Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study

BACKGROUND The treatment outcome of transarterial chemoembolization(TACE)in unresectable hepatocellular carcinoma(HCC)varies greatly due to the clinical heterogeneity of the patients.Therefore,several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE(re-TACE).AIM To investigate the correlations between prognostic systems and radiological response,compare the predictive abilities,and integrate them in sequence for outcome prediction.METHODS This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016.The Hepatoma Arterial-embolization Prognostic(HAP)score system and its modified versions(mHAP,mHAP2 and mHAP3),as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival(OS)prediction for first TACE.The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART(assessment for re-treatment with TACE)and ABCR(alpha-fetoprotein,Barcelona Clinic Liver Cancer,Child-Pugh and Response)systems for post re-TACE survival(PRTS).RESULTS All the prognostic systems were correlated with radiological response achieved by first TACE,and the six-and-twelve criteria exhibited the highest correlation(Spearman R=0.39,P=0.026)and consistency(Kappa=0.14,P=0.019),with optimal performance by area under the receiver operating characteristic curve of 0.71[95%confidence interval(CI):0.68-0.74].With regard to the prediction of OS,the mHAP3 system identified patients with a favorable outcome with the highest concordance(C)-index of 0.60(95%CI:0.57-0.62)and the best area under the receiver operating characteristic curve at any time point during follow-up;whereas,PRTS was well-predicted by the ABCR system with a C-index of 0.61(95%CI:0.59-0.63),rather than ART.Finally,combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo,compared with non-candidates with a median PRTS of 20.0 mo(logrank test P<0.001).CONCLUSION Radiological response to TACE is closely associated with tumor burden,but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.

Serum urate is associated with an increased risk of inflammatory bowel disease: A bidirectional Mendelian randomization study

BACKGROUND Previous studies have indicated bidirectional associations between urate levels and inflammatory bowel disease(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD).However,it remains unclear whether the observations are causal because of confounding factors.AIM To investigate the causal associations between urate levels and IBD using bidirec-tional Mendelian randomization(MR).METHODS Independent genetic variants for urate levels and IBD were selected as instru-mental variables from published genome-wide association studies(GWASs).Summary statistics for instrument-outcome associations were retrieved from three separate databases for IBD(the UK Biobank,the FinnGen database and a large GWAS meta-analysis)and one for urate levels(a large GWAS meta-analysis).MR analyses included the inverse-variance-weighted method,weighted-median estimator,MR-Egger and sensitivity analyses(MR-PRESSO).A meta-analysis was also conducted to merge the data from separate outcome databases using a fixed-effects model.RESULTS Genetically higher serum urate levels were strongly associated with an increased risk of UC[odds ratio(OR):1.95,95%confidence interval(CI):1.86-2.05]after outlier correction,and the ORs(95%CIs)for IBD and CD were 0.94(95%CI:0.86-1.03)and 0.91(95%CI:0.80-1.04),respectively.Animal studies have confirmed the positive association between urate levels and UC.Moreover,genetically predicted IBD was inversely related to urate levels(OR:0.97,95%CI:0.94-0.99).However,no association was observed between genetically influenced UC or CD and urate levels.CONCLUSION Urate levels might be risk factors for UC,whereas genetically predicted IBD was inversely associated with urate levels.These findings provide essential new insight for treating and preventing IBD.

Diagnostic performance of narrow-band imaging international colorectal endoscopic and Japanese narrow-band imaging expert team classification systems for colorectal cancer and precancerous lesions

BACKGROUND In recent years,two new narrow-band imaging(NBI)classifications have been proposed:The NBI international colorectal endoscopic(NICE)classification and Japanese NBI expert team(JNET)classification.Most validation studies of the two new NBI classifications were conducted in classification setting units by experienced endoscopists,and the application of use in different centers among endoscopists with different endoscopy skills remains unknown.AIM To evaluate clinical application and possible problems of NICE and JNET classification for the differential diagnosis of colorectal cancer and precancerous lesions.METHODS Six endoscopists with varying levels of experience participated in this study.Eighty-seven consecutive patients with a total of 125 lesions were photographed during non-magnifying conventional white-light colonoscopy,non-magnifying NBI,and magnifying NBI.The three groups of endoscopic pictures of each lesion were evaluated by the six endoscopists in randomized order using the NICE and JENT classifications separately.Then we calculated the six endoscopists’sensitivity,specificity,accuracy,positive predictive value,and negative predictive value for each category of the two classifications.RESULTS The sensitivity,specificity,and accuracy of JNET classification type 1 and 3 were similar to NICE classification type 1 and 3 in both the highly experienced endoscopist(HEE)and less-experienced endoscopist(LEE)groups.The specificity of JNET classification type 1 and 3 and NICE classification type 3 in both the HEE and LEE groups was>95%,and the overall interobserver agreement was good in both groups.The sensitivity of NICE classification type 3 lesions for diagnosis of SM-d carcinoma in the HEE group was significantly superior to that in the LEE group(91.7%vs 83.3%;P=0.042).The sensitivity of JNET classification type 2B lesions for the diagnosis of high-grade dysplasia or superficial submucosal invasive carcinoma in the HEE and LEE groups was 53.8%and 51.3%,respectively.Compared with other types of JNET classification,the diagnostic ability of type 2B was the weakest.CONCLUSION The treatment strategy of the two classification type 1 and 3 lesions can be based on the results of endoscopic examination.JNET type 2B lesions need further examination.

Effects of exercise by type and duration on quality of life in patients with digestive system cancers:A systematic review and network meta-analysis

Background:There is scant evidence regarding the effects of exercise type and duration on quality of life(QoL)in digestive system cancer(DSC)survivors.We aim to investigate the optimal type and duration of exercise to improve QoL for DSC survivors through a systematic review and network meta-analysis.Methods:A systematic literature search of PubMed,Embase,and Web of Science was performed.Eligibility for study inclusion was limited to studies that were randomized controlled trials involving all kinds of exercise in adult patients with DSCs,and the comparator was in standard care or other types of exercise.The primary outcome was QoL,including general health,physical health,mental health,and role function.Secondary outcomes included cancer-related symptoms such as fatigue,insomnia,depression,anxiety,and duration of hospital stay.The network meta-analyses were performed using a random-effect model.Results:The analysis included 32 eligible articles and a total of 2558 participants.Our primary outcome indicated that short-term aerobic exercise significantly enhanced general health(standardized mean difference(SMD)=0.66,95%credible intervals(Crls):0.05 to 1.30),and also contributed to a better mental health(SMD=0.38,95%CrI:-0.05 to 0.81)and role function(SMD=0.48,95%CrI:-0.27 to 1.20).Although without significant changes,short-term resistance exercise tended to increase the physical health of patients with DSCs(SM=0.69,95%CrI:-0.07 to 1.50)and effective in alleviating fatigue(SMD=-0.77,95%CrI:-1.50 to 0.01).Short-term aerobic exercise was related to a lower score of insomnia(SMD=-1.20,95%CrI:-2.40 to 0.06),depression(SMD=-0.51,95%CrI:-1.50 to 0.45),and anxiety(SMD=-0.45,95%CrI:-1.30 to 0.34).All types of exercise related to a trend of declined hospital stays(-0.87 to-5.00 day).Long-term resistance exercise,however,was negatively associated with general health(SMD=-0.33,95%CrI:-1.70 to 1.00),physical health(SMD=-0.18,95%CrI:-1.30to 0.90),and role function(SMD=-1.20,95%CrI:-2.50 to 0.11).Conclusion:This study suggests that short-term aerobic exercise,with or without resistance exercise programs,enhances QoL(especially for general health)as well as relieves cancer-related symptoms for DSC survivors,while long-term resistance exercise may have negative effects,and thus should be adopted cautiously.These results provide important evidence for the management of DSCs.

DNA methylation biomarkers for early detection of gastric and colorectal cancers

Cancer is one of the leading causes of death worldwide.The early diagnosis of cancer remains one of the greatest cancer research challenges.Epigenetic alterations,such as altered DNA methylation,that occur during the early stages of carcinogenesis have been proposed as candidate cancer biomarkers.In recent years detection of small amounts of methylated DNA in samples,including blood and stool,has demonstrated the feasibility of DNA methylation as a molecular cancer biomarker.The translational promise of aberrant DNA methylation includes screening and detecting cancer,evaluating prognosis,assessing treatment efficacy,and detecting minimal residual disease(Figure 1).

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

Burden of colorectal cancer in China, 1990-2017: Findings from the Global Burden of Disease Study 2017

Objective: Our goal is to analyze the trend of colorectal cancer(CRC) regarding the death, incidence and prevalence rates over time, and to provide epidemiological knowledge basis for health policy revision by comparing data about fatal outcomes of CRC in 2017 to those data in 1990, which was extracted from the Global Burden of Disease(GBD).Methods: The time trend and changes of CRC burden from 1990 to 2017 were measured by using the methods and results from the Institute for Health Metrics and Evaluation(IHME) GBD 2017, based on the rates of death,incidence and prevalence.Results: The death rate of CRC is 13.24/100,000, accounting for 1.79% of total deaths in China in 2017. In1990, CRC ranked 21 st in all causes of death in China compared to its 11 th ranking in 2017. The death, incidence and prevalence rate of CRC were standardized by the age scale of the global population in 2010, the change of standardized death rate of CRC was not significant, from 9.33/100,000 in 1990 to 10.10/100,000 in 2017. The standardized incidence rate of CRC significantly increased from 12.18/100,000 in 1990 to 22.42/100,000 in 2017.The standardized prevalence rate of CRC significantly increased from 44.55/100,000 in 1990 to 118.40/100,000 in2017. The trend of the prevalence rate in both genders grow higher in 2017 compared to the 1990, resulting in141.6%, 209.8% and 189.0% for the studied three age groups(15-49, 50-69 and 70+ years old), respectively. The death rate increased in the age groups of 50-69 and 70+ years in both genders(8.6% and 31.0% respectively), in contrast to a decrease of death rate in the age group of 15-49 years old(-10.8%).Conclusions: China experienced a stunning increase in terms of incidence and prevalence rate of CRC from1990 to 2017. To decrease the burden of CRC, prevention and management of known risk factors should be promoted through national polices.

Validation of the six-and-twelve criteria among patients with hepatocellular carcinoma and performance score 1 receiving transarterial chemoembolization

BACKGROUND Transarterial chemoembolization(TACE)is recommended for patients with intermediate hepatocellular carcinoma(HCC)according to treatment guidelines.However,a large number of patients with advanced HCC also receive TACE in clinical practice,especially for those with liver-confined HCC and Eastern Cooperative Oncology Group score(ECOG)1.In view of previous studies,such patients have different prognoses from advanced HCC patients with macrovascular invasion or extrahepatic spread;therefore,patients with ECOG 1 alone might be classified into the intermediate stage and benefit from TACE treatment,but a study particularly focusing on such patients and exploring the effectiveness of TACE therapy is lacking.AIM To investigate treatment outcomes of TACE in HCC patients with ECOG 1 alone and propose a specific prognostic model.METHODS Patients from 24 Chinese tertiary hospitals were selected in this nationwide multicenter observational study from January 2010 to May 2016.Overall survival(OS)was estimated using Kaplan–Meier curves and compared by the log-rank test.Multivariate Cox regression was used to develop the potential prognostic models.The discriminatory ability of the models was compared and validated in various patient subgroups.The individual survival prediction for six-and-twelve(6&12)criteria,defined as the algebraic sum of tumor size(cm)and tumor number,was illustrated by contour plot of 3-year survival probability and nomogram.RESULTS A total of 792 eligible patients were included.During follow-up,median OS reached 18.9 mo[95%confidence interval(CI):16.9-21.0].Three independent multivariate analyses demonstrated that tumor size,tumor number,α-fetoprotein level,albumin–bilirubin grade and total bilirubin were prognostic factors of OS(P<0.05).The previously proposed 6&12 criteria was comparable or even better than currently proposed with the highest predictive ability.In addition,the 6&12 criteria was correlated with OS in various subgroups of patients.The patients were stratified into three strata with score≤6,>6 but≤12,and>12 with different median OS of 39.8 mo(95%CI:23.9-55.7),21.1 mo(95%CI:18.4-23.8)and 9.8 mo(95%CI:8.3-11.3),respectively(P<0.001).CONCLUSION TACE is effective for advanced HCC patients with ECOG 1 alone,and the 6&12 criteria may help with clinical decision-making.

Liver transplantation for severe portopulmonary hypertension: A case report and literature review

BACKGROUND Portopulmonary hypertension(PoPH)is not uncommon in patients waiting for liver transplantation(LT).Severe PoPH has a very high perioperative mortality rate and is still considered a contraindication for LT.Many patients with liver disease require but cannot receive LT due to severe PoPH and eventually died.We report a patient with severe PoPH who underwent successful LT and had near normal pulmonary pressure without drug treatment.CASE SUMMARY A 39-year-old woman was hospitalized with the chief complaint of jaundice and exertional dyspnea and fatigue.Caroli disease and liver cirrhosis was diagnosed 6 years previously.Her liver disease met the criteria for LT.However,right heart catheterization showed that her mean pulmonary artery pressure was increased at 50 mmHg,pulmonary vascular resistance was 460 dyn?s/cm5 and pulmonary artery wedge pressure was 20 mmHg,which may have been the reasons for her chief complaint.The patient was diagnosed with severe PoPH and was not listed for LT immediately.After 5 mo of pharmacotherapy,her severe PoPH was moderate,and she underwent successful LT.Pulmonary artery pressure steadily decreased according to post-operative echocardiographic monitoring and drugs CONCLUSION The safety of LT can be greatly improved by reducing mean pulmonary artery pressure to a low level,and LT may cure PoPH.

Novel approach for the diagnosis of occult cytomegalovirus cholangitis after pediatric liver transplantation:A case report

BACKGROUND Cytomegalovirus(CMV)infection is a common infection in liver transplant recipients,which is related to chronic rejection and biliary complications.It is often diagnosed based on serum CMV-DNA or CMV pp65.To our knowledge,this is the first report of the successful treatment of occult CMV cholangitis in a pediatric liver transplantation(LT)recipient.CASE SUMMARY A 7-mo-old baby girl received LT due to biliary atresia and cholestasis cirrhosis.At 1 mo following LT,the patient suffered from aggravated jaundice with no apparent cause.As imaging results showed intrahepatic and extrahepatic bile duct dilatation,the patient was diagnosed with biliary complications and percutaneous cholangiography and biliary drainage was performed.However,there was little biliary drainage and her liver function deteriorated.CMV-DNA was isolated from the bile with the surprising outcome that 3×106 copies/mL were present,whereas the CMV-DNA in serum was negative.Following antiviral therapy with ganciclovir,she gradually recovered and bilirubin decreased to normal levels.During the 4-year follow-up period,her liver function remained normal.CONCLUSION Bile CMV sampling can be used for the diagnosis of occult CMV infection,especially in patients with negative serum CMV-DNA and CMV pp65.Testing for CMV in the biliary tract may serve as a novel approach for the diagnosis of cholestasis post-LT.Timely diagnosis and treatment will decrease the risk of graft loss.

Concomitant extrahepatic autoimmune diseases do not compromise the long-term outcomes of primary biliary cholangitis

Background:Primary biliary cholangitis(PBC)patients often have concomitant extrahepatic autoimmune(EHA)diseases including Sjögren’s syndrome(SS),systemic sclerosis(SSc),rheumatoid arthritis(RA),and autoimmune thyroid disease.The present study aimed to describe the prevalence of EHA diseases in PBC and explore the impact of EHA diseases on the long-term outcomes of PBC in Chinese patients.Methods:Medical records of PBC patients diagnosed in our institute were retrospectively reviewed.Pa-tients were followed up by a standardized telephone interview.The endpoints were defined as liver-related death and/or liver transplantation.Results:Totally 247 of the 985(25.1%)PBC patients enrolled in the study had at least one concomi-tant EHA disease.Sjögren’s syndrome(n=140,14.2%)was the most frequent one,followed by rheuma-toid arthritis(RA)(n=56,5.7%)and Hashimoto’s thyroiditis(n=45,4.6%).Patients with EHA dis-eases were more common in females(P<0.001)and in those with a family history of autoimmune disease(P=0.017).Overall,no differences were found between PBC patients with and without EHA dis-eases in terms of biochemical response rates to ursodeoxycholic acid,the incidence of hepatic events,or transplant-free survival.RA and EHA≥2 were protective factors for hepatic events in univariate Cox analysis,but the results became insignificant in multivariate analysis.Conclusions:Concomitant EHA diseases were common in PBC patients but did not compromise the long-term outcomes of PBC.

Cholangiojejunostomy for multiple biliary ducts in living donor liver transplantation: A case report

BACKGROUND Laparoscopic living donor hepatectomy(LLDH)has been successfully carried out in several transplant centers.Biliary reconstruction is key in living donor liver transplantation(LDLT).Reliable biliary reconstruction can effectively prevent postoperative biliary stricture and leakage.Although preoperative magnetic resonance cholangiopancreatography and intraoperative indocyanine green cholangiography have been shown to be helpful in determining optimal division points,biliary variability and limitations associated with LLDH,multiple biliary tracts are often encountered during surgery,which inhibits biliary reconstruction.A reliable cholangiojejunostomy for multiple biliary ducts has been utilized in LDLT.This procedure provides a reference for multiple biliary reconstructions after LLDH.CASE SUMMARY A 2-year-old girl diagnosed with ornithine transcarbamylase deficiency required liver transplantation.Due to the scarcity of deceased donors,she was put on the waiting list for LDLT.Her father was a suitable donor;however,after a rigorous evaluation,preoperative magnetic resonance cholangiopancreatography examination of the donor indicated the possibility of multivessel variation in the biliary tract.Therefore,a laparoscopic left lateral section was performed on the donor,which met the estimated graft-to-recipient weight ratio.Under intraoperative indocyanine green cholangiography,4 biliary tracts were confirmed in the graft.It was difficult to reform the intrahepatic bile ducts due to their openings of more than 5 mm.A reliable cholangiojejunostomy was,therefore,utilized:Suture of the jejunum to the adjacent liver was performed around the bile duct openings with 6/0 absorbable sutures.At the last follow-up(1 year after surgery),the patient was complication-free.CONCLUSION Intrahepatic cholangiojejunostomy is reliable for multiple biliary ducts after LLDH in LDLT.

Impact of cytomegalovirus infection on biliary disease after liver transplantation-maybe an essential factor

BACKGROUND Cytomegalovirus(CMV)infection is common in liver transplant(LT)_recipients,and biliary complications occur in a large number of patients.It has been reported that CMV-DNA is more detectable in bile than in blood.AIM To investigate the effects of CMV infection on biliary complications by comparing the levels of CMV-DNA in the bile and blood of patients after LT.METHODS We conducted a retrospective analysis of 57 patients who underwent LT,10 of these patients had no biliary complications and 47 patients had biliary complications.We also compared the levels of CMV-DNA in patients’bile and blood,which were sampled concurrently.We used RNAscope technology to identify CMV in paraffin-embedded liver sections.RESULTS CMV-DNA was not detected in bile samples and was detected in 2 blood samples from patients without biliary complications.In the 47 patients with biliary complications,CMV-DNA was detected in 22 bile samples and 8 blood samples,both bile and blood samples were positive for CMV-DNA in 6 patients.The identification rate of CMV-DNA in blood was 17.0%,and was 46.8%in bile.Moreover,tissue samples from 4 patients with biliary complications tested positive using RNAscope technology but were negative with hematoxylin and eosin staining.During the follow-up period,graft failure occurred in 13 patients with biliary complications,8 of whom underwent retransplantation,and 3 died.CMV-DNA in bile was detected in 9 of 13 patients with graft failure.CONCLUSION In patients with biliary complications,the identification rate of CMV-DNA in bile was higher than that in blood.Blood CMV-DNA negative patients with biliary complications should still be monitored for CMV-related biliary tract diseases.Potential occult CMV infection may also be a contributing etiological factor in the development of graft failure.

Predictive value of alarm symptoms in Rome IV irritable bowel syndrome:A multicenter cross-sectional study

BACKGROUND Irritable bowel syndrome(IBS)is a common functional bowel disease that shares features with many organic diseases and cannot be accurately diagnosed by symptom-based criteria.Alarm symptoms have long been applied in the clinical diagnosis of IBS.However,no study has explored the predictive value of alarm symptoms in suspected IBS patients based on the latest Rome IV criteria.AIM To investigate the predictive value of alarm symptoms in suspected IBS patients based on the Rome IV criteria.METHODS In this multicenter cross-sectional study,we collected data from 730 suspected IBS patients evaluated at 3 tertiary care centers from August 2018 to August 2019.Patients with IBS-like symptoms who completed colonoscopy during the study period were initially identified by investigators through medical records.Eligible patients completed questionnaires,underwent laboratory tests,and were assigned to the IBS or organic disease group according to colonoscopy findings and pathology results(if a biopsy was taken).Independent risk factors for organic disease were explored by logistic regression analysis,and the positive predictive value(PPV)and missed diagnosis rate were calculated.RESULTS The incidence of alarm symptoms in suspected IBS patients was 75.34%.Anemia[odds ratio(OR)=2.825,95%confidence interval(CI):1.273-6.267,P=0.011],fecal occult blood[OR=1.940(95%CI:1.041-3.613),P=0.037],unintended weight loss(P=0.009),female sex[OR=0.560(95%CI:0.330-0.949),P=0.031]and marital status(P=0.030)were independently correlated with organic disease.The prevalence of organic disease was 10.41%in suspected IBS patients.The PPV of alarm symptoms for organic disease was highest for anemia(22.92%),fecal occult blood(19.35%)and unintended weight loss(16.48%),and it was 100%when these three factors were combined.The PPV and missed diagnosis rate for diagnosing IBS were 91.67%and 74.77%when all alarm symptoms were combined with Rome IV and 92.09%and 34.10%when only fecal occult blood,unintended weight loss and anemia were combined with Rome IV,respectively.CONCLUSION Anemia,fecal occult blood and unintended weight loss have high predictive value for organic disease in suspected IBS patients and can help identify patients requiring further examination but are not recommended as exclusion criteria for IBS.

Development and validation of a novel model to predict liver-related mortality in patients with idiosyncratic drug-induced liver injury

Background: Early identification of patients with high mortality risk is critical for optimizing the clinical management of drug-induced liver injury(DILI). We aimed to develop and validate a new prognostic model to predict death within 6 months in DILI patients. Methods: This multicenter study retrospectively reviewed the medical records of DILI patients admitted to three hospitals. A DILI mortality predictive score was developed using multivariate logistic regression and was validated with area under the receiver operating characteristic curve(AUC). A high-mortality-risk subgroup was identified according to the score. Results: Three independent DILI cohorts, including one derivation cohort( n = 741) and two validation cohorts( n = 650, n = 617) were recruited. The DILI mortality predictive(DMP) score was calculated using parameters at disease onset as follows: 1.913 × international normalized ratio + 0.060 × total bilirubin(mg/d L) + 0.439 × aspartate aminotransferase/alanine aminotransferase – 1.579 × albumin(g/d L) –0.006 × platelet count(109/L) + 9.662. The predictive performance for 6-month mortality of DMP score was desirable, with an AUC of 0.941(95% CI: 0.922-0.957), 0.931(0.908-0.949) and 0.960(0.942-0.974) in the derivation, validation cohorts 1 and 2, respectively. DILI patients with a DMP score ≥ 8.5 were stratified into high-risk group, whose mortality rates were 23-, 36-, and 45-fold higher than those of other patients in the three cohorts. Conclusions: The novel model based on common laboratory findings can accurately predict mortality within 6 months in DILI patients, which should serve as an effective guidance for management of DILI in clinical practice.

活体肝脏捐献者生命质量影响因素的系统综述

目的旨在对活体肝脏捐献者捐献后生命质量的影响因素进行梳理和归纳,为临床护理制订有针对性的干预措施提供参考依据。方法对PubMed、EMBASE、CINHAL、Web of Science和ProQuest数据库进行检索。检索时间为建库至2022年6月,纳入经过同行评审的英文文献,包括对捐献后活体肝脏捐献者生命质量影响因素进行分析的横断面研究或纵向研究。采用美国国立卫生研究院横断面研究和纵向研究质量评估工具(修订版)对纳入研究的方法学质量进行评价。结果共检索出6576篇文献,16篇符合纳入标准。将文献中影响活体肝脏捐献者生命质量的相关因素归纳为4类:社会人口学因素(性别、年龄、受教育程度、民族和婚姻状况)、捐献肝脏相关因素(捐献相关的住院时间或住院次数、受者结局、捐献后时长、捐献后并发症、捐献决定受支持情况、术前对个人健康担忧、捐献前存在捐献的矛盾心理、与受者关系)、健康状况相关因素(体质指数和捐献前有躯体症状)和心理社会因素(捐献前躯体和心理状态评分、家庭收入、焦虑、抑郁)。多数研究报道,老年、受者死亡、捐献肝脏后近期、捐献者经历术后并发症以及捐献者对自身健康的担忧是躯体功能的负面影响因素。女性捐献者、低教育水平、因捐献而住院时间长和/或住院次数多、受者预后不佳、捐献后近期、捐献肝脏前对自身健康担忧以及一级亲属和配偶捐献者是捐献后不良心理状态的负面预测因素。纳入研究中,仅有2篇文献考虑了社会功能的影响因素。结论活体肝脏捐献者的生命质量不仅受到捐献手术的影响,还包括心理和社会方面的因素。临床护理工作者可根据上述影响因素为捐献者制订有针对性的护理措施,以提高肝脏捐献者的生命质量。

Regulatory role of exosomes in colorectal cancer progression and potential as biomarkers

Colorectal cancer(CRC)remains an enormous challenge to human health worldwide.Unfortunately,the mechanism underlying CRC progression is not well understood.Mounting evidence has confirmed that exosomes play a vital role in CRC progression,which has attracted extensive attention among researchers.In addition to acting as messengers between CRC cells,exosomes also participate in the CRC immunomodulatory process and reshape immune function.As stable message carriers and liquid biopsy option under development,exosomes are promising biomarkers in the diagnosis or treatment of CRC.In this review we have described and analyzed the biogenesis and release of exosomes and current research on the role of exosomes in immune regulation and metastasis of CRC.Moreover,we have discussed candidate exosomal molecules as potential biomarkers to diagnose CRC,predict CRC progression,or determine CRC chemoresistance,and described the significance of exosomes in the immunotherapy of CRC.This review provides insight to further understand the role of exosomes in CRC progression and identify valuable biomarkers that facilitate the clinical management of CRC patients.

Washed microbiota transplantation stopped the deterioration of amyotrophic lateral sclerosis:The first case report and narrative review

Amyotrophic lateral sclerosis(ALS) is known as a progressive paralysis disorder characterized by degeneration of upper and lower motor neurons, and has an average survival time of three to five years. Growing evidence has suggested a bidirectional link between gut microbiota and neurodegeneration. Here we aimed to report one female case with ALS, who benefited from washed microbiota transplantation(WMT), an improved fecal microbiota transplantation(FMT), through a transendoscopic enteral tube during a 12-month follow-up. Notedly, the accidental scalp trauma the patient suffered later was treated with prescribed antibiotics that caused ALS deterioration. The subsequent rescue WMTs successfully stopped the progression of the disease with a quick improvement. The plateaus and reversals occurred during the whole course of WMT. The stool and blood samples from the first WMT to the last were collected for dynamic microbial and metabolomic analysis. We observed the microbial and metabolomic changing trend consistent with the disease status. This case report for the first time shows the direct clinical evidence on using WMT for treating ALS, indicating that WMT may be the novel treatment strategy for controlling this so-called incurable disease.

Analysis of risk factors associated with endoscopic retrograde cholangiopancreatography for patients with liver cirrhosis: a multicenter, retrospective, clinical study

Background:Endoscopic retrograde cholangiopancreatography(ERCP)is the endoscopic modality of choice for the treatment of biliary and pancreatic diseases.However,patients with cirrhosis,particularly those with decompensated cirrhosis,are believed to be at increased risk for complications associated with ERCP.There is a paucity of literature describing the outcomes of ERCP for patients with cirrhosis.This study aimed to investigate the outcomes of ERCP for cirrhosis patients,especially adverse events,and evaluated its safety and efficacy.Methods:We performed a multicenter,retrospective study of all patients at Beijing Friendship Hospital affiliated to Capital Medical University,Xijing Hospital affiliated to Air Force Military Medical University,Beijing Youan Hospital affiliated to Capital Medical University,and the Fifth Medical Center of the People’s Liberation Army General Hospital from June 2003 to August 2019.The adverse events of inpatient ERCP for patients with(n=182)and without liver cirrhosis(controls;n=385)were compared.Results:A total of 567 patients underwent ERCP between January 2003 and December 2019 were enrolled in this study.Compared to patients without cirrhosis,patients with cirrhosis were at higher risk for postoperative complications(odds ratio[OR],4.172;95%confidence interval[CI],1.232–7.031;P<0.001)such as postoperative pancreatitis(OR,2.026;95%CI,1.002–4.378;P=0.001)and cholangitis(OR,3.903;95%CI,1.001–10.038;P=0.036).The main indications for ERCP for patients with cirrhosis in this study included choledocholithiasis(101 cases;55.5%),benign bile duct strictures(46 cases;25.3%),and malignant bile duct strictures(28 cases;15.4%).Among them,23 patients(12.6%)underwent balloon dilation and 79 patients(43.4%)underwent sphincterotomy.Of the patients with cirrhosis,delayed bleeding occurred in ten patients(5.5%),postoperative pancreatitis occurred in 80 patients(44.0%),and postoperative cholangitis occurred in 25 patients(13.7%).An additional multivariate analysis showed that the total bilirubin(TBIL)level(OR,4.58;95%CI,2.37–6.70)and Child-Pugh score of C(OR,3.11;95%CI,1.04–5.37)were risk factors for postoperative complications in patients with cirrhosis.Conclusions:Compared with the general population of patients undergoing ERCP,patients with cirrhosis were more prone to postoperative pancreatitis and cholangitis.TBIL levels and Child-Pugh scores were risk factors for postoperative complications in patients with cirrhosis.

Effect of liver transplantation with primary hyperoxaluria type 1:Five case reports and review of literature

BACKGROUND Primary hyperoxaluria type 1(PH1)is a rare autosomal recessive disease stemming from a deficiency in liver-specific alanine-glyoxylate aminotransferase,resulting in increased endogenous oxalate deposition and end-stage renal disease.Organ transplantation is the only effective treatment.However,its approach and timing remain controversial.CASE SUMMARY We retrospectively analyzed 5 patients diagnosed with PH1 from the Liver Transplant Center of the Beijing Friendship Hospital from March 2017 to December 2020.Our cohort included 4 males and 1 female.The median age at onset was 4.0 years(range:1.0-5.0),age at diagnosis was 12.2 years(range:6.7-23.5),age at liver transplantation(LT)was 12.2 years(range:7.0-25.1),and the follow-up time was 26.3 mo(range:12.8-40.1).All patients had delayed diagnosis,and 3patients had progressed to end-stage renal disease by the time they were diagnosed.Two patients received preemptive LT;their estimated glomerular filtration rate was maintained at>120 mL/min/1.73 m2,indicating a better prognosis.Three patients received sequential liver and kidney transplantation.After transplantation,serum and urinary oxalate decreased,and liver function recovered.At the last follow-up,the estimated glomerular filtration rates of the latter 3 patients were 179,52 and 21 mL/min/1.73 m2.CONCLUSION Different transplantation strategies should be adopted for patients based on their renal function stage.Preemptive-LT offers a good therapeutic approach for PH1.