晚期非小细胞肺癌免疫检查点抑制剂新型生物标志物:血液PD-L1动态检测

背景免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)具有良好疗效已成为恶性肿瘤治疗领域备受瞩目的翘楚。然而,仅有小部分患者获得长期临床获益。如何选择生物标志物来筛查ICIs治疗优势人群仍是一大热点。方法收集51例晚期恶性肿瘤患者的肿瘤组织和配对血样本,进行PD-L1表达的相关性分析。40例晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者接受ICIs治疗,2个月时检测血液PD-L1(bloodPD-L1,bPD-L1)表达的动态变化,包括PD-L1 mRNA、外泌体PD-L1(exosomalPD-L1,exoPD-L1)蛋白和可溶性PD-L1(solublePD-L1,sPD-L1)。应用R软件计算最佳截断值,用于预测最佳客观缓解(best objective response,b OR)、无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)。结果51例不同恶性肿瘤患者中,组织PD-L1(tissuePD-L1,tPD-L1)表达阳性患者的PD-L1mRNA表达水平显著升高。40例接受ICIs治疗的晚期NSCLC患者中,bPD-L1 mRNA上调≥2.04的患者b OR、PFS和OS更佳;21例接受ICIs治疗的晚期NSCLC患者中,exoPD-L1上调≥1.86的患者临床获益更大。sPD-L1动态变化与ICIs疗效无显著相关性。PD-L1 mRNA和exoPD-L1联合检测更有利于预测ICIs治疗疗效。结论bPD-L1表达与tPD-L1表达存在正相关;晚期NSCLC患者ICIs治疗初期PD-L1 mRNA和(或)exoPD-L1表达升高,可作为评估临床获益的新型生物标志物。

Long-term follow-up of abdominal aortic balloon occlusion for the treatment of pernicious placenta previa with placenta accreta

Objective:To evaluate the efficacy and safety of balloon occlusion of the abdominal aorta for the treatment of pernicious placenta previa with placenta accreta.Methods:The clinical data of 623 patients with pernicious placenta previa combined with placenta accrete,who were admitted to our hospital from January 2013 to January 2019 were retrospectively analyzed.All patients underwent abdominal aortic balloon occlusion combined with cesarean section,and 78 patients underwent sequential bilateral uterine artery embolization.We analyzed the operation time,intraoperative blood loss,blood transfusion volume,intraoperative and postoperative complications,fetal radiation exposure time and dose,and the Apgar score of the newborns.We also performed other evaluations to ascertain the efficacy and safety of abdominal aortic balloon occlusion treatment for dangerous placenta previa with placenta accrete.Results:Of the 623 patients,545 underwent only abdominal aortic balloon occlusion,and 78 underwent uterine artery embolization due to intraoperative or postoperative bleeding.The uterus was successfully preserved in all patients.Except for five cases of right lower extremity arterial thrombosis,the remaining patients did not have postoperative lower extremity arteriovenous thrombosis,renal insufficiency,late postpartum hemorrhage,ectopic embolism,spinal cord or peripheral nerve damage,pelvic infection,or other serious complications.The mean operative time was 65.3(±14.5)min.The mean intraoperative blood loss was620(±570)ml.Ninety-six patients(15.4%,96/623)were treated with blood transfusion,and the average amount of blood transfused was 750(±400)ml.The average number of hospitalization days was 6.8(±3.4)days,the average time of fetal ray exposure was 5.2(±1.6)s,and the average radiation dose was 4.1(±2.7)m Gy.The neonatal Apgar score,was 8.4(±0.6)points at 1 min,and 9.6(±0.4)points at 5 min.In the follow-up to May 31,2019,29 patients were lost to follow-up,96 were lactating,and 498 were menstruating.Except for the cases lost to follow-up,the remaining 596 surviving newborns(including 2 twins)showed no abnormalities at the 42-day postnatal outpatient follow-up examination.Conclusion:Balloon occlusion of the abdominal aorta is a safe and effective method for the treatment of pernicious placenta previa with placenta accreta.

Risk Factors for Gestational Diabetes Mellitus(GDM)in Subsequent Pregnancy Among Women Without GDM History in China:A Multicenter Retrospective Study

Objective:This study aimed to determine the likelihood of gestational diabetes mellitus(GDM)in subsequent pregnancy among women without GDM history and to identify risk factors for GDM in subsequent pregnancy.Methods:This retrospective cohort study involved participants who delivered twice in same hospital of 18 research centers when delivered the second baby from January 2018 to December 2018.Finally 6204 women were enrolled and 5180 women without GDM history were analyzed further.Women were categorized as non-GDM or GDM based on the blood glucose values of the subsequent pregnancy,and the characteristics and GDM risk of these groups were compared.A univariate analysis of potential risk factors was performed using the Chi-squared test and/ort-test for qualitative or quantitative variables,respectively.Associations withP values<0.1 were chosen to be included in the multivariate binary logistic regression model.Results:In primary analysis of 6204 women,the incidence of GDM in subsequent pregnancy is 48.9%(490/1002)in women with GDM history and 16.1%(835/5202)in women without GDM history.In a further analysis for 5180 women without GDM at index pregnancy,compared with the non-GDM group,the GDM group had a significantly higher age,prepregnancy body mass index,and blood glucose value at each oral glucose tolerance test(OGTT)timepoint(fasting,1 h and 2 h)during the index and subsequent pregnancies,as well as higher weight retention during the interval between the two pregnancies(P<0.001).Age above 35 years in subsequent pregnancy(odds ratio(OR)=1.540,95%confidence interval(CI)=1.257-1.886,P<0.001),macrosomia in index pregnancy(OR=1.749,95%CI=1.277-2.395,P=0.001),OGTT blood glucose values in index pregnancy(fasting,OR=2.487,95%CI=1.883-3.285,P<0.001;1 h,OR=1.142,95%CI=1.051-1.241,P=0.002;2 h,OR=1.290,95%CI=1.162-1.432,P<0.001)and weight retention(OR=1.052,95%CI=1.035-1.068,P<0.001)were independent risk factors for GDM in subsequent pregnancy.Conclusion:For women without GDM history,GDM risk factors including age,macrosomia history,OGTT value,and weight retention,these can be evaluated before a subsequent pregnancy.Early warning and interventions are needed for women at high risk.

Intra-abdominal aortic balloon occlusion in the management of placenta percreta

Background:Massive bleeding is the main concern for the management of placenta percreta(PP).Intra-abdominal aortic balloon occlusion(IABO)is one method for pelvic devascularization,but the efficacy of IABO is uncertain.This study aims to investigate the outcomes of IABO in PP patients.Methods:We retrospectively reviewed the clinical data of PP cases from six tertiary centers in China between January 2011 and December 2015.PP cases with/without the use of IABO were analyzed.Propensity score matching analysis was performed to reduce the effect of selection bias.Postpartum hemorrhage(PPH)and the rate of hysterectomy,as well as neonatal outcomes,were analyzed.Results:One hundred and thirty-two matched pairs of patients were included in the final analysis.Compared with the control group,maternal outcomes,including PPH(68.9%vs.87.9%,χ^(2)=13.984,P<0.001),hysterectomy(8.3%vs.65.2%,χ^(2)=91.672,P<0.001),and repeated surgery(1.5%vs.12.1%,χ^(2)=11.686,P=0.001)were significantly reduced in the IABO group.For neonatal outcomes,Apgar scores at 1 minute(8.67±1.79vs.8.53±1.68,t=-0.638,P=0.947)and 5 minutes(9.43±1.55vs.9.53±1.26,t=0.566,P=0.293)were not significantly different between the two groups.Conclusions:IABO can significantly reduce blood loss,hysterectomies,and repeated surgeries.This procedure has not shown harmful effects on neonatal outcomes.

Prevalence and characteristics of macrosomia in the first and subsequent pregnancy: a multi-center retrospective study

To the Editor:Macrosomia is of growing prevalence and concern worldwide.In China,there has been a marked increase in the prevalence of macrosomia over the past few decades as a result of economic development and improvements in living standards.

Risk Factors and Pregnancy Outcome in Women with a History of Cesarean Section Complicated by Placenta Accreta

Objective:To explore the risk factors and pregnancy outcomes in women with a history of cesarean section complicated by placenta accreta(PA).Methods:This case-control study included clinical data from singleton mothers with a history of cesarean section in 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017.According to the intraoperative findings after delivery,the study population was divided into PA and non-PA groups.We compared the pregnancy outcomes between the two groups,used multivariate logistic regression to analyze the risk factors for placental accreta.Results:For this study we included 11,074 pregnant women with a history of cesarean section;and of these,869 cases were in the PA group and 10,205 cases were in the non-PA group.Compared with the non-PA group,the probability of postpartum hemorrhage(236/10,205,2.31%vs.283/869,32.57%),severe postpartum hemorrhage(89/10,205,0.87%vs.186/869,21.75%),diffuse intravascular coagulation(3/10,205,0.03%vs.4/869,0.46%),puerperal infection(33/10,205,0.32%vs.12/869,1.38%),intraoperative bladder injury(1/10,205,0.01%vs.16/869,1.84%),hysterectomy(130/10,205,1.27%vs.59/869,6.79%),and blood transfusion(328/10,205,3.21%vs.231/869,26.58%)was significantly increased in the PA group(P<0.05).At the same time,the neonatal birth weight 3250.00(2950.00–3520.00)g vs.2920.00(2530.00–3250.00)g),the probability of neonatal comorbidities(245/10,205,2.40%vs.61/869,7.02%),and the rate of neonatal intensive care unit admission(817/10,205,8.01%vs.210/869,24.17%)also increased significantly(P<0.05).Weight(odds ratio)(OR)=1.03,95%confidence interval(CI):1.01–1.05)),parity(OR=1.18,95%CI:1.03–1.34),number of miscarriages(OR=1.31,95%CI:1.17–1.47),number of previous cesarean sections(OR=2.57,95%CI:2.02–3.26),history of premature rupture of membrane(OR=1.61,95%CI:1.32–1.96),previous cesarean-section transverse incisions(OR=1.38,95%CI:1.12–1.69),history of placenta previa(OR=2.44,95%CI:1.50–3.96),and the combination of prenatal hemorrhage(OR=9.95,95%CI:8.42–11.75)and placenta previa(OR=91.74,95%CI:74.11–113.56)were all independent risk factors for PA.Conclusion:There was an increased risk of adverse outcomes in pregnancies complicated by PA in women with a history of cesarean section,and this required close clinical attention.Weight before pregnancy,parity,number of miscarriages,number of previous cesarean sections,history of premature rupture of membranes,past transverse incisions in cesarean sections,a history of placenta previa,prenatal hemorrhage,and placenta previa were independent risk factors for pregnancies complicated with PA in women with a history of cesarean section.These independent risk factors showed a high value in predicting the risk for placentab accreta in pregnancies of women with a history of cesarean section.

Bladder Bleeding Due to Placenta Percreta:Report of Four Cases and Management Discussion

Placenta percreta with bladder bleeding can occur during gestation or postpartum,posing a great threat to both mother and fetus.But it is rare and lacks standard management strategies.We reported four cases suffering from bladder bleeding caused by placenta percreta even with hemorrhagic shock admitted between January 1^(st),2011 and December 31^(th),2020 in The First Affiliated Hospital of Zhengzhou University.Clinical information,including age,gravidity and parity,ultrasound and magnetic resonance imaging manifestations,onset gestational age,bladder bleeding volume,clinical manifestations under bleeding,diagnosis,hemostatic methods,hospital stay,treatment cost,and prognosis,are presented.Two cases had bladder bleeding during the second trimester,respectively on the 22^(+3)and 23^(+5)weeks.Pregnancy was terminated timely.The other two cases had bladder bleeding on the 2nd day post near-term cesarean section when activity.All the four cases achieved successful hemostasis following angiography and concomitant embolization for iliac vessels,and one of them received electrocoagulation hemostasis under cystoscopy,but failed.They all had favorable clinical outcomes and had no long-term complications.The neonatal outcome in the two cases that bladder hemorrhage occurred after near-term c-section was good.The newborns did not survive in two cases in which bladder hemorrhage occurred at the second trimester of pregnancy.Timely termination of pregnancy is recommended when such a condition develops during gestation.Diagnosis of bladder bleeding is relatively easy,for it is characterized by fast speed and large volume,with concomitant distension of the lower abdomen,blood discharge from the urethral orifice,or the indwelling catheter.Interventional embolization is an effective means to treat bladder bleeding caused by placenta percreta,while electrocoagulation hemostasis under cystoscopy must be applied with great caution.For the pregnant women with a high risk of placenta percreta,timely and accurate diagnosis should be achieved during the gestational age,and bladder bleeding should be concerned when placenta penetrates through the anterior wall of uterus.