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.

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.

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.

Sex and racial disparities in non-alcoholic fatty liver disease-related cardiovascular events: National inpatient sample analysis (2019)

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases cardiovascular disease(CVD)risk irrespective of other risk factors.However,large-scale cardiovascular sex and race differences are poorly understood.AIM To investigate the relationship between NAFLD and major cardiovascular and cerebrovascular events(MACCE)in subgroups using a nationally representative United States inpatient sample.METHODS We examined National Inpatient Sample(2019)to identify adult hospitalizations with NAFLD by age,sex,and race using ICD-10-CM codes.Clinical and demographic characteristics,comorbidities,and MACCE-related mortality,acute myocardial infarction(AMI),cardiac arrest,and stroke were compared in NAFLD cohorts by sex and race.Multivariable regression analyses were adjusted for sociodemographic characteristics,hospitalization features,and comorbidities.RESULTS We examined 409130 hospitalizations[median 55(IQR 43-66)years]with NFALD.NAFLD was more common in females(1.2%),Hispanics(2%),and Native Americans(1.9%)than whites.Females often reported non-elective admissions,Medicare enrolment,the median age of 55(IQR 42-67),and poor income.Females had higher obesity and uncomplicated diabetes but lower hypertension,hyperlipidemia,and complicated diabetes than males.Hispanics had a median age of 48(IQR 37-60),were Medicaid enrollees,and had non-elective admissions.Hispanics had greater diabetes and obesity rates than whites but lower hypertension and hyperlipidemia.MACCE,all-cause mortality,AMI,cardiac arrest,and stroke were all greater in elderly individuals(P<0.001).MACCE,AMI,and cardiac arrest were more common in men(P<0.001).Native Americans(aOR 1.64)and Asian Pacific Islanders(aOR 1.18)had higher all-cause death risks than whites.CONCLUSION Increasing age and male sex link NAFLD with adverse MACCE outcomes;Native Americans and Asian Pacific Islanders face higher mortality,highlighting a need for tailored interventions and care.

Elevated cardiovascular risk and acute events in hospitalized colon cancer survivors:A decade-apart study of two nationwide cohorts

BACKGROUND Over the years,strides in colon cancer detection and treatment have boosted survival rates;yet,post-colon cancer survival entails cardiovascular disease(CVD)risks.Research on CVD risks and acute cardiovascular events in colorectal cancer survivors has been limited.AIM To compare the CVD risk and adverse cardiovascular outcomes in current colon cancer survivors compared to a decade ago.METHODS We analyzed 2007 and 2017 hospitalization data from the National Inpatient Sample,studying two colon cancer survivor groups for CVD risk factors,mortality rates,and major adverse events like pulmonary embolism,arrhythmia,cardiac arrest,and stroke,adjusting for confounders via multivariable regression analysis.RESULTS Of total colon cancer survivors hospitalized in 2007(n=177542)and 2017(n=178325),the 2017 cohort often consisted of younger(76 vs 77 years),male,African-American,and Hispanic patients admitted non-electively vs the 2007 cohort.Furthermore,the 2017 cohort had higher rates of smoking,alcohol abuse,drug abuse,coagulopathy,liver disease,weight loss,and renal failure.Patients in the 2017 cohort also had higher rates of cardiovascular comorbidities,including hypertension,hyperlipidemia,diabetes,obesity,peripheral vascular disease,congestive heart failure,and at least one traditional CVD(P<0.001)vs the 2007 cohort.On adjusted multivariable analysis,the 2017 cohort had a significantly higher risk of pulmonary embolism(PE)(OR:1.47,95%CI:1.37-1.48),arrhythmia(OR:1.41,95%CI:1.38-1.43),atrial fibrillation/flutter(OR:1.61,95%CI:1.58-1.64),cardiac arrest including ventricular tachyarrhythmia(OR:1.63,95%CI:1.46-1.82),and stroke(OR:1.28,95%CI:1.22-1.34)with comparable all-cause mortality and fewer routine discharges(48.4%vs 55.0%)(P<0.001)vs the 2007 cohort.CONCLUSION Colon cancer survivors hospitalized 10 years apart in the United States showed an increased CVD risk with an increased risk of acute cardiovascular events(stroke 28%,PE 47%,arrhythmia 41%,and cardiac arrest 63%).It is vital to regularly screen colon cancer survivors with concomitant CVD risk factors to curtail long-term cardiovascular complications.

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.

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.

Correlation between heart rate variables and the incidence of cardiovascular adverse events in patients with heart failure

Background Chronic heart failure(CHF)is the end-stage manifestation and main cause of death of cardiovascular system diseases.Ventricular arrhythmia is a common complication,which can increase myocardial oxygen consumption,aggravate the disease,and even cause sudden death due to malignant arrhythmia.As a quantitative method to evaluate cardiac autonomic nervous function,heart rate variability is non-invasive and reproducible,and can quantify the risk associated with various cardiac and non-cardiac diseases.The purpose of this study was to analyze the correlation between heart rate variability and the incidence of cardiovascular adverse events in patients with heart failure.Methods 80 patients with heart failure who were treated in our hospital from May 2020 to May 2022 were selected as the study objects.After 3 months of follow-up,patients were divided into occurrence group(n=44)and nonoccurrence group(n=36)according to the occurrence of adverse cardiovascular events(angina pectoris,myocardial infarction,arrhythmia).The index of heart rate variability and the indicators of cardiac function in patients with heart failure was analyzed by one-way analysis of variance(ANOVA).The Key indicators of heart rate variability include standard deviation of normal RR interval(SDNN),mean standard deviation of consecutive 5-minute heartbeat interval(SDANN),square root of mean square of difference between adjacent heartbeat intervals(RMSSD),and percentage of RR intervals differing more than 50 ms from the preceding one(PNN50).The indicators of cardiac function include the New York Heart Association(NYHA)functional classification,left ventricular ejection fraction(LVEF),brain natriuretic peptide(BNP)and cardiac troponin I(c Tn I).Multivariate logistic regression was used to analyze the incidence of cardiovascular adverse events in patients with heart failure.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of heart rate variability in patient outcomes.The correlation between heart rate variability and the incidence of cardiovascular adverse events was analyzed by Kendall's tau-b analysis.Results There were significant differences in SDNN,SDANN,RMSSD,PNN50,cardiac function grade,LVEF and BNP level between the two groups(P<0.05).Through logistic regression analysis,SDNN,SDANN,RMSSD and PNN50 were independent predictors for the incidence of cardiovascular adverse events(P<0.05).The areas under curve for SDNN,SDANN,RMSSD,and PNN50 predicting of the incidence of cardiovascular adverse events were 0.732,0.732,0.758,and 0.819 respectively,and the sensitivity was 77.27%,81.81%,75.00%and 65.91%,respectively.The specificity was 61.11%,61.11%,80.56%,83.33%(P<0.05),respectively.Through Kendall's tau-b analysis,the index of heart rate variability was negatively correlated with the incidence of adverse cardiovascular events in patients with prognosis(P<0.05).Conclusions Heart rate variability has predictive value for the incidence of adverse cardiovascular events in patients with heart failure.The lower the heart rate variability,the higher incidence of cardiovascular adverse events.[S Chin J Cardiol 2024;25(3):135-141]

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.

Excess cardiovascular mortality in men with non-alcoholic fatty liver disease:A cause for concern!

Non-alcoholic fatty liver disease(NAFLD)has emerged as the commonest cause of chronic liver disease worldwide in recent years.With time,our understanding of NAFLD has evolved from an isolated liver condition to a systemic disease with significant manifestations beyond the liver.Amongst them,cardiovascular diseases(CVDs)are the most important and clinically relevant.Recent research supports a strong independent link between NALFD and CVD beyond the shared risk factors and pathophysiology.Female sex hormones are well known to not only protect against CVD in pre-menopausal females,but also contribute to improved adipose tissue function and preventing its systemic deposition.Recent research highlights the increased risk of major adverse cardiovascular-cerebral events(MACCE)amongst male with NAFLD compared to females.Further,racial variation was observed in MACCE outcomes in NAFLD,with excess mortality in the Native Americans and Asian Pacific Islanders compared to the other races.

Cardiovascular Risk of Opioids: A Real-World Study Based on FAERS

Objective:This research utilizes the FAERS for data mining to identify heart-related side effects caused by opioids,ensuring the safe use of these medications.Methods:Data from 79 quarters(Q12004 to Q32023)involving adverse event(AE)reports for opioids like morphine and oxycodone was reviewed.We applied the MedDRA system to categorize events and used statistical tools,ROR and BCPNN,for signal detection.These findings were cross-checked with drug labels and SIDER 4.1 for accuracy.Identified risks were then categorized by severity using DME and IME classifications.Results:Analysis of adverse events(AEs)for the five examined drugs(35359,14367,144441,10592,and 28848)identified 33,6,12,37,and 34 cardiovascular AEs,and 16,5,7,25,and 21 instances of important medical events(IMEs)respectively.Each drug was linked to cases of cardiac and cardiopulmonary arrest.The cardiovascular AEs varied widely in occurrence and severity,with methadone notably presenting diverse and potent risks,including sudden cardiac death as a distinct medical event(DME).A comparison with SIDER 4.1 showed 11 opioid-related cardiovascular AEs in line with our findings.Standardized MedDRA Queries(SMQs)confirmed these results,indicating stronger signals for methadone and tramadol,while morphine,hydromorphone,and oxycodone exhibited fewer and weaker signals.Conclusion:The study revealed numerous heart-related adverse effects(AEs)not listed on drug labels and identified new AE patterns.Recognizing these differences in AE profiles and risks across different opioids is crucial for safer prescription practices to minimize cardiac complications.

Left atrial area index predicts adverse cardiovascular events in patients with unstable angina pectoris

Background The left atrial size has been considered as a useful marker of adverse cardiovascular outcomes. However, it is not well known whether left atrial area index （LAAI） has predictive value for prognosis in patients with unstable angina pectoris （UAP）. This study was aimed to assess the association between LAAI and outcomes in UAP patients. Methods We enrolled a total of 391 in-hospital patients diag- nosed as UAP. Clinical and echocardiographic data at baseline were collected. The patients were followed for the development of ad- verse cardiovascular （CV） events, including hospital readmission for angina pectoris, acute myocardial infarction （AMI）, congestive heart failure （CHF）, stroke and all-cause mortality. Results During a mean follow-up time of 26.3±8.6 months, 98 adverse CV events occurred （84 hospital readmission for angina pectoris, four AMI, four CHF, one stroke and five all-cause mortality）. In a multivariate Cox model, LAAI [OR： 1.140, 95% CI： 1.01±1.279, P = 0.026], diastolic blood pressure （OR： 0.976, 95% CI： 0.956-0.996, P = 0.020） and pulse pressure （OR 1.020, 95% CI： 1.007-1.034, P = 0.004） were independent predictors for adverse CV events in UAP patients. Conclusions LAAI is a predictor of adverse CV events independent of clinical and other echocardiographic parameters in UAP patients.

Myeloperoxidase and High-Sensitivity C-Reactive Protein for Predicting Major Adverse Cardiovascular Events in Patients with Coronary Heart Disease

Background: Research has shown that high-sensitivity C-reactive protein (hs-CRP) is a major inflammatory marker for prediction of acute coronary syndrome (ACS). Myeloperoxidase (MPO) also plays an important role in atherosclerosis initiation and development. In present study, the major adverse cardiovascular events (MACEs) of patients with coronary heart disease (CHD) were investigated. Methods: MPO, hs-CRP and ACS-related risk factors from 201 ACS (78 AMI and 123 UAP) and 210 non-ACS (84 SAP and 126 non-CHD) patients confirmed by coronary angiography were detected, and the data were analyzed with receiver operating characteristic (ROC) curve and Spearman’s correlation coefficients. MACEs of 285 CHD patients were investigated during the 4-year period follow-up from March 2010 to May 2014. Results: The areas under ROC curve for diagnosing ACS were 0.888 (95% CI 0.843 - 0.933) for MPO, and 0.862 (95% CI 0.815-0.910) for hs-CRP, respectively. There were significantly correlations between MPO and hs-CRP in both ACS and non-ACS groups. Regarding to ACS patients, both MPO and hs-CRP were positively correlated with BMI, TC, TG, LDL-C and Hcy. Prospective study demonstrated that the incidences of MACEs associated significantly with elevated MPO baseline level (yes vs no, OR 7.383, 95% CI 4.095 - 13.309) and high hs-CRP baseline level (yes vs no, OR 4.186, 95% CI 2.469 - 7.097) in CHD patients. Conclusions: The present study provides the epidemiological evidence that elevated baseline MPO and hs-CRP levels are both valuable predictors of MACEs in CHD patients. MPO and hs-CRP would prompt the progression of atherosclerosis and development from SAP to ACS.

Knowledge,perceptions,and practice towards adverse events following immunization surveillance among vaccination workers in Zhejiang province,China

Objective:To access the level of knowledge,perceptions,and practice towards adverse events following immunization(AEFI)surveillance among vaccination workers in Zhejiang province,China.Methods:This was a cross-sectional survey involving 768 vaccination workers.Data were collected using self-administered questionnaires and analyzed by using SAS 9.3 software.Knowledge,perceptions,and practice on AEFI surveillance were summarized using frequency tables.The mean±SD value was used as the cut-off for defining good(values≥mean)and poor(values<mean)knowledge,perceptions or practice.Binary logistic regression analysis was used to determine sociodemographic variables associated with knowledge,perceptions,and practice towards AEFI.Results:The proportions of good knowledge,perceptions and practice on AEFI surveillance were 78.13%,57.81%and 66.15%,respectively.Having a higher education background,longer years of experience,previous training on AEFI and≥30 years of age were factors associated with good knowledge,perceptions and practice on AEFI surveillance among vaccination workers.Conclusions:Over half of the respondents had good knowledge,perceptions and practice on AEFI surveillance work.Interventions on improving the vaccination workers’knowledge,perceptions and practice on AEFI surveillance should be considered in order to develop a more effective surveillance system.

Correlation between immune-related adverse events and long-term outcomes in pembrolizumab-treated patients with unresectable hepatocellular carcinoma:A retrospective study

BACKGROUND Although immune checkpoint inhibitor(ICI)therapy has improved the prognosis of unresectable hepatocellular carcinoma(HCC),it has also resulted in unique immune-related adverse events(irAEs).The relationship between irAE and treatment outcomes in ICI-treated unresectable HCC patients remains unknown.AIM To elucidate the correlation between immune-related toxic effects and prognosis in patients with unresectable HCC treated with pembrolizumab.METHODS From March 2019 to February 2021,a total of 190 unresectable HCC(Barcelona Clinic Liver Cancer C)patients receiving pembrolizumab treatment were retrospectively reviewed.Overall survival(OS)was the primary endpoint,while objective response rate(ORR),disease control rate(DCR),and time to progression(TTP)were secondary evaluation indexes.We assessed demographics,irAEs,and outcomes by retrospective review.RESULTS One hundred and forty-three males and 47 females were included in the study.The ORR and DCR were 12.1%(23/190)and 52.1%(99/190),respectively.The median OS was 376 d[95%confidence interval(CI):340-411 d]and the median TTP was 98 d(95%CI:75-124 d).The overall incidence of treatment-related adverse events was 72.6%(138/190)and 10.0%of them were severe irAEs(grade≥3).Child-Pugh B class,portal vein tumor thrombus,extrahepatic metastasis,and hypothyroidism were the independent risk factors for survival.Patients with hypothyroidism showed a longer OS[517 d(95%CI:423-562)vs 431 d(95%CI:412-485),P=0.011]and TTP[125 d(95%CI:89-154)vs 87 d(95%CI:61-98),P=0.004]than those without irAEs.CONCLUSION Pembrolizumab-treated patients with unresectable HCC who experienced hypothyroidism have promising ORR and durable response.Hypothyroidism,an irAE,may be used as a clinical evaluation parameter of response to ICIs in unresectable HCC.

Immune-related adverse events induced by programmed death protein-1 inhibitors from the perspective of lymphoma immunotherapy

Lymphoma,which is highly malignant,stems from lymph nodes and lymphoid tissue.Lymphoma cells express programmed death-ligand 1/2(PD-L1/PD-L2),which binds with programmed cell death 1 protein(PD-1)to establish inhibitory signaling that impedes the normal function of T cells and allows tumor cells to escape immune system surveillance.Recently,immune checkpoint inhibitor immunotherapies such as PD-1 inhibitors(nivolumab and pembrolizumab)have been introduced into the lymphoma treatment algorithm and have shown remarkable clinical efficacy and greatly improve prognosis in lymphoma patients.Accordingly,the number of lymphoma patients who are seeking treatment with PD-1 inhibitors is growing annually,which results in an increasing number of patients developing immune-related adverse events(irAEs).The occurrence of irAEs inevitably affects the benefits provided by immunotherapy,particularly when PD-1 inhibitors are applied.However,the mechanisms and characteristics of irAEs induced by PD-1 inhibitors in lymphoma need further investigation.This review article summarizes the latest research advances in irAEs during treatment of lymphoma with PD-1 inhibitors.A comprehensive understanding of irAEs incurred in immunotherapy can help to achieve better efficacy with PD-1 inhibitors in lymphoma.

Maternal Hospital Mortality in Cotonou: Incidence, Care-Associated Adverse Events and Causes

Introduction: Despite the many efforts made to combat preventable maternal deaths, these still remain high in Benin. It was therefore important to revisit the causes but especially the adverse events associated with care (EIS) in maternity. Objective: Determine the incidence, adverse events associated with care and causes of intra hospital maternal mortality in cotonou. Methods: This was a cross-sectional maternal mortality review study with retrospective data collection. It covered all cases of maternal death recorded between 2017 and 2021 in two (2) reference university maternities in Cotonou. Adverse events associated with care and the patient were analyzed using the maternal death audit grid validated for Benin. SPSS.26 software was used for data analysis. Results: The in-hospital maternal mortality ratio in Cotonou was 2028 maternal deaths per 100,000 live births in 2021. Only 7.2% (n = 36) of deaths were audited. The deceased mothers were 29.8 ± 7.4 years old, with no fixed monthly income in 82.7% (n = 420). Serious adverse events associated with care were: delay in decision to refer in 37% (n = 188), non-medical referral in 85.8% (n = 436) of cases, inadequate pre-referral treatment in 25.7% of cases. In receiving maternities, delay in diagnosis and inappropriate treatment at the receiving maternity were noted respectively in 22.9% and 28.6% of cases of maternal death. The direct causes of maternal death were dominated by serious obstetric hemorrhage in 43.9% (n = 223). As for the indirect causes, they were dominated by anemia excluding obstetric hemorrhages in 21.5% (n = 109). Conclusion: The in-hospital maternal mortality ratio was very high in Cotonou. The main cause was severe obstetric hemorrhage. There were several serious healthcare-associated adverse events whose correct management would significantly reduce the incidence of maternal deaths.

Effects of adjuvant Chinese patent medicine therapy on major adverse cardiovascular events in patients with coronary heart disease angina pectoris:a population-based retrospective cohort study

Objective: This study aimed to explore the effects of Chinese patent medicine(CPM) in reducing the incidence of major adverse cardiovascular events(MACE) in patients with coronary heart disease(CHD) angina pectoris and improving clinical effectiveness and provide evidence for its use as clinical adjuvant therapy.Methods: Twenty-eight thousand five hundred and seventeen patients hospitalized with CHD angina pectoris from 6 hospitals were divided into CPM group(n = 11,374) and non-CPM group(n = 17,143) to evaluate the incidence of MACE, including myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting.Results: The incidence of MACE in the CPM group was lower than that in the non-CPM group. CPM therapy was an independent protective factor that reduced the overall risk of MACE [adjusted hazard ratio = 0.40, 95% confidence interval(0.33;0.49)]. Patients in the CPM group who received one, two, or three types of CPM could benefit from adjuvant treatment with CPM, and taking more types of CPM was associated with a lower risk of MACE. In addition, the male population was better than the female population at taking CPM, and middle-aged people aged 55 to 64 were more suited to take CPM based on Western medicine.Conclusions: The use of CPM as adjuvant therapy can decrease the occurrence of MACE in patients with CHD angina pectoris,especially in men and middle-aged people, and the drug treatment plan should be optimized accordingly. However, this conclusion needs further verification by prospective cohort studies in the future.

Control of modifiable risk factors and major adverse cardiovascular events in people with peripheral artery disease and diabetes

BACKGROUND People with diabetes and peripheral artery disease(PAD)have a high risk of major adverse cardiovascular events(MACE).Prior research suggests that medical therapies aimed to control modifiable risk factors are poorly implemented in patients with PAD.AIM To examine the association between the control of modifiable risk factors,estimated by the novel PAD-medical score,and the incidence of MACE in people with PAD and diabetes.METHODS Participants were recruited from out-patient clinics if they had a diagnosis of both PAD and diabetes.Control of reversible risk factors was assessed by a new composite measure,the PAD-medical score.This score takes into account the control of low-density lipoprotein cholesterol,blood pressure,blood glucose,smoking and prescription of an anti-platelet.Participants were followed to record incidence of myocardial infarction,stroke and cardiovascular death(MACE).The association of PAD-medical score with MACE was assessed using Cox proportional hazard analyses adjusting for age,sex and prior history of ischemic heart disease and stroke.RESULTS Between 2002 and 2020,a total of 424 participants with carotid artery disease(n=63),aortic or peripheral aneurysm(n=121)or lower limb ischemia(n=240)were prospectively recruited,and followed for a median duration(inter-quartile range)of 2.0(0.2–4.4)years.Only 33(7.8%)participants had the optimal PAD-medical score of five,with 318(75%)scoring at least three out of five.There were 89(21.0%)participants that had at least one MACE during the follow-up period.A one-unit higher PAD-medical score was associated with lower risk of MACE(HR=0.79,95%CI:0.63-0.98)after adjusting for other risk factors.CONCLUSION The PAD-medical score provides a simple way to assess the control of modifiable risk factors targeted by medical management aimed to reduce the incidence of MACE.