Analysis of families with fetal congenital abnormalities but negative prenatal diagnosis by whole exome sequencing / 中华妇产科杂志

Objective:To evaluate the value of whole exome sequencing (WES) in prenatal clinical application.Methods:A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed.Results:Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results.Conclusions:WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.

Research on relevant factors and the value on prenatal ultrasound diagnosis for coarctation of the aorta / 中华超声影像学杂志

To improve the accuracy of prenatal diagnosis for coarctation of the aorta ( CoA ) by comparatively analyzing the relevant factors and their application value . Methods Cases of disproportion of ventricles and great vessels were selected between January 2011 and July 2018 . Only liveborn fetuses with complete postnatal follow‐up were included in the study . One hundred and twelve cases were retrieved and analyzed . According to the postnatal ultrasound and CT results ,the patients were divided into gruop A and goup B . Different fetal echocardiography parameters and features were selected to evaluate the diagnostic value . Logistic regression analysis was used to select the best predictors of CoA and optimal cut‐offs for these parameters were identified by ROC analysis . Results One hundred and thirty eight fetuses were suspected to be CoA ,and 112 of them were born . T hey included 59 cases ( 52 .9% ) with CoA ( Group A ) and 53 cases ( 47 .3% ) without CoA ( Group B ) . T here were statistically significant differences between the two groups in gestational age ,Z‐score of diameter of left ventricle ,ascending aorta ( AAO ) and aortic arch isthmus ,main pulmonary artery ( M PA )/AAO diameters ratio ,and arterial duct/isthmus diameters ratio . T he parameters most predictive of postnatal CoA selected by logistic regression and the cut‐off values identified by ROC analysis were :gestational age at first diagnosis ≤34 .5 weeks ,Z‐score of diameter of left ventricle ＜ －1 .8 ,Z‐score of diameter of isthmus ＜ －2 .7 ,M PA/AAO diameters ratio＞1 .6 . AUC yielded by these parameters in combination was 0 .94 ( 95% CI :0 .89 －0 .99) . T he study group were divided into two subgroups by gestational age at first diagnosis .T he parameters and cut‐off values in subgroups were selected by the same analysis as above :Group Ⅰ ( ≤ 34 .5 weeks ) ,Z‐score of diameter of right ventricle ＞2 .1 ,M PA/AAO diameters ratio＞1 .6 ; Group Ⅱ( ＞34 .5 weeks) ,M PA/AAO diameters ratio ＞ 1 .7 ,arterial duct/isthmus diameters ratio ＞ 2 .3 . Meanw hile ,some ultrasound features ( including aortic arch hypoplasia ,retrograde blood flow of aortic isthmus ) should also be considered to improve diagnostic accuracy . Conclusions Combined with the use of different ultrasound parameters and features at different gestational weeks can improve the accuracy of the prenatal diagnosis of CoA in the right heart dominant fetus .

Relationship between overnight urinary sodium to potassium ratio and the risk of cardiovascular disease / 中华心血管病杂志

Objective@#To explore the relationship between overnight urinary sodium to potassium ratio and the risk of cardiovascular disease (CVD).@*Methods@#A subsample of 10 percent of the participants (35-59 years old) from the People's Republic of China-United States Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology (prospective survey) were used. Three consecutive overnight urine samples were collected in the autumn of 1983-1984 and the spring in 1985-1986, respectively. Urinary sodium and potassium were detected and calculated for 8 hours excretion. The occurrences of cardiovascular events were recorded in 2 years interval from 1987-1988 until December 31, 2005. Participants were divided into first ratio group, second ratio group, and third ratio group based on the tertiles of sodium to potassium ratio. Cox proportional hazard regression model was used to determine the relationship between sodium to potassium ratio and risk of CVD. In addition, participants were divided into 2 subgroups by the median of overnight urinary sodium and potassium, and then combined each other for 4 subgroups including low sodium-low potassium group, low sodium-high potassium group, high sodium-low potassium group, and high sodium-high potassium group, to explore the relationship between different sodium-potassium combinations and the risk of CVD.@*Results@#A total of 954 participants were included in the final analysis, of whom 459 (48.1%) were males. There were 318 cases in the first, second and third ratio group, respectively. There were 347 cases in low sodium-low potassium group and high sodium-high potassium group, and 130 cases in low sodium-high potassium group and high sodium-low potassium group. After a median follow-up of 18.6 (18.3, 19.3) years, cardiovascular events occurred in 81 participants, including 64 stroke and 20 coronary heart disease events. Multivariate analysis showed that comparing with the first ratio group, the hazard ratios (HR) in the second and the third ratio groups were 2.04 (95%CI 1.06-3.95, P=0.034) and 2.07 (95%CI 1.07-4.03, P=0.032), respectively. The CVD risk in low sodium-low potassium group was 24% higher than the low sodium-high potassium group (reference), but this result did not reach statistical significant level (P=0.685). The risks in high sodium-high potassium group (HR=3.32, 95%CI 1.26-8.76,P=0.015) and high sodium-low potassium (HR=3.04, 95%CI 1.05-8.83, P=0.041) group were both significantly increased.@*Conclusions@#Overnight urinary sodium to potassium ratio is positively correlated with the risk of cardiovascular events. High urinary sodium plays a more important role for the increased risk of cardiovascular events than low potassium.

Effect of minimized cardiopulmonary bypass circuit on perioperative mortality in neonates with congenital heart dis-ease / 中华胸心血管外科杂志

Objective To explore the effect of the surgical treatment in neonates with congenital heart disease(CHD) and the factors related to the perioperative mortality during cardiopulmonary bypass. Methods Totally,666 neonates undergo-ing CHD operation were reviewed in a single center from Jan 2006 to Dec 2014,of which,431 cases had complete cardiopul-monary bypass records. Analysis was performed to investigate the association between perioperative mortality and potential fac-tors,especially the cardiopulmonary bypass factors during different periods. In the multivariate Cox proportional hazard model, factors with statistical significance(P < 0. 1)in the univariate analysis were included in the model,such as,surgeon grouping, year of surgery,Aristotle score,preoperative weight,preoperative and intraoperative sodium bicarbonate volume and postopera-tive low cardiac output. Results The neonates enrolled ranged 8 - 22 days after birth,and 2. 7 - 3. 6 kg at weight. The mor-tality rate decreased from 23. 7％ in 2006 to 12. 4％ in 2014,showing a gradual decline(P = 0. 02). The mortalities of differ-ent CHDs were:pulmonary atresia(24. 4％),coarctation of the aorta( 16. 7％),transposition of the great arteries( 13. 1％), total anomalous pulmonary venous connection( 11. 0％),ventricular septal defect( 10. 6％),and so on. The volume of preop-erative and intraoperative 5％ sodium bicarbonate was 30(20 - 50)mL in death group,higher than that in survival group[23 ( 15 - 30)ml]. While the preoperative weight was 3. 1(2. 7 - 3. 5)kg,lower than that in survival group[3. 3(3. 0 - 3. 6) kg]. The total amount of Plasmalyte/ Ringer,erythrocytes,ultrafiltration volume and the cardiac assist ratio were higher in the death group than in the survival group. After controlling the confounding effect of surgeons,the multivariable Cox proportional hazard model showed that:the independent risk factors for perioperative mortality were pulmonary atresia[aHR = 3. 89( 1. 78 -8. 42)],5％ sodium bicarbonate volume ≥50 ml[aHR = 2. 62( 1. 14 - 6. 04)],erythrocytes volume > 200 ml[aHR = 2. 26 ( 1. 1 - 4. 06)]and postoperative low cardiac output[aHR = 6. 76(3. 30 - 13. 87)]. Conclusion During the study period, the preoperative mortality for neonates with CHD had a dramatical decrease,although the preoperative risk factors for the pa-tients increased. Pulmonary atresia repair surgery had the highest mortality in neonates. Factors associated with the periopera-tive mortality includedpreoperative acidosis and postoperative low cardiac output. There is a significant association between the improvement of perioperative mortality and the improvement of the technology of minimized cardiopulmonary bypass circuit dur-ing neonatal operation. It is suggested that the total erythrocytes volume maintains less than 200 ml.

A new perspective of survival data on clinical epidemiology: introduction of competitive risk model / 中华流行病学杂志

Competing risks occur frequently in the analysis of survival data that should be dealt with competing risk models.Competing risk is an event whose occurrence precludes the occurrence of the primary event of interest.Previous commonly used Kaplan-Meier method tends to overestimate the cumulative survival functions,while the traditional Cox proportional hazards model falsely evaluates the effects of covariates on the hazard related to the occurrence of the event.There are few domestic reports mentioning the concept,application and methodology of competing risk model as well as the implementation procedures or resolution of model conditions and parameters.The current work aims to explain the core concept and methodology of the competing risk model and to illustrate the process of analysis on cumulative incidence rate,using both the cause-specific hazard function model and the sub-distribution hazard function model.Software macro code in SAS 9.4 is also provided to assist clinical researchers to further understand the application of the model so to properly analyze the survival data.

A new perspective of survival data on clinical epidemiology: introduction of competitive risk model / 中华流行病学杂志

Competing risks occur frequently in the analysis of survival data that should be dealt with competing risk models.Competing risk is an event whose occurrence precludes the occurrence of the primary event of interest.Previous commonly used Kaplan-Meier method tends to overestimate the cumulative survival functions,while the traditional Cox proportional hazards model falsely evaluates the effects of covariates on the hazard related to the occurrence of the event.There are few domestic reports mentioning the concept,application and methodology of competing risk model as well as the implementation procedures or resolution of model conditions and parameters.The current work aims to explain the core concept and methodology of the competing risk model and to illustrate the process of analysis on cumulative incidence rate,using both the cause-specific hazard function model and the sub-distribution hazard function model.Software macro code in SAS 9.4 is also provided to assist clinical researchers to further understand the application of the model so to properly analyze the survival data.

Early-and intermediate-term results of surgical correction in 328 patients with different drainage type of total anoma-lous pulmonary venous connection / 中华胸心血管外科杂志

Objective This retrospective cohort study aims to evaluate and compare the prognosis of surgical repair for total anomalous pulmonary venous connection(TAPVC) with different drainage type.Methods From January 2006 to Decem-ber 2013, 328 consecutive patients were enrolled in this study .The distribution of the defects was 109 cases with cardiac, 161 with supracardiac, 32 with infracardiac, and 26 with mixed type of the drainage into the systemic circulation .The clinical re-cords of all the patients were reviewed.Studied variables were extracted from the clinical records.Followed-up was conducted at an interval of 1 month, 3 months, 6 months and then once a year post-operation.Prevalence of peri-operative conditions were compared among four different types.Studied endpoints was defined by postoperative total death or pulmonary venous obstruc-tion(PVO), which was evaluated with Kaplan-Meier curve and multivariable Cox proportional hazard model, adjusted by differ-ent surgical strategy, emergency operation, preoperative-PVO, neonates, weight, combing with other complex cardiac defects,NYHA cardiac function, severe pulmonary hypertension and severe tricuspid regurgitation.Results There were significant discrepancyof preoperative conditions among four types of TAPVC.Patients with infracardiac TAPVC presented the most criticalsymptoms and clinical indexes, which included having largest proportion of neonates, preoperative PVO, severe NYHA grading,pulmonary hypertension and tricuspid regurgitation, having lowest body weight at operation and youngest age.The cardiopulmonarybypass time, aortic crossclamp time and mechanical ventilation time were significantly longer in infracadiac and mixedTAPVC comparing to the other two types.For early mortality(death in hospital), infracadiac(9.4%) and mixed(11.5%)TAPVC demonstrated higher rates of death than cardiac(4.6%) and supracardiac(7.5%)TAPVC, although had no statisticalsignificance.For intermediate-term results, mortality in infracadiac(21.9%) and mixed(30.8%) TAPVC were significantlyhigher than cardiac ( 8.3%) and supracardiac (11.8%) TAPVC.Reoperation was more frequently required in mixed(19.2%), then infracadiac(15.6%)TAPVC.Mixed and infracadiac types are independent risk factors for TAPVC prognosis,after adjusting by the confounding factors.Conclusion Mixed and infracadiac types are independent risk factors for postoperativedeath and PVO among TAPVC patients.This study provided evidence for clinical assessment and management strategy fordifferent types of TAPVC.

Comparison between Two Surgical Techniques to Repair Total Anomalous Pulmonary Venous Connection Using propensity Scoreanalysis / 中山大学学报(医学科学版)

[Objective]To evaluate the effects of sutureless technique in comparison to conventional techniques for repair of total anomalous pulmonary venous connection(TAPVC)with the method of propensity score analysis.[Methods]From October 2007 to December 2013,179 consecutive patients were enrolled in this study. Patients were operated with sutureless technique(n = 81)or Conventional technique(n=98),and followed up at an interval of 1 month,3 months,6 months and then once a year post-operation. During analysis,three type of propensity-score matching methods,including nearest neighbor caliper matching,Mahalanobis metric matching with propensity score ,optimal full matching were used to create balanced groups of patients receiving each treatment. Surgeons’performance difference was assessed with random frailty proportional hazards models with gamma. Composite endpoints was defined by postoperative death or late death or postoperative pulmonary venous obstruction(PVO),which was evaluated with Kaplan-Meier curve and multivariable Cox proportional hazard model,adjusted by Preoperative-PVO,age,gender,weight and TAPVC type.[Results]Nearest neighbor caliper matching method was the best choice during propensity score analysis. After matching ,sutureless group included 73 patients and Conventional group73 patients. In sutureless group,cardiopulmonary bypass(CPB)time(Z=2.18, P=0.030),cross-clamp time(Z=3.63,P<0.001),rate of composite endpoints(HR 95%CI=0.20(0.06~0.61),P=0.005),late death(HR 95%CI=0.03(0.01~0.55),P=0.017)were significantly better than that in Conventional group. In subgroup analysis ,for patients with pre-PVO,decreased composite endpoints was seen in sutureless group.[Conclusion]Comparison using thepropensity score analysis demonstrated that sutureless strategy for primary repair of TAPVC may associate with decreased mortality rate of post-PVO and CPB time and cross-clamp time.

Application of SAS macro to evaluated multiplicative and additive interaction in logistic and Cox regression in clinical practices / 中华流行病学杂志

Conditional logistic regression analysis and unconditional logistic regression analysis are commonly used in case control study,but Cox proportional hazard model is often used in survival data analysis.Most literature only refer to main effect model,however,generalized linear model differs from general linear model,and the interaction was composed of multiplicative interaction and additive interaction.The former is only statistical significant,but the latter has biological significance.In this paper,macros was written by using SAS 9.4 and the contrast ratio,attributable proportion due to interaction and synergy index were calculated while calculating the items of logistic and Cox regression interactions,and the confidence intervals of Wald,delta and profile likelihood were used to evaluate additive interaction for the reference in big data analysis in clinical epidemiology and in analysis of genetic multiplicative and additive interactions.

Application of SAS macro to evaluated multiplicative and additive interaction in logistic and Cox regression in clinical practices / 中华流行病学杂志

Conditional logistic regression analysis and unconditional logistic regression analysis are commonly used in case control study,but Cox proportional hazard model is often used in survival data analysis.Most literature only refer to main effect model,however,generalized linear model differs from general linear model,and the interaction was composed of multiplicative interaction and additive interaction.The former is only statistical significant,but the latter has biological significance.In this paper,macros was written by using SAS 9.4 and the contrast ratio,attributable proportion due to interaction and synergy index were calculated while calculating the items of logistic and Cox regression interactions,and the confidence intervals of Wald,delta and profile likelihood were used to evaluate additive interaction for the reference in big data analysis in clinical epidemiology and in analysis of genetic multiplicative and additive interactions.

Analysis of environmental risk factors in congenital heart defects / 北京大学学报(医学版)

Objective:To explore the environmental risk factors of different categories of congenital heart defects ( CHD) and provide evidence for further risk factors and prevention research of CHD pheno-types. Methods:Data of Guangdong CHD Register Study from 2004 to 2012 were used. In the study, 3 038 CHD cases and 3 038 paired controls from 34 hospitals distributed in 17 cities were registered and related information were collected using uniform, and structured questionnaires. All the CHD phenotypes were coded according to the International Classification of Diseases 10th Revision (ICD-10) and classified into 6 categories according to their pathological features. Univariate analyses were adopted to filter poten-tial risk factors for each category of CHD. Then multivariate conditional Logistic regression was used to calculate the odds ratios of the risk factors for each category of CHD. Results:The risk factors for left-to-right shunt CHD included low ( OR=2 . 63 , 95%CI:2 . 04 -3 . 39 ) or over birth weight ( OR =2 . 21 , 95%CI:1 . 47-3 . 32 ) , premature delivery ( OR=1 . 95 , 95%CI:1 . 53-2 . 49 ) , polyembryony ( OR=1. 99, 95%CI: 1. 22 -3. 26), maternal low education, mother as factory worker (OR =1. 62, 95%CI:1 . 32-1 . 98 ) , parity≥2 ( OR =1 . 38 , 95%CI: 1 . 13 -1 . 69 ) , maternal abnormal reproduction history ( OR=2 . 29 , 95%CI:1 . 75-3 . 01 ) , fever ( OR=2 . 38 , 95%CI:1 . 26-4 . 48 ) , virus infection ( OR=1 . 80 , 95%CI:1 . 29 -2 . 51 ) , medicine usage ( OR=1 . 73 , 95%CI:1 . 11 -2 . 69 ) , passive smoking ( OR=1 . 69 , 95%CI:1 . 26-2 . 29 ) , chemical agent contact ( OR=8 . 71 , 95%CI:2 . 33 -32 . 58 ) , living in newly decorated houses ( OR=2 . 56 , 95%CI:1 . 60-4 . 09 ) or room close to the main road ( OR=1 . 40 , 95%CI:1 . 14-1 . 72 ) in the first 3 months of pregnancy and father as factory worker ( OR=1 . 46 , 95%CI:1 . 23-1 . 73 ) . The risk factors for pulmonary outflow tract obstruction CHD in-cluded low ( OR =5 . 98 , 95% CI: 2 . 88 -12 . 44 ) or over birth weight ( OR = 6 . 56 , 95% CI:1. 19-36. 26), maternal low education, parity≥2 (OR=2. 08, 95%CI:1. 03-4. 22), virus infection in the first 3 months of pregnancy ( OR =4 . 30 , 95%CI: 1 . 27 -13 . 45 ) . The risk factors for left ventricular outflow tract obstruction CHD included father as factory worker ( OR=6 . 01 , 95%CI:1 . 05-34. 59). The risk factors for transposition of the great arteries included low birth weight (OR=12. 93, 95%CI:1. 14-146. 26), maternal low education, mother as factory worker (OR=3. 69, 95%CI:1. 53-8. 91). The risk factors for conditions with intra cardiac mixing of oxygenated and deoxygenated blood in-cluded parity=2 ( OR=3 . 45 , 95%CI:1 . 42-8 . 38 ) . The risk factors for other CHD included over birth weight (OR=4. 87, 95%CI:1. 19-19. 94), maternal abnormal reproduction history (OR=2. 96, 95%CI:1. 14 - 7. 68 ), virus infection ( OR = 4. 92, 95% CI: 1. 56 - 15. 47 ), medicine usage (OR=4. 90, 95%CI:1. 22-19. 77) or passive smoking (OR=10. 31, 95%CI:1. 25-85. 05) in the first 3 months of pregnancy. Conclusion:The environmental risk factors were discrepant among different categories of CHD. Further risk factors study of CHD phenotypes should be performed specially. To prevent CHD, attention should be paid to the risk factors which are related to multi or complex categories of CHD.

Long term trends of blood lipid and glucose change in Guangzhou urban and rural natural population / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the long term trends of blood lipid and glucose change in Guangzhou urban and rural natural population.</p><p><b>METHODS</b>We cross-sectionally studied individuals 35 to 65 years of age (50% male) from People' Republic of China-United States cardiovascular and cardiopulmonary epidemiology research study using random sampling design in Guangzhou Shipyard and Panyu Dashi Town (Dashi Street and Luopu Street now) in 1983 and 1984 (n = 4 548), 1998 (n = 1 593), 2004 (n = 2 095)and 2011 (n = 1 692). Prevalence of dyslipidemia and pathoglycemia were standardized to the WHO world standard population. Blood lipid and glucose levels were compared in this cohort during the 28 years.</p><p><b>RESULTS</b>(1) The age adjusted mean average levels of blood lipid and glucose and the standardized prevalence rate of dyslipidemia and increased blood glucose as well as cardiovascular risk factors were significantly higher in the urban than in the rural residents and higher in male than in female participants (P < 0.01 or 0.05).(2) The age adjusted mean level of blood total cholesterol (TC), triglyceride (TG), glucose and high density lipoprotein cholesterol (HDL-C) increased from 1983/1984 to 2004 year in both urban and rural residents, and trended to be stable or decreased thereafter.(3) Standardized prevalence of multiple cardiovascular risk factors, such as high blood TG, low HDL-C, blood lipid disorder, fasting blood glucose level and diabetes, steadily increased from 1983/1984 to 2004 and this increasing trend was slowed or reversed thereafter, except the prevalence rate of high blood TC.</p><p><b>CONCLUSIONS</b>Except for high blood TC, the prevalence of multiple cardiovascular risk factors, such as high blood TG, low HDL-C, higher fasting blood glucose and diabetes, tended to be under control after 2004 in this cohort. Further efforts are warranted to strengthen this positive trend in the natural population.</p>

Sterilizing effect and residual bacteria of four different methods for sterilizing simple breathing vesicles / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effects of 4 different methods for disinfection of simple breathing vesicles and microbial residue.</p><p><b>METHODS</b>The disinfection tests were divided into 4 groups: G1 group (43 cases) with 500 mg/L chlorine dioxide spray, G2 group (28 cases) with alcohol spray, G3 group (47 cases) with 50 mg/L trichloroisocyanuric acid (TCCA) immersion, and G4 group (46 cases) with 50 mg/L chlorine dioxide solution immersion. After 30 min of disinfection, each group was examined by bacterial culture and colony count. The residual bacteria were identified and typed.</p><p><b>RESULTS</b>The 4 methods showed significant differences in bacterial colony count (P<0.001). The rate of bacterial residue was 0% in G1 group, 53.6% in G2 group, 27.7% in G3 group, and 21.7% in G4 group, showing significant differences between the 4 groups (P<0.001). The residual bacteria included antibiotic-resistant common opportunistic pathogen such as Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus haemolytic.</p><p><b>CONCLUSIONS</b>Disinfection with 500 mg/L chlorine dioxide spray is the best for simple breathing vesicles. Prolonged immersion in TCCA may lead to the growth of drug-resistant pathogens in the breathing vesicles.</p>