Social isolation, loneliness and subsequent risk of major adverse cardiovascular events among individuals with type 2 diabetes mellitus

Background Individuals with type 2 diabetes mellitus(T2DM)are more vulnerable to social disconnection compared with the general population;however,there are few relevant studies investigating this issue.Aims To investigate whether social isolation or loneliness may be associated with subsequent risk of developing major adverse cardiovascular events,whether these associations vary according to fatal and non-fatal outcomes and how behavioural,psychological and physiological factors mediate these associations.Methods This longitudinal analysis included data from 19360 individuals with T2DM at baseline(2006-2010)from the UK Biobank.Social isolation and loneliness were measured using self-report questionnaires.The study outcomes included the first events of myocardial infarction(MI)or stroke(n=2273)and all-cause(n=2820)or cardiovascular disease-related mortality through linked hospital data ordeath registries.Results Over a median follow-up of 12.4 years(interquartile range(IQR):11.6-13.3 years),participants who were more socially isolated(most social isolation vs least social isolation)experienced increased risks for all-cause(hazard ratio(HR):1.33,95%confidence interval(Cl):1.19 to 1.47)and cardiovascular disease(HR:1.36,95%Cl:1.17 to 1.59)mortality but not first Ml or stroke.Loneliness(yes vs no)was associated with a greater risk for a composite of incident MI or stroke(HR:1.37,95%Cl:1.19 to 1.57)but not mortality.Social isolation was associated with fatal Ml and stroke,whereas loneliness was associated with non-fatal Ml and stroke.The significant associations of social isolation and loneliness with outcomes were mainly mediated by behavioural factors(mediating proportion:17.8%-28.2%and 17.6%-17.8%,respectively).Conclusions Among individuals with T2DM,social isolation and loneliness are associated with a greater risk of developing major adverse cardiovascular events,with differences in both risks stratified according to fatal and non-fatal events and underlying mediating factors.

Association of accelerometer-measured sleep duration and different intensities of physical activity with incident type 2 diabetes in a population-based cohort study

Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort study.Methods:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK Biobank.Sleep duration(short:<6 h/day;normal:6-8 h/day;long:>8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and 2015.PA was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death registries.Results:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were documented.Compared with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes risk.This increased risk among short sleepers seems to be protected against by PA.Compared with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did not.Conclusion:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.

Wearable multilead ECG sensing systems using on-skin stretchable and breathable dry adhesives

Electrocardiogram(ECG)monitoring is used to diagnose cardiovascular diseases,for which wearable electronics have attracted much attention due to their lightweight,comfort,and long-term use.This study developed a wearablemultilead ECG sensing system with on-skin stretchable and conductive silver(Ag)-coated fiber/silicone(AgCF-S)dry adhesives.Tangential and normal adhesion to pigskin(0.43 and 0.20 N/cm2,respectively)was optimized by the active control of fiber density and mixing ratio,resulting in close contact in the electrode–skin interface.The breathableAgCF-S dry electrodewas nonallergenic after continuous fit for 24 h and can be reused/cleaned(>100 times)without loss of adhesion.The AgCF encapsulated inside silicone elastomers was overlapped to construct a dynamic network under repeated stretching(10%strain)and bending(90°)deformations,enabling small intrinsic impedance(0.3,0.1 Hz)and contact impedance variation(0.7 k)in high-frequency vibration(70 Hz).All hard/soft modules of the multilead ECG system were integrated into lightweight clothing and equipped with wireless transmission for signal visualization.By synchronous acquisition of I–III,aVR,aVL,aVF,and V4 lead data,the multilead ECG sensing system was suitable for various scenarios,such as exercise,rest,and sleep,with extremely high signal-to-noise ratios.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma:A network meta-analysis

BACKGROUND With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concentrations.However,there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study.The outcomes of interest comprised overall survival(OS),progression-free survival(PFS),tumor response and adverse events.Hazard ratios(HR)and odds ratios(OR)with a 95% confidence interval(CI)were calculated and agents were ranked based on their ranking probability.RESULTS HAIC outperformed Sorafenib(HR=0.55,95%CI:0.42-0.72;HR=0.51,95%CI:0.33-0.78;OR=2.86,95%CI:1.37-5.98;OR=5.45,95%CI:3.57-8.30;OR=7.15,95%CI:4.06-12.58;OR=2.89,95%CI:1.99-4.19;OR=0.48,95%CI:0.25-0.92,respectively)and transarterial chemoembolization(TACE)(HR=0.50,95%CI:0.33-0.75;HR=0.62,95%CI:0.39-0.98;OR=3.08,95%CI:1.36-6.98;OR=2.07,95%CI:1.54-2.80;OR=3.16,95%CI:1.71-5.85;OR=2.67,95%CI:1.59-4.50;OR=0.16,95%CI:0.05-0.54,respectively)in terms of efficacy and safety.HAIC+lenvatinib+ablation,HAIC+ablation,HAIC+anti-programmed cell death 1(PD-1),and HAIC+radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone.HAIC+TACE+S-1,HAIC+lenvatinib,HAIC+PD-1,HAIC+TACE,and HAIC+sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC.HAIC+PD-1,HAIC+TACE+S-1 and HAIC+TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.CONCLUSION HAIC proved more effective and safer than sorafenib and TACE.Furthermore,combined with other interventions,HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

Association of age at diagnosis of diabetes with subsequent risk of age-related ocular diseases and vision acuity

BACKGROUND The importance of age on the development of ocular conditions has been reported by numerous studies.Diabetes may have different associations with different stages of ocular conditions,and the duration of diabetes may affect the development of diabetic eye disease.While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality,whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored.It is unclear which types of diabetes are more predictive of ocular conditions.AIM To examine associations between the age of diabetes diagnosis and the incidence of cataract,glaucoma,age-related macular degeneration(AMD),and vision acuity.METHODS Our analysis was using the UK Biobank.The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis,and 6689 diabetic participants and 13378 controls for vision analysis.Ocular diseases were identified using inpatient records until January 2021.Vision acuity was assessed using a chart.RESULTS During a median follow-up of 11.0 years,3874,665,and 616 new cases of cataract,glaucoma,and AMD,respectively,were identified.A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age.Individuals with type 2 diabetes(T2D)diagnosed at<45 years[HR(95%CI):2.71(1.49-4.93)],45-49 years[2.57(1.17-5.65)],50-54 years[1.85(1.13-3.04)],or 50-59 years of age[1.53(1.00-2.34)]had a higher risk of AMD independent of glycated haemoglobin.T2D diagnosed<45 years[HR(95%CI):2.18(1.71-2.79)],45-49 years[1.54(1.19-2.01)],50-54 years[1.60(1.31-1.96)],or 55-59 years of age[1.21(1.02-1.43)]was associated with an increased cataract risk.T2D diagnosed<45 years of age only was associated with an increased risk of glaucoma[HR(95%CI):1.76(1.00-3.12)].HRs(95%CIs)for AMD,cataract,and glaucoma associated with type 1 diabetes(T1D)were 4.12(1.99-8.53),2.95(2.17-4.02),and 2.40(1.09-5.31),respectively.In multivariable-adjusted analysis,individuals with T2D diagnosed<45 years of age[β95%CI:0.025(0.009,0.040)]had a larger increase in LogMAR.Theβ(95%CI)for LogMAR associated with T1D was 0.044(0.014,0.073).CONCLUSION The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.

DNA Methylation Variation Is Identified in Monozygotic Twins Discordant for Congenital Heart Diseases

Aims:Multiple genes and environmental factors are known to be involved in congenital heart disease(CHD),but epigenetic variation has received little attention.Monozygotic(MZ)twins with CHD provide a unique model for exploring this phenomenon.In order to investigate the potential role of Deoxyribonucleic Acid(DNA)methyla-tion in CHD pathogenesis,the present study examined DNA methylation variation in MZ twins discordant for CHD,especially ventricular septal defect(VSD).Methods and Results:Using genome-wide DNA methylation profiles,we identified 4004 differentially methylated regions(DMRs)in 18 MZ twin pairs discordant for CHD,and 2826 genes were identified.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed a list of CHD-associated pathways.To further investigate the role of DNA methylation in VSD,data from 7 pairs of MZ twins with VSD were analyzed.We identified 1614 DMRs corresponding to 1443 genes associated with arrhythmogenic right ventricular cardiomyopathy,cyclic guanosine monopho-sphate-protein kinase G(cGMP-PKG)signaling pathway by KEGG analysis,and cell-cell adhesion,calcium ion transmembrane transport by GO analysis.A proportion of DMR-associated genes were involved in calcium signaling pathways.The methylation changes of calcium signaling genes might be related to VSD pathogenesis.Conclusion:CHD is associated with differential DNA methylation in MZ twins.CHD may be etiologically linked to DNA methylation,and methylation of calcium signaling genes may be involved in the development of VSD.

Circadian rhythm dysfunction and psychopathology in the offspring of parents with bipolar disorder:a highrisk study in the Chinese population

Background Understanding the evolution of circadian rhythm dysfunction and psychopathology in the high-risk population has important implications for the prevention of bipolar disorder.Nevertheless,some of the previous studies on the emergence of psychopathologies and circadian dysfunction among high-risk populations were inconsistent and limited.Aims To examine the prevalence rates of sleep and circadian dysfunctions,mental disorders and their symptoms in the offspring of parents with(O-BD)and without bipolar disorder(O-control).Methods The study included 191 O-BD and 202 O-control subjects aged 6-21 years from the Greater Bay Area,China.The diagnoses and symptoms of sleep/circadian rhythm and mental disorders were assessed by the Diagnostic Interview for Sleep Patterns and Disorders,and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version,respectively.Generalised estimating equations and shared frailty proportional hazards models of survival analysis were applied to compare the outcomes in the offspring.Results Adjusting for age,sex and region of recruitment,there was a significantly higher risk of delayed sleep phase symptoms(9.55%vs 2.58%,adjusted OR:4.04)in O-BD than in O-control.O-BD had a nearly fivefold higher risk of mood disorders(11.70%vs 3.47%,adjusted OR:4.68)and social anxiety(6.28%vs 1.49%,adjusted OR:4.70),a fourfold higher risk of depressive disorders(11.17%vs 3.47%,adjusted OR:3.99)and a threefold higher risk of mood symptoms(20.74%vs 10.40%,adjusted OR:2.59)than O-control.Subgroup analysis revealed that O-BD children(aged under 12 years)had a nearly 2-fold higher risk of any mental and behavioural symptoms than O-control,while there was a nearly 4-fold higher risk of delayed sleep phase symptoms,a 7.5-fold higher risk of social anxiety and a 3-fold higher risk of mood symptoms in O-BD adolescents(aged 12 years and over).Conclusions There was an increase in delayed sleep phase symptoms in O-BD adolescents compared with their control counterparts,confirming the central role of circadian rhythm dysfunction in bipolar disorder.The findings of the specific age-related and stage-related developmental patterns of psychopathologies and circadian dysfunction in children and adolescent offspring of parents with bipolar disorder paved the way to develop specific and early clinical intervention and prevention strategies.

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.

Genetic and epigenetic predispositions underlying cardiovascular outcomes among patients treated with clopidogrel and aspirin

Coronary artery disease(CAD) is a major cause of death and disability worldwide,and consumes a considerable amount of medical resources every year.Clopidogrel is a first-line antiplate.let therapy for CHD,butit is associated with substantial variability in PK and pharmacodynamics re.sponse.To date,gene variants explain only a smallproportion of the variability.The study aimed to identify new genetic loci-modifying antiplatelet response to clopidogrel in Chinese patients with CAD by a systematic analysis combining antiplatelet effects and PK,and further to investigate the PON1 gene promoter DNA methylation and genetic variations possibly influencing clinical outcomes in pa.tients undergoing PCI.We identified novel variants in two transporter genes(SLC14 A2 rs12456693,ATP-binding cassette [ABC]A1 rs2487032) and in N6 AMT1(rs2254638) associated with P2Y12 reaction unit(PRU) and plasma active metabolite(H4) concentration.These new variants dramatically im.proved the predictability of PRU variability to 37.7%.The associations between these loci and PK pa.rameters of clopidogrel and H4 were observed in additional patients,and its function on the activation of clopidogrel was validated in liver S9 fractions(P<0.05).Rs2254638 was further identified to exert a marginal risk effect formajor adverse cardiac events in an independent cohort.Multivariate logistic regression analysis indicated that PON1 methylation level at CpG site-161(OR=0.95;95% CI=0.92–0.98;P<0.01) and the use of angiotensin converting enzyme inhibitors(OR=0.48;95% CI=0.26–0.89;P<0.01) were associated with decreased risk of bleeding events.In conclusion,new genetic variants were systematically identified as risk factors for the reduced efficacy of clopidogrel treatment.The ab.normal expression of DNA methylation-regulating key genes in the pharmacokinetic and pharmacody.namics pathways of clopidogrel and aspirin may modify clinical outcomes in dual antiplatelet-treated patients undergoing PCI.

Food Intake Habit and Cardiovascular Risk

To determine the relationshipof dietary factors to cardiovascular disease, surveys were carried out in 1985 (pilot study) and 1989 (core study) as a part of the International Cooperative Cardiovascular Diseases and Alimentary Comparison (CARDIAC) study. Food pattern was observed and blood pressure was measured with an automatic electronic sphygromanometer. The diet in Guangzhou seems more refined, fresher and offers more variety than that in the other areas in China. Both systolic and diastolic blood pressure have risen in the period of socioeco-nomic development. Food intake habits are changing in Guangdong, China, with a trend toward an unhealthy diet which increases the risk of cardiovascular disease.

Prevalence and incidence of heart failure among community in China during a three-year follow-up

BACKGROUND Epidemiological surveys on heart failure(HF)in Chinese community are relatively lacking.This study aimed to estimate the prevalence and incidence of HF among community residents in southern China.METHODS Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged≥35years in Guangzhou,China.The same survey process was carried out for individuals aged≥65 years after a three-year follow-up.RESULTS The overall prevalence of HF in community residents aged≥35 years was 1.06%.Male had significantly higher risk of HF prevalence[odds ratio(OR)=1.50,P=0.027].The gender-adjusted risk of HF was 1.48 times higher per 10 years aging.HF prevalence was statistically associated with atrial fibrillation,valvular heart disease,hypertension and chronic obstructive pulmonary disease after adjusting for age and gender(OR=8.30,5.17,1.11,2.28,respectively;all P<0.05).HF incidence in individuals aged≥65 years were 847 per 100,000 person-years.Baseline atrial fibrillation,valvular heart disease,and diabetes mellitus were risk factors for HF incidence for individuals aged≥65 years adjusting for age and gender(OR=5.05,3.99,2.11,respectively;all P<0.05).Besides,residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF(OR=14.41,8.54,respectively;all P<0.05).CONCLUSIONS Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China.Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.

Intermediate and Long-Term Follow-Up of Transcatheter Closure of Congenital Coronary Cameral Fistulas in Infants and Children:Experience from a Single Center

Background:Limited data are available regarding intermediate and long-term outcomes of transcatheter closure(TCC)of coronary cameral fistulas(CCFs)in the pediatric patients.Methods:All pediatric patients diagnosed with CCFs who were scheduled to undergo TCC between 2005 and 2019 were retrospectively enrolled in the study.Results:A total of 66 patients(median age:3.93 years,median weight:15 kg)underwent attempted TCC of CCFs.Immediate successful device implantation was achieved in 62 patients,and immediate complete occlusion was achieved in 44 patients(44/62%,71.0%).The closure procedure was waived in 2 patients due to anatomical factors.A total of 6 periprocedural complications occurred in 5 patients,including acute myocardial infarction(n=3),procedure-related death(n=1),device embolization(n=1),and rupture of tricuspid chordae tendineae(n=1).The acute procedural success rate was 89.4%(59/66),while the acute complication rate was 9.1%(6/66).Follow-up data were collected for 58(93.5%)out of 62 patients at a median of 9.3 years(range:3.0–15.7 years).10 adverse events occurred in 9 patients,including 5 follow-up complications(1 aortic valve perforation,1 coronary thrombosis,1 progressive aneurysmal dilation after reintervention,and 2 cases of new-onset tricuspid valve prolapse with significant regurgitation),and 5 closure failure with large residual shunts.The intermediate and long-term adverse event rate was 17.2%(10/58).The anatomical features associated with both acute and follow-up adverse events were large CCFs(p=0.005),and giant coronary artery aneurysms(CAAs)(p=0.029).Conclusions:TCC of CCFs in infants and children appears to be effective and is associated with a relatively low complication rate.Large CCFs and giant CAAs represent a higher risk of both acute and intermediate and long-term adverse events after closure.

Cardiopulmonary prognosis of prophylactic endotracheal intubation in patients with upper gastrointestinal bleeding undergoing endoscopy

BACKGROUND:It is controversial whether prophylactic endotracheal intubation(PEI)protects the airway before endoscopy in critically ill patients with upper gastrointestinal bleeding(UGIB).The study aimed to explore the predictive value of PEI for cardiopulmonary outcomes and identify high-risk patients with UGIB undergoing endoscopy.METHODS:Patients undergoing endoscopy for UGIB were retrospectively enrolled in the eICU Collaborative Research Database(eICU-CRD).The composite cardiopulmonary outcomes included aspiration,pneumonia,pulmonary edema,shock or hypotension,cardiac arrest,myocardial infarction,and arrhythmia.The incidence of cardiopulmonary outcomes within 48 h after endoscopy was compared between the PEI and non-PEI groups.Logistic regression analyses and propensity score matching analyses were performed to estimate effects of PEI on cardiopulmonary outcomes.Moreover,restricted cubic spline plots were used to assess for any threshold effects in the association between baseline variables and risk of cardiopulmonary outcomes(yes/no)in the PEI group.RESULTS:A total of 946 patients were divided into the PEI group(108/946,11.4%)and the non-PEI group(838/946,88.6%).After propensity score matching,the PEI group(n=50)had a higher incidence of cardiopulmonary outcomes(58.0%vs.30.3%,P=0.001).PEI was a risk factor for cardiopulmonary outcomes after adjusting for confounders(odds ratio[OR]3.176,95%confidence interval[95%CI]1.567-6.438,P=0.001).The subgroup analysis indicated the similar results.A shock index>0.77 was a predictor for cardiopulmonary outcomes in patients undergoing PEI(P=0.015).The probability of cardiopulmonary outcomes in the PEI group depended on the Charlson Comorbidity Index(OR 1.465,95%CI 1.079-1.989,P=0.014)and shock index>0.77(compared with shock index≤0.77[OR 2.981,95%CI 1.186-7.492,P=0.020,AUC=0.764]).CONCLUSION:PEI may be associated with cardiopulmonary outcomes in elderly and critically ill patients with UGIB undergoing endoscopy.Furthermore,a shock index greater than 0.77 could be used as a predictor of a worse prognosis in patients undergoing PEI.

Maternal Vascular Dysfunction in Congenital Heart Defects

Background:Research on fetal congenital heart defect(CHD)mostly focuses on etiology and mechanisms.However,studies on maternal complications or pathophysiology are limited.Our objective was to determine whether vascular dysfunction exists in pregnant women carrying a fetus with congenital heart defects.Methods:We conducted a case-control study.27 cases of pregnant women carrying a fetus with major CHD admitted to our hospital for delivery between April 2021 and August 2022 were selected.Every case was matched with about 2 pregnant complication-free controls without fetal abnormalities.The proangiogenic and anti-angiogenic factors and pregnancy outcomes were compared.Results:The proangiogenic factors include vascular endothelial growth factor(VEGF)and placental growth factor(PlGF).The anti-angiogenic factors involve soluble fms-like tyrosine kinase 1(sFlt-1)and soluble endoglin(sEng).No differences were found in maternal plasma concentrations of PlGF,VEGF,and sFlt-1 between case-control groups when analyzed at 36 weeks≤gestational age(GA)<39 weeks and 39 weeks≤GA≤41 weeks.The concentrations of sEng in maternal plasma in the fetal CHD group were significantly higher than those in the control group:0.60(0.77)vs.0.32(0.26)ng/ml at 36 weeks≤GA<39 weeks,p=0.001 and 0.75(0.55)vs.0.28(0.27)ng/ml at 39 weeks≤GA≤41 weeks,p<0.001.Conclusion:Vascular dysfunction exists in pregnant women with fetal congenital heart defects,manifesting significantly elevated sEng concentration at delivery.

Laboratory scoring system to predict hepatic indocyanine green clearance ability during fluorescence imaging-guided laparoscopic hepatectomy

BACKGROUND Indocyanine green(ICG)fluorescence played an important role in tumor localization and margin delineation in hepatobiliary surgery.However,the preoperative regimen of ICG administration was still controversial.Factors associated with tumor fluorescence staining effect were unclear.AIM To investigate the preoperative laboratory indexes corelated with ICG fluorescence staining effect and establish a novel laboratory scoring system to screen specifical patients who need ICG dose adjustment.METHODS To investigate the predictive indicators of ICG fluorescence characteristics in patients undergoing laparoscopic hepatectomy from January 2018 to January 2021 were included.Blood laboratory tests were completed within 1 wk before surgery.All patients received 5 mg ICG injection 24 h before surgery for preliminary tumor imaging.ImageJ software was used to measure the fluorescence intensity values of regions of interest.Correlation analysis was used to identify risk factors.A laboratory risk model was established to identify individuals at high risk for high liver background fluorescence.RESULTS There were 110 patients who were enrolled in this study from January 2019 to January 2021.The mean values of fluorescence intensity of liver background(FI-LB),fluorescence intensity of gallbladder,and fluorescence intensity of target area were 18.87±17.06,54.84±33.29,and 68.56±36.11,respectively.The receiver operating characteristic(ROC)curve showed that FI-LB was a good indicator for liver clearance ability[area under the ROC curve(AUC)=0.984].Correlation analysis found pre-operative aspartate aminotransferase,alanine aminotransferase,gammaglutamyl transpeptidase,adenosine deaminase,and lactate dehydrogenase were positively associated with FI-LB and red blood cell,cholinesterase,and were negatively associated with FI-LB.Total laboratory risk score(TLRS)was calculated according to ROC curve(AUC=0.848,sensitivity=0.773,specificity=0.885).When TLRS was greater than 6.5,the liver clearance ability of ICG was considered as poor.CONCLUSION Preoperative laboratory blood indicators can predict hepatic ICG clearance ability.Surgeons can adjust the dose and timing of ICG preoperatively to achieve better liver fluorescent staining.

Resolving vertebrate brain evolution through salamander brain development and regeneration

The emergence of the brain was a radical event in evolution.The global architecture of the brain is established during early embryonic development and is highly correlated with its function, with considerable morphological similarities across diverse vertebrates(Figure 1A). With evolution, however,neuronal diversity and spatial distribution of neuronal subtypes and circuits generally become more complex in the brain.

Cardiovascular toxicity with CTLA-4 inhibitors in cancer patients:A meta-analysis

Background:With the emergence of cytotoxic T lymphocyte-associated protein-4(CTLA-4)inhibitors,the outcomes of patients with malignant tumors have improved significantly.However,the incidence of cardiovascular adverse events has also increased,which can affect tumor treatment.In this study,we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor therapy.Methods:Randomized clinical trials published in English from January 1,2013,to November 30,2022,were searched using the Cochrane Library and PubMed databases.All included trials examined all grade and grades 3–5 cardiac and vascular adverse events.These involved comparisons of CTLA-4 inhibitors to placebo,CTLA-4 inhibitors plus chemotherapy to chemotherapy alone,CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone,and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target agent.The odds ratio(OR)and corresponding 95%confidence intervals(CIs)were calculated using the Mantel-Haenszel method.Results:Overall,20 trials were included.CTLA-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity(OR=1.33,95%CI:1.00–1.75,p=0.05).The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors(OR=1.73,95%CI:1.13–2.65,p=0.01),as well as the incidence rate of grades 3–5 cardiovascular adverse events(OR=2.00,95%CI:1.08–3.70,p=0.03).Compared with the non-CTLA-4 inhibitor group,CTLA-4 inhibitors plus chemotherapy,PD-1/PD-L1 inhibitors,or target agent did not significantly affect the incidence of cardiac and vascular toxicity.The incidence of grades 3–5 cardiac failure,hypertension,pericardial effusion,myocarditis,and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor,but the data were not statistically significant.Conclusion:Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA-4 inhibitors.In addition,the risk of serious cardiovascular toxic events was independent of the type of adverse event.From these results,physicians should assess the benefits and risks of CTLA-4 inhibitors when treating malignancies.

Expert Consensus on Nutritional Support for Children with Congenital Heart Disease(2023 Edition)

The second edition of the expert consensus on pediatric nutrition was formed based on a global update of pedia-tric nutrition guidelines or consensus worldwide,the management of congenital heart disease,and the results of multi-center clinical nutrition research for congenital heart disease following thefirst Chinese consensus edition of 2016.The consensus was also shaped by the results of three discussion sessions and two questionnaires con-ducted by the 13-member collaboration group.This process was informed by both clinical guidelines and expert consensus.The quality of literature,both in English and Chinese,and the level of recommendations were evaluated using the Grading of Recommendations Assessment,Development,and Evaluations(GRADE)system.

Transcatheter closure of ventricular septal defect in patients with aortic valve prolapse and mild aortic regurgitation:feasibility and preliminary outcome

Objective:To evaluate the feasibility,safety and efficacy of transcathcter closure of ventricular septal defect(VSD)in patients with aortic valve prolapse(AVP)and mild aortic regurgitation(AR).Methods:Between January 2008 and July 2014,transcatheter closure of VSD was attempted in 65 patients.Results:The total intermediate closure successful rate in all subjects was 96.9%.During the perioperative period,no death,major bleeding,pericardial tamponade,occluder dislodgement,residual shunt or hemolysis occurred.Two procedures had been forced to suspend due to significant aggregation of device related aortic regurgitation,three cases of transient complete left bundle branch block occurred but did not sustain.At 1-year followup,no patients had residual shunts and complications.Furthermore,grade of residual AR were relieved in 61.9%(39/63)cases and degree of AVP were ameliorated in 36.5%(23/63)patients;Conclusions:Transcatheter closure VSD in selected patients with AVP and mild AR is technically feasible and highly effective.Long term safety and efficacy needs to be assessed.