they have some commonalities with more traditional assets,they have their own separate nature and their behaviour as an asset is still in the process of being understood.It is therefore important to summarise existing research papers and results on cryptocurrency trading,including available trading platforms,trading signals,trading strategy research and risk management.This paper provides a comprehensive survey of cryptocurrency trading research,by covering 146 research papers on various aspects of cryptocurrency trading(e.g.,cryptocurrency trading systems,bubble and extreme condition,prediction of volatility and return,crypto-assets portfolio construction and crypto-assets,technical trading and others).This paper also analyses datasets,research trends and distribution among research objects(contents/properties)and technologies,concluding with some promising opportunities that remain open in cryptocurrency trading.

A Finite and Instantaneous Screw Based Approach for Topology Design and Kinematic Analysis of 5-Axis Parallel Kinematic Machines

Unifying the models for topology design and kinematic analysis has long been a desire for the research of parallel kinematic machines(PKMs). This requires that analytical description, formulation and operation for both finite and instantaneous motions are performed by the same mathematical tool. Based upon finite and instantaneous screw theory, a unified and systematic approach for topology design and kinematic analysis of PKMs is proposed in this paper. Using the derivative mapping between finite and instantaneous screws built in the authors’ previous work, the finite and instantaneous motions of PKMs are analytically described by the simple and non?redundant screws in quasi?vector and vector forms. And topological and parametric models of PKMs are algebraically formulated and related. These related topological and parametric models are ready to do type synthesis and kinematic analysis of PKMs under the unified framework of screw theory. In order to show the validity of the proposed approach, a kind of two?translational and three?rotational(2T3R)5?axis PKMs is taken as example. Numerous new structures of the 2T3R PKMs are synthe?sized as the results of topology design, and their Jacobian matrix is obtained easily for parameter optimization and performance evaluation. Some of the synthesized PKMs have outstanding capabilities in terms of large workspaces and flexible orientations, and have great potential for industrial applications of machining and manufacture. Among them, METROM PKM is a typical example which has attracted a lot of attention from global companies and already been developed as commercial products. The approach is a general and unified approach that can be used in the innovative design of different kinds of PKMs.

Molecularly targeted therapy for advanced hepatocellular carcinoma-a drug development crisis?

Hepatocellular carcinoma is the fastest growing cause of cancer related death globally. Sorafenib,a multitargeted kinase inhibitor,is the only drug proven to improve outcomes in patients with advanced disease offering modest survival benefit. Although comprehensive genomic mapping has improved understanding of the genetic aberrations in hepatocellular cancer(HCC),this knowledge has not yet impacted clinical care. The last few years have seen the failure of several first and second line phase Ⅲ clinical trials of novel molecularly targeted therapies,warranting a change in the way new therapies are investigated in HCC. Potential reasons for these failures include clinical and molecular heterogeneity,trial design and a lack of biomarkers. This review discusses the current crisis in HCC drug development and how we should learn from recent trial failures to develop a more effective personalised treatment paradigm for patients with HCC.

Cartilage oligomeric matrix protein: A novel non-invasive marker for assessing cirrhosis and risk of hepatocellular carcinoma

AIM: To assess serum cartilage oligomeric matrix protein(COMP) as a marker of cirrhosis and risk of progression to hepatocellular carcinoma(HCC). METHODS: A COMP enzyme-linked immunosorbentassay was used to test 187 patients with chronic liver diseases at the time point of first evaluation. The selected patients included 72 with chronic hepatitis B infection, 75 with chronic hepatitis C infection, 22 with primary biliary cirrhosis, 7 with autoimmune hepatitis type 1, and 11 with alcoholic liver disease. Demographic, biochemical, histological and clinical characteristics of the patients were recorded at the first evaluation. One hundred and forty-seven patients were followed for a median [interquartile range(IQR)] duration of 96.5(102) mo. The clinical, biochemical and histological data, as well as the development of cirrhosis, HCC according to internationally accepted criteria and in case of death, a liver-related cause during the follow-up period, were recorded at the electronic database of our clinic. COMP determination was also performed in 43 healthy individuals who served as the control study group.RESULTS: COMP positivity(> 15 U/L) was detected in 22%-36% among chronic liver disease groups. Strikingly, almost 83% of COMP-positive patients were cirrhotic at baseline, independently of cause of liver disease. Among the patients who developed HCC during follow-up, 73.7%(14/19) were COMP positive at baseline. COMP positivity was significantly associated with older age(P < 0.001), advanced fibrosis(P = 0.001) and necroinflammatory activity(P = 0.001), higher aspartate aminotransferase(P < 0.001), alanine aminotransferase(P < 0.02), γ-glutamyl transpeptidase(P = 0.003), alkaline phosphatase(P = 0.001), bilirubin(P < 0.05), international normalized ratio(P = 0.002) and alpha-fetoprotein levels(P < 0.02), and lower albumin(P < 0.001), and platelet count(P = 0.008). COMP levels [median(IQR)] were significantly higher in cirrhotics compared to non-cirrhotics [13.8(7.9) U/L vs 9.8(4.6) U/L, respectively; P < 0.001]. On multivariate logistic regression analysis, COMP-positivity was independently associated only with cirrhosis(OR = 4.40, 95%CI: 1.33-14.69, P = 0.015). Kaplan-Meier analysis showed that COMP positivity was significantly associated with HCC development(P = 0.007) and higher incidence of liver-related death(P < 0.001). CONCLUSION: Elevated COMP levels are strongly associated with cirrhosis and HCC progression. Serum COMP is a new promising non-invasive biomarker for HCC risk assessment in surveillance programs.

Potential triggering factors of acute liver failure as a first manifestation of autoimmune hepatitis-a single center experience of 52 adult patients

AIM To investigate potential triggering factors leading to acute liver failure(ALF) as the initial presentation of autoimmune hepatitis(AIH).METHODS A total of 565 patients treated at our Department between 2005 and 2017 for histologically-proven AIH were retrospectively analyzed. However, 52 patients(9.2%) fulfilled the criteria for ALF defined by the "American Association for the Study of the Liver(AASLD)". According to this definition, patients with "acute-on-chronic" or "acute-on-cirrhosis" liver failure were excluded. Following parameters with focus on potential triggering factors were evaluated: Patients' demographics, causation of liver failure, laboratory data(liver enzymes, MELD-score, autoimmune markers, virus serology), liver histology, immunosuppressive regime, and finally, outcome of our patients.RESULTS The majority of patients with ALF were female(84.6%) and mean age was 43.6 ± 14.9 years. Interestingly, none of the patients with ALF was positive for antiliver kidney microsomal antibody(LKM). We could identify potential triggering factors in 26/52(50.0%) of previously healthy patients presenting ALF as their first manifestation of AIH. These were drug-induced ALF(57.7%), virus-induced ALF(30.8%), and preceding surgery in general anesthesia(11.5%), respectively. Unfortunately, 6 out of 52 patients(11.5%) did not survive ALF and 3 patients(5.7%) underwent liver transplantation(LT). Comparing data of survivors and patients with non-recovery following treatment, MELDscore(P < 0.001), age(P < 0.05), creatinine(P < 0.01), and finally, ALT-values(P < 0.05) reached statistical significance. CONCLUSION Drugs, viral infections, and previous surgery may trigger ALF as the initial presentation of AIH. Advanced age and high MELD-score were associated with lethal outcome.