Prediabetes: An overlooked risk factor for major adverse cardiac and cerebrovascular events in atrial fibrillation patients

BACKGROUND Prediabetes is a well-established risk factor for major adverse cardiac and cerebrovascular events(MACCE).However,the relationship between prediabetes and MACCE in atrial fibrillation(AF)patients has not been extensively studied.Therefore,this study aimed to establish a link between prediabetes and MACCE in AF patients.AIM To investigate a link between prediabetes and MACCE in AF patients.METHODS We used the National Inpatient Sample(2019)and relevant ICD-10 CM codes to identify hospitalizations with AF and categorized them into groups with and without prediabetes,excluding diabetics.The primary outcome was MACCE(all-cause inpatient mortality,cardiac arrest including ventricular fibrillation,and stroke)in AF-related hospitalizations.RESULTS Of the 2965875 AF-related hospitalizations for MACCE,47505(1.6%)were among patients with prediabetes.The prediabetes cohort was relatively younger(median 75 vs 78 years),and often consisted of males(56.3%vs 51.4%),blacks(9.8%vs 7.9%),Hispanics(7.3%vs 4.3%),and Asians(4.7%vs 1.6%)than the non-prediabetic cohort(P<0.001).The prediabetes group had significantly higher rates of hypertension,hyperlipidemia,smoking,obesity,drug abuse,prior myocardial infarction,peripheral vascular disease,and hyperthyroidism(all P<0.05).The prediabetes cohort was often discharged routinely(51.1%vs 41.1%),but more frequently required home health care(23.6%vs 21.0%)and had higher costs.After adjusting for baseline characteristics or comorbidities,the prediabetes cohort with AF admissions showed a higher rate and significantly higher odds of MACCE compared to the non-prediabetic cohort[18.6%vs 14.7%,odds ratio(OR)1.34,95%confidence interval 1.26-1.42,P<0.001].On subgroup analyses,males had a stronger association(aOR 1.43)compared to females(aOR 1.22),whereas on the race-wise comparison,Hispanics(aOR 1.43)and Asians(aOR 1.36)had a stronger association with MACCE with prediabetes vs whites(aOR 1.33)and blacks(aOR 1.21).CONCLUSION This population-based study found a significant association between prediabetes and MACCE in AF patients.Therefore,there is a need for further research to actively screen and manage prediabetes in AF to prevent MACCE.

Impact of body mass index on adverse kidney events in diabetes mellitus patients: A systematic-review and meta-analysis

BACKGROUND The incidence of chronic kidney disease among patients with diabetes mellitus(DM)remains a global concern.Long-term obesity is known to possibly influence the development of type 2 diabetes mellitus.However,no previous meta-analysis has assessed the effects of body mass index(BMI)on adverse kidney events in patients with DM.AIM To determine the impact of BMI on adverse kidney events in patients with DM.METHODS A systematic literature search was performed on the PubMed,ISI Web of Science,Scopus,Ovid,Google Scholar,EMBASE,and BMJ databases.We included trials with the following characteristics:(1)Type of study:Prospective,retrospective,randomized,and non-randomized in design;(2)participants:Restricted to patients with DM aged≥18 years;(3)intervention:No intervention;and(4)kidney adverse events:Onset of diabetic kidney disease[estimated glomerular filtration rate(eGFR)of<60 mL/min/1.73 m2 and/or microalbuminuria value of≥30 mg/g Cr],serum creatinine increase of more than double the baseline or end-stage renal disease(eGFR<15 mL/min/1.73 m2 or dialysis),or death.RESULTS Overall,11 studies involving 801 patients with DM were included.High BMI(≥25 kg/m2)was significantly associated with higher blood pressure(BP)[systolic BP by 0.20,95%confidence interval(CI):0.15–0.25,P<0.00001;diastolic BP by 0.21 mmHg,95%CI:0.04–0.37,P=0.010],serum albumin,triglycerides[standard mean difference(SMD)=0.35,95%CI:0.29–0.41,P<0.00001],low-density lipoprotein(SMD=0.12,95%CI:0.04–0.20,P=0.030),and lower high-density lipoprotein(SMD=–0.36,95%CI:–0.51 to–0.21,P<0.00001)in patients with DM compared with those with low BMIs(<25 kg/m2).Our analysis showed that high BMI was associated with a higher risk ratio of adverse kidney events than low BMI(RR:1.22,95%CI:1.01–1.43,P=0.036).CONCLUSION The present analysis suggested that high BMI was a risk factor for adverse kidney events in patients with DM.

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

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

Performance of the EDACS-ADP incorporating high-sensitivity troponin assay:Do components of major adverse cardiac events matter?

BACKGROUND:The accelerated diagnostic protocol(ADP)using the Emergency Department Assessment of Chest pain Score(EDACS-ADP),a tool to identify patients at low risk of a major adverse cardiac event(MACE)among patients presenting with chest pain to the emergency department,was developed using a contemporary troponin assay.This study was performed to validate and compare the performance of the EDACS-ADP incorporating high-sensitivity cardiac troponin I between patients who had a 30-day MACE with and without unstable angina(MACE I and II,respectively).METHODS:A single-center prospective observational study of adult patients presenting with chest pain suggestive of acute coronary syndrome was performed.The performance of EDACS-ADP in predicting MACE was assessed by calculating the sensitivity and negative predictive value.RESULTS:Of the 1,304 patients prospectively enrolled,399(30.6%;95%confidence interval[95%CI]:27.7%–33.8%)were considered low-risk using the EDACS-ADP.Among them,the rates of MACE I and II were 1.3%(5/399)and 1.0%(4/399),respectively.The EDACS-ADP showed sensitivities and negative predictive values of 98.8%(95%CI:97.2%–99.6%)and 98.7%(95%CI:97.0%–99.5%)for MACE I and 98.7%(95%CI:96.8%–99.7%)and 99.0%(95%CI:97.4%–99.6%)for MACE II,respectively.CONCLUSION:EDACS-ADP could help identify patients as safe for early discharge.However,when unstable angina was added to the outcome,the 30-day MACE rate among the designated lowrisk patients remained above the level acceptable for early discharge without further evaluation.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio:Markers predicting immune-checkpoint inhibitor efficacy and immune-related adverse events

We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting irAEs.Furthermore,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers alone.NLR and PLR are promising markers for clinical applications.Forthcoming models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite model.Furthermore,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.

Predictive Effect of CA125 on Adverse Cardiovascular Events in Patients with Chronic Heart Failure

Objective: To study the expression of CA125 in the serum of patients with CHF and the relationship between CA125 level and the occurrence of adverse cardiovascular events. Methods: The clinical data of 132 patients with CHF admitted to Shizuishan Second People’s Hospital from January 2023 to December 2023 were collected and divided into heart function II group, heart function III group, heart function IV group according to cardiac function. 44 healthy subjects who underwent physical examination during the same period were selected as the control group. The clinical data of CA125, NT-proBNP, echocardiography and other clinical data of the four groups were compared, and the incidence of major adverse cardiovascular events was followed up for 12 months. Results: Compared with the control group, the CA125 level in the CHF group was significantly increased (P Conclusion: Serum CA125 level is related to the cardiac function level in CHF patients and increases with the deterioration of cardiac function. The increase of the index is related to the mortality rate and re-hospitalization rate, suggesting that CA125 can be used as an indicator to reflect the severity of heart failure and prognosis monitoring.

Value of improved nursing measures and enhanced nursing management to reduce the occurrence of adverse events in pediatric infusion

BACKGROUND Intravenous infusion is a common method of drug administration in clinical practice.Errors in any aspect of the infusion process,from the verification of medical orders,preparation of the drug solution,to infusion by nursing staff,may cause adverse infusion events.AIM To analyzed the value of improving nursing measures and enhancing nursing management to reduce the occurrence of adverse events in pediatric infusion.METHODS The clinical data of 130 children who received an infusion in the pediatric department of our hospital from May 2020 to May 2021 were analyzed and divided into two groups according to the differences in nursing measures and nursing management:65 patients in the control group received conventional nursing and nursing management interventions,while 65 patients in the observation group received improved nursing measure interventions and enhanced nursing management.The occurrence of adverse events,compliance of children,satisfaction of children’s families,and complaints regarding the transfusion treatment were recorded in both groups.RESULTS The incidence of fluid extravasation and infusion set dislodgement in the observation group were 3.08%and 1.54%,respectively,which were significantly lower than 12.31%and 13.85%in the control group(P<0.05),while repeated punctures and medication addition errors in the observation group were 3.08%and 0.00%,respectively,which were lower than 9.23%and 3.08%in the control group,but there was no significant difference(P>0.05).The compliance rate of children in the observation group was 98.46%(64/65),which was significantly higher than 87.69%(57/65)in the control group,and the satisfaction rate of children’s families was 96.92%(63/65),which was significantly higher than 86.15%(56/65)in the control group(P<0.05).The observation group did not receive any complaints from the child’s family,whereas the control group received four complaints,two of which were due to the crying of the child caused by repeated punctures,one due to the poor attitude of the nurse,and one due to medication addition errors,with a cumulative complaint rate of 6.15%.The cumulative complaint rate of the observation group was significantly lower than that of the control group(P<0.05).CONCLUSION Improving nursing measures and enhancing nursing management can reduce the incidence of fluid extravasation and infusion set dislodgement in pediatric patients,improve children’s compliance and satisfaction of their families,and reduce family complaints.

Contemporary nationwide trends in major adverse cardiovascular events in young cannabis users without concomitant tobacco,alcohol,cocaine use

BACKGROUND Cannabis use has increased among young individuals in recent years.Although dependent cannabis use disorder(CUD)has been associated with various cardiac events,its effects on young adults without concurrent substance use remain understudied.AIM To examine trends in hospitalizations for major adverse cardiac and cerebrovascular events(MACCE)in this cohort.METHODSWe used the National Inpatient Sample(2016-2019)to identify hospitalized young individuals(18-44 years),excluding those with concurrent substance usage(tobacco,alcohol,and cocaine).They were divided into CUD+and CUD-.Using International Classification of Diseases-10 codes,we examined the trends in MACCE hospitalizations,including all-cause mortality(ACM),acute myocardial infarction(AMI),cardiac arrest(CA),and acuteischemic stroke(AIS).RESULTSOf 27.4 million hospitalizations among young adults without concurrent substance abuse,4.2%(1.1 million)hadco-existent CUD.In CUD+group,hospitalization rates for MACCE(1.71%vs 1.35%),AMI(0.86%vs 0.54%),CA(0.27%vs 0.24%),and AIS(0.49%vs 0.35%)were higher than in CUD-group(P<0.001).However,rate of ACMhospitalizations was lower in CUD+group(0.30%vs 0.44%).From 2016 to 2019,CUD+group experienced arelative rise of 5%in MACCE and 20%in AMI hospitalizations,compared to 22%and 36%increases in CUDgroup(P<0.05).The CUD+group had a 13%relative decrease in ACM hospitalizations,compared to a 10%relative rise in CUD-group(P<0.05).However,when adjusted for confounders,MACCE odds among CUD+cohort remain comparable between 2016 and 2019.CONCLUSIONThe CUD+group had higher rates of MACCE,but the rising trends were more apparent in the CUD-group overtime.Interestingly,the CUD+group had lower ACM rates than the CUD-group.

Adverse Events following AstraZeneca COVID-19 Vaccination: A Case Study in Abidjan, Côte d’Ivoire

Introduction: Pharmaceutical companies have boosted vaccine production following the global COVID-19 pandemic. In Côte d’Ivoire, the first vaccination campaign with the AstraZeneca vaccine began on March 1, 2021, as part of the Covax program. Despite the positive benefit/risk balance, the adverse effects of vaccination should not be minimized. Objective: To identify adverse events of AstraZeneca’s COVID-19 vaccination for better management. Materials and Methods: This is a case of a 57-year-old obese (BMI = 39 kg/m2) female health care worker who experienced adverse events in March 2021 after the second dose of AstraZeneca vaccine administered 4 weeks apart. These were subject to mandatory case reporting. Results: Major post-vaccination events occurred in a noisy systemic picture with parameters showing significant disturbances. Biological surveillance remains costly and makes the accountability of the vaccine complex. Conclusion: Vaccination remains the ultimate weapon in the fight against endemic diseases but should not overshadow the reporting of adverse events.

Biomarkers associated with immune-related adverse events induced by immune checkpoint inhibitors

Immune checkpoint inhibitors(ICIs)constitute a pivotal class of immunotherapeutic drugs in cancer treatment.However,their widespread clinical application has led to a notable surge in immune-related adverse events(irAEs),significantly affecting the efficacy and survival rates of patients undergoing ICI therapy.While conventional hematological and imaging tests are adept at detecting organ-specific toxicities,distinguishing adverse reactions from those induced by viruses,bacteria,or immune diseases remains a formidable challenge.Consequently,there exists an urgent imperative for reliable biomarkers capable of accurately predicting or diagnosing irAEs.Thus,a thorough review of existing studies on irAEs biomarkers is indispensable.Our review commences by providing a succinct over-view of major irAEs,followed by a comprehensive summary of irAEs biomarkers across various dimensions.Furthermore,we delve into innovative methodologies such as machine learning,single-cell RNA sequencing,multiomics analysis,and gut microbiota profiling to identify novel,robust biomarkers that can facilitate precise irAEs diagnosis or prediction.Lastly,this review furnishes a concise exposition of irAEs mechanisms to augment understanding of irAEs prediction,diagnosis,and treatment strategies.

Adverse events related to colonoscopy: Global trends and future challenges

Colonoscopy is a widely used method for diagnosing and treating colonic disease. The number of colonoscopies is increasing worldwide, and concerns about associated adverse events are growing. Large-scale studies using big data for post-colonoscopy complications have been reported. A colon perforation is a severe complication with a relatively high mortality rate. The perforation rate, as reported in large studies(≥ 50,000 colonoscopies) published since 2000, ranges from 0.005-0.085%. The trend in the overall perforation rate in the past 15 years has not changed significantly. Bleeding is a more common adverse event than perforation. Recent large studies(≥ 50,000 colonoscopies) have reported postcolonoscopy bleeding occurring in 0.001-0.687% of cases. Most studies about adverse events related to colonoscopy were performed in the West, and relatively few studies have been conducted in the East. The incidence of post-colonoscopy complications increases in elderly patients or patients with inflammatory bowel diseases. It is important to use a unified definition and refined data to overcome the limitations of previous studies. In addition, a structured training program for endoscopists and a systematic national management program are needed to reduce post-colonoscopy complications. In this review, we discuss the current trends in colonoscopy related to adverse events, as well as the challenges to be addressed through future research.

Adverse events with bismuth salts for Helicobacter pylori eradication:Systematic review and meta-analysis

AIM： To assess the safety of bismuth used in Helicobacter pylori （H pylorl） eradication therapy regimens. METHODS： We conducted a systematic review and meta-analysis. MEDLINE and EMBASE were searched （up to October 2007） to identify randomised controlled tri- als comparing bismuth with placebo or no treatment, or bismuth salts in combination with antibiotics as part of eradication therapy with the same dose and duration of antibiotics alone or, in combination, with acid suppresion. Total numbers of adverse events were recorded. Data were pooled and expressed as relative risks with 95% confidence intervals （CI）.RESULTS： We identified 35 randomised controlled trials containing 4763 patients. There were no serious adverse events occurring with bismuth therapy. There was no statistically significant difference detected in total adverse events with bismuth rrelative risk （RR） = 1.01; 95% CI： 0.87-1.16], specific individual adverse events, with the exception of dark stools （RR = 5.06; 95% CI： 1.59-16.12）, or adverse events leading to withdrawal of therapy （RR = 0.86; 95% CI： 0.54-1.37）. CONCLUSION： Bismuth for the treatment of H py/ori is safe and well-tolerated. The only adverse event occurring significantly more commonly was dark stools.

Severe adverse events during antiviral therapy in hepatitis C virus cirrhotic patients: A systematic review

AIM: To identify severe adverse events (SAEs) leading to treatment discontinuation that occur during antiviral therapy in hepatitis C virus (HCV)-infected cirrhotic patients. METHODS: We identified all the articles published prior to December 2011 in the PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases that presented these data in cirrhotic patients. These studies evaluated the rate of SAEs leading to discontinuation of standard care treatment: Pegylated interferon (PegIFN) alpha 2a (135-180 μg/wk) or PegIFN alpha 2b (1 or 1.5 μg/kg per week) and ribavirin (800-1200 mg/d). Patients with genotype 1 + 4 underwent treatment for 48 wk, whereas those with genotypes 2 + 3 were treated for 24 wk.RESULTS: We included 17 papers in this review, comprising of 1133 patients. Treatment was discontinued due to SAEs in 14.5% of the patients. The most common SAEs were: severe thrombocytopenia and/or neutropenia (23.2%), psychiatric disorders (15.5%), decompensation of liver cirrhosis (12.1%) and severe anemia (11.2%). The proportion of patients who needed to discontinue their therapy due to SAEs was significantly higher in patients with Child-Pugh class B and Cvs those with Child-Pugh class A: 22%vs 11.4% (P = 0.003). A similar discontinuation rate was found in cirrhotic patients treated with PegIFN alpha 2a and those treated with PegIFN alpha 2b, in combination with ribavirin: 14.2%vs 13.7% (P = 0.96). The overall sustained virological response rate in cirrhotic patients was 37% (95%CI: 33.5-43.1) but was significantly lower in patients with genotype 1 + 4 than in those with genotype 2 + 3: 20.5% (95%CI: 17.9-24.8) vs 56.5% (95%CI: 51.5-63.2), (P < 0.0001). CONCLUSION: Fourteen point five percent of HCV cirrhotic patients treated with PegIFN and ribavirin needed early discontinuation of therapy due to SAEs, the most common cause being hematological disorders.

Adverse Respiratory Events Increase Post-anesthesia Care Unit Stay in China:A 2-year Retrospective Matched Cohort Study

Despite growing attention to patients,safety worldwide,no data were available on the impact of adverse respiratory events(AREs)on post-anesthesia care and post-operation care in China.This study evaluated the occurrence of AREs,the impact of AREs on length of stay(LOS)in post-anesthesia care unit(PACU)and postoperative time in hospital,and PACU cost and in patient healthcare costs.A retrospective,matched-cohort study was conducted by prospectively collecting the data of 159 AREs in PACU during 2016-2017 in an university hospital in China.Records were reviewed by pre-trained,qualified nurses and/or anesthesiologists.The incidence and the impact of AREs were analyzed.The LOS in PACU and postoperative time in hospital and the costs in PACU and inpatient healthcare costs were also obtained.Results showed that there were 253 AREs involving 156 patients.Hypoxia(n=141,55.73%)and respiratory depression(n=70,27.67%)were the most common AREs.Measurement data including body mass index(BMI)(22.85±4.36 vs.22.32±3.83),duration of procedure(138.47±77.33 min vs.137.44±72.33 min),duration of anesthesia(176.35±82.66 min vs.174.61±78.08 min),LOS(16.53±10.65 days vs.16.57±9.56 days),inpatient healthcare costs($9465.57±9416.33 vs.$8166.51±5762.01),and postoperative LOS(11.26±8.77 days vs.11.9±8.30 days)showed no significant differences between ARE and matched groups(P<0.05).Duration(81.65±54.79 min vs.38.89±26.09 min)and costs($31.99±17.80 vs.$18.72±8.39)in PACU were significantly different in ARE group from those in matched group(P<0.001).Proportion of patients with prolonged stay in PACU was significantly higher in ARE group than in matched group(18.59%vs.1.28%),with an odds ratio(after matching)of 17.58(95%CI=4.11 to 75.10;P<0.001).The AREs that occurred during the immediate postoperative period in PACU increased the incidence rate of prolonged stay,delayed the PACU stay,and increased the costs in PACU,resulting in the need of higher levels of postoperative care than anticipated,but the postoperative LOS and inpatient healthcare costs were unchanged.

Endoscopic retrograde cholangiopancreatography in cirrhosis-a systematic review and meta-analysis focused on adverse events

AIM To investigate indications and outcomes of endoscopic retrograde cholangiopancreatography(ERCP) in cirrhotics, especially adverse events. Patients with cirrhosis undergoing ERCP are believed to have increased risk. However, there is a paucity of literature describing the indications and outcomes of ERCP procedures in patients with cirrhosis, especially focusing on adverse events.METHODS We performed a systematic appraisal of major literature databases, including PubMed and EMBASE, with a manual search of literature from their inception until April 2017.RESULTS A total of 6,505 patients from 15 studies were analyzed(male ratio 59%, mean age 59 years), 11% with alcoholic and 89% with non-alcoholic cirrhosis, with 56.2% Child-Pugh class A, and 43.8% class B or C. Indications for ERCP included choledocholithiasis 60.9%, biliary strictures 26.2%, gallstone pancreatitis 21.1% and cholangitis 15.5%. Types of interventions included endoscopic sphincterotomy 52.7%, biliary stenting 16.7% and biliary dilation 4.6%. Individual adverse events included hemorrhage in 4.58%(95%CI: 2.77-6.75%, I^2 = 85.9%), post-ERCP pancreatitis(PEP) in 3.68%(95%CI: 1.83-6.00%, I^2 = 89.5%), cholangitis in 1.93%(95%CI: 0.63-3.71%, I^2 = 87.1%) and perforation in 0.00%(95%CI: 0.00-0.23%, I^2 = 37.8%). Six studies were used for comparison of ERCPrelated complications in cirrhosis vs non-cirrhosis, which showed higher overall rates of complications in cirrhosis patients with pooled OR of 1.63(95%CI: 1.27-2.09, I2 = 65%): higher rates of hemorrhage with OR of 2.05(95%CI: 1.62-2.58, I^2 = 2.1%) and PEP with OR of 1.33(95%CI: 1.04-1.70, I2=65%), but similar cholangitis rates with OR of 1.23(95%CI: 0.67-2.26, I^2 = 44.3%).CONCLUSION There is an overall higher rate of adverse events related to ERCP in patients with cirrhosis, especially hemorrhage and PEP. A thorough risk/benefit assessment should be performed prior to undertaking ERCP in patients with cirrhosis.

rate of adverse events of gastroduodenal snare polypectomy for non-flat polyp is low: A prospective and multicenter study

AIM To evaluate the rate of adverse events(AEs) during consecutive gastric and duodenal polypectomies in several Spanish centers. METHODS Polypectomies of protruded gastric or duodenal polyps ≥ 5 mm using hot snare were prospectively included. Prophylactic measures of hemorrhage were allowed in predefined cases. AEs were defined and graded according to the lexicon recommended by the American Society for Gastrointestinal Endoscopy. Patients were followed for 48 h, one week and 1 mo after theprocedure. RESULTS308 patients were included and a single polypectomy was performed in 205. Only 36(11.7%) were on prior anticoagulant therapy. Mean polyp size was 15 ± 8.9 mm(5-60) and in 294 cases(95.4%) were located in the stomach. Hemorrhage prophylaxis was performed in 219(71.1%) patients. Nine patients presented AEs(2.9%), and 6 of them were bleeding(n = 6, 1.9%)(in 5 out of 6 AE, different types of endoscopic treatment were performed). Other 24 hemorrhagic episodes could be managed without any change in the outcome of the endoscopy and, consequently, were considered incidents. We did not find any independent risk factor of bleeding.CONCLUSION Gastroduodenal polypectomy using prophylactic measures has a rate of AEs small enough to consider this procedure a safe and effective method for polyp resection independently of the polyp size and location.

Genetic associations with adverse events from anti-tumor necrosis factor therapy in inflammatory bowel disease patients

AIM To study the type and frequency of adverse events associated with anti-tumor necrosis factor(TNF)therapy and evaluate for any serologic and genetic associations.METHODS This study was a retrospective review of patients attending the inflammatory bowel disease(IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified via chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium Immunochipv1 array per manufacturer's protocol. SNPs underwent methodological review and were evaluated using several SNP statistic parameters to ensure optimal allele-calling. Standard and rigorous QC criteria were applied to the genetic data, which was generated using immunochip. Genetic association was assessed by logistic regression after correcting for population structure.RESULTS Altogether we identified 1258 IBD subjects exposed to anti-TNF agents in whom Immunochip data were available. 269/1258 patients(21%) were found to have adverse events to an anti-TNF-α agent that required the therapy to be discontinued. 25% of women compared to 17% of men experienced an adverse event. All adverse events resolved after discontinuing the antiTNF agent. In total: n = 66(5%) infusion reactions; n = 49(4%) allergic/serum sickness reactions; n = 19(1.5%) lupus-like reactions, n = 52(4%) rash, n = 18(1.4%) infections. In Crohn's disease, Ig A ASCA(P = 0.04) and Ig G-ASCA(P = 0.02) levels were also lower in patients with any adverse events, and anti-I2 level in ulcerative colitis was significantly associated with infusion reactions(P = 0.008). The logistic regression/human annotation and network analyses performed on the Immunochip data implicated the following five signaling pathways: JAK-STAT(Janus Kinase-signal transducer and activator of transcription), measles, IBD, cytokine-cytokine receptor interaction, and toxoplasmosis for any adverse event. CONCLUSION Our study shows 1 in 5 IBD patients experience an adverse event to anti-TNF therapy with novel serologic, genetic, and pathways associations.

Postoperative biliary adverse events following orthotopic liver transplantation: Assessment with magnetic resonance cholangiography

Biliary adverse events following orthotopic liver transplantation (OLT) are relatively common and continue to be serious causes of morbidity, mortality, and transplant dysfunction or failure. The development of these adverse events is heavily influenced by the type of anastomosis during surgery. The low specificity of clinical and biologic findings makes the diagnosis challenging. Moreover, direct cholangiographic procedures such as endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography present an inadmissible rate of adverse events to be utilized in clinically low suspected patients. Magnetic resonance (MR) maging with MR cholangiopancreatography is crucial in assessing abnormalities in the biliary system after liver surgery, including liver transplant. MR cholangiopancreatography is a safe, rapid, non-invasive, and effective diagnostic procedure for the evaluation of biliary adverse events after liver transplantation, since it plays an increasingly important role in the diagnosis and management of these events. On the basis of a recent systematic review of the literature the summary estimates of sensitivity and specificity of MR cholangiopancreatography for diagnosis of biliary adverse events following OLT were 0.95 and 0.92, respectively. It can provide a non-invasive method of imaging surgical reconstruction of the biliary anastomoses as well as adverse events including anastomotic and non-anastomotic strictures, biliary lithiasis and sphincter of Oddi dysfunction in liver transplant recipients. Nevertheless, conventional T2-weighted MR cholangiography can be implemented with T1-weighted contrast-enhanced MR cholangiography using hepatobiliary contrast agents (in particular using Gd-EOB-DTPA) in order to improve the diagnostic accuracy in the adverse events&#x02019; detection such as bile leakage and strictures, especially in selected patients with biliary-enteric anastomosis.

Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events

Objective:We aimed to retrospectively analyze the toxicity profiles and predictors of immune-related adverse events(irAEs)as well as the correlation between irAEs and the clinical efficacy of multi-type immune checkpoint inhibitors(ICIs)in patients with advanced pan-cancer in a real-world setting.Methods:We retrospectively analyzed data from 105 patients with advanced pan-cancer treated with multi-type ICIs at the First Hospital of Jilin University between January 1,2016 and August 1,2020.We used logistic regression analyses to investigate the associations of irAEs with clinical baseline characteristics,blood count parameters,and biochemical indicators during treatment.Receiver operating characteristic curves were used to determine cutoff values for parameters and area under the curve values.Kaplan–Meier and Cox multivariate regression analyses were performed to estimate the relationships of baseline characteristics and irAEs with progression-free survival(PFS)and overall survival(OS).Results:A lower relative lymphocyte count(cutoff=28.5%),higher albumin level(cutoff=39.05 g/L),and higher absolute eosinophil count(AEC)(cutoff=0.175×10^(9)/L)were significantly associated with the occurrence of irAEs,among which a higher AEC(cutoff=0.205×10^(9)/L)was strongly associated with skin-related irAEs[odds ratios(ORs)=0.163,P=0.004].Moreover,a higher lactate dehydrogenase level(cutoff=237.5 U/L)was an independent predictor of irAEs of grade≥3(OR=0.083,P=0.023).In immune cell subgroup analysis,a lower absolute count of CD8+CD28−suppressor T cells(OR=0.806;95%confidence interval:0.643–1.011;P=0.062),which are regulatory T lymphocytes,was associated with the occurrence of irAEs,although the difference was not statistically significant.Furthermore,a higher percentage of CD19+B cells was associated with the occurrence of irAEs of grade≥3(P=0.02)and grade≥2(P=0.051).In addition,patients with any grade of irAE had a significantly high PFS(8.37 vs.3.77 months,hazard ratios(HR)=2.02,P=0.0038)and OS(24.77 vs.13.83 months,HR=1.84;P=0.024).Conclusions:This retrospective study reports clinical profile data for irAEs in unselected patients in a real-world setting and explored some parameters that may be potential predictive markers of the occurrence,type,or grade of irAEs in clinical practice.Evidence of a correlation between safety and efficacy may facilitate a complete assessment of the risk-benefit ratio for patients treated with ICIs.

Clinical predictors of thiopurine-related adverse events in Crohn's disease

AIM: To determine the incidence and predictors of thiopurine-related adverse events. METHODS: Subjects with Crohn's disease who were followed in the Alberta Inflammatory Bowel Disease Consortium patient database registry were identified. Retrospective chart review was conducted between August 5th, 2010 and June 1st, 2012. We collected data on: age at diagnosis; sex; disease location and behaviour at time of prescribing thiopurine; perianal fistulising disease at or prior to thiopurine prescription; smoking status at time of thiopurine prescription, use of corticosteroid within 6 mo of diagnosis; dosage, age at onset, and cessation of 5-aminosalicyclic acid(5-ASA); anti-tumour necrosis factor medication exposure and intestinal resection before thiopurine prescription. The primary outcome of interest was the first adverse event that led to discontinuation of the first thiopurine medication used. Logistic regression models were used to associate clinical characteristics with outcomes after adjusting for potential confounders. Risk estimates were presented as odds ratios(OR) with 95% CI. Effect modification by age and sex were explored.RESULTS: Our cohort had a median follow-up duration of 5.8 years [interquartile range(IQR 25th-75th) 2.7-9.1]. Thiopurine therapy was discontinued in 31.3% of patients because of: hypersensitivity reactions(7.1%), acute pancreatitis(6.2%), gastrointestinal intolerance(5.4%), leucopenia(3.7%), hepatotoxicity(3.4%), infection(1.1%) and other reasons(4.3%). A higher incidence of thiopurine withdrawal was observed in patients over the age of 40(39.4%, P = 0.007). A sexby-age interaction(P = 0.04) was observed. Females older than 40 years of age had an increased risk of thiopurine discontinuation due to an adverse event(age above 40 vs age below 40, adjusted OR = 2.8; 95%CI: 1.4-5.6). In contrast, age did not influence thiopurine withdrawal in males(age above 40 vs below 40, adjusted OR = 0.9; 95%CI: 0.4-2.1). Other clinical variables(disease location and phenotype, perianal disease, smoking history, history of intestinal resection and prior 5-ASA or corticosteroid use) were not associated with an increased risk an adverse event leading to therapy cessation. CONCLUSION: Thiopurine withdrawal due to adverse events is commoner in women over the age of 40 at prescription. These findings need to be replicated in other cohorts.