Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Baryon Electric Charge Correlation as a Magnetometer of QCD.

The correlation between net baryon number and electric charge, χ_{11}^{BQ}, can serve as a magnetometer of QCD. This is demonstrated by lattice QCD computations using the highly improved staggered quarks with physical pion mass of M_{π}=135 MeV on N_{τ}=8 and 12 lattices. We find that χ_{11}^{BQ} along the transition line starts to increase rapidly with magnetic field strength eB≳2M_{π}^{2} and by a factor 2 at eB≃8M_{π}^{2}. Furthermore, the ratio of electric charge chemical potential to baryon chemical potential, µ_{Q}/µ_{B}, shows significant dependence on the magnetic field strength and varies from the ratio of electric charge to baryon number in the colliding nuclei in heavy ion collisions. These results can provide baselines for effective theory and model studies, and both χ_{11}^{BQ} and µ_{Q}/µ_{B} could be useful probes for the detection of magnetic fields in relativistic heavy ion collision experiments as compared with corresponding results from the hadron resonance gas model.

Theoretical Study on Ethylamine Dissociation Reactions Using VRC-VTST and SS-QRRK Methods.

Barrierless bond dissociation reactions play an important role in fuel combustion. In this work, the pressure-dependent dissociation rate constants of ethylamine (EA) are accurately determined using variable-reaction-coordinate variational transition-state theory combined with the system-specific quantum Rice-Ramsperger-Kassel method. Before the kinetics calculations, the performances of four density functional theory methods in describing the bond dissociation of EA are evaluated against the benchmark method, FIC-MRCISD(T)+Q/cc-pVTZ, and the MN15-L/cc-pVTZ method is the best choice. By comparison of the Gibbs free energies and the rate constants for the bond dissociation reactions of EA, ethanol, and propane, the influence of functional groups on the reaction kinetics is discussed. The kinetics calculations show that the dissociation rate constants of EA are sensitive to pressure at low pressures and high temperatures, and the dominant channel is the reaction that yields C2H5 and NH2 radicals. A literature combustion model of EA is updated with our calculations, and the satisfactory agreement between the model predictions and reported ignition delay times of EA suggests the reliability of our calculations.

[Clinical characteristics and surgical outcomes of pediatric epiretinal membranes without specific etiologies].

Objective: To describe clinical characteristics and surgical outcomes of pediatric epiretinal membranes (ERMs) without specific etiologies. Methods: Medical data of a cohort of pediatric patients (≤14 years) who had ERMs without specific etiologies, underwent surgical removal from January 2019 to September 2021, and were followed up for at least 12 months were retrospectively reviewed. Age at presentation, chief complaints, color fundus photographs, optical coherence tomographic images, preoperative and postoperative visual acuities, anatomical changes, and postoperative complications were assessed. Results: There were 14 patients (17 eyes), including 5 females (6 eyes) and 9 males (11 eyes). The mean age at surgery was 6.31±2.91 years, and the follow-up duration was 17.3±9.5 months. Eight patients were found to have low vision in the school physical examination. Fifteen eyes had an appearance of cellophane macular reflex on fundus images. On optical coherence tomographic images, 10 eyes had"taco"folds, and 7 eyes had"ripple"folds. Five eyes had ellipsoid zone disruptions, while 12 eyes had ellipsoid zone integrity. The preoperative and postoperative best-corrected visual acuities in logMAR were 0.532±0.302 and 0.340±0.298. One patient suffered traumatic cataract and secondary retinal detachment postoperatively, and after further vitrectomy, the retina became attached. Conclusion: Pediatric ERMs without specific etiologies were mostly found in school-age children with cellophane macular reflex and"taco"folds. Vitrectomy may result in both potential visual acuity and macular anatomical improvements.

[The distribution of blood pressure and associated factors of the elderly with type 2 diabetes in Jiangsu Province].

Objective: To investigate the distribution of blood pressure and analyze the associated factors of blood pressure of the elderly with type 2 diabetes in Jiangsu Province. Methods: The elderly over 60 years old participants with type 2 diabetes in the communities of Huai'an City and Changshu City, Jiangsu Province were selected in this study. They were divided into two groups: taking antihypertensive drugs and not taking antihypertensive drugs. The demographic characteristics, such as age and sex, and relevant factors were collected by questionnaire. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by physical examination. The percentile of SBP and DBP in each age group of men and women were described. The kernel density estimation curve was used to show the blood pressure distribution. The trend of blood pressure with age was fitted by locally weighted regression. The logistic regression model was used to analyze relevant factors of blood pressure. Results: A total of 12 949 participants were included in this study, including 7 775 patients in the antihypertensive drug group and 5 174 patients in the group without antihypertensive drugs. The SBP of participants was concentrated at 140-160 mmHg, and their DBP was concentrated at 75-85 mmHg. There were significant differences in the distribution of blood pressure among the subgroups of body mass index (BMI) and rural areas whether taking antihypertensive drugs and not. For participants aged under 80 years old, the SBP showed an increasing trend with age and the DBP showed a decreasing trend with age. Age, BMI ≥24 kg/m2, fasting blood glucose ≥7.0 mmol/L, living in rural areas and no smoking were influencing factors of the elevated SBP; BMI ≥24 kg/m2, male, living in rural areas, no smoking, drinking alcohol and not receiving drug hypoglycemic treatment were influencing factors of the elevated DBP. Conclusion: The SBP of older diabetic adults in Jiangsu Province is at a high level, and the distribution of blood pressure is significantly different between men and women in taking antihypertensive drugs group. The SBP presents a rising trend and the DBP is decreasing at the age of 60-80 years. The blood pressure level of this population are mainly affected by age, BMI, urban and rural areas, smoking.

[Analysis of incidence and associated factors of preterm birth based on pre-pregnancy body mass index stratification].

Objective: To analyze the incidence of preterm birth based on pre-pregnancy body mass index (BMI) stratification and explore the associated factors of preterm birth among pregnant women at different BMI stratifications. Methods: From February 2018 to December 2020, pregnant women who participated in China Birth Cohort Study (CBCS) and gave birth at Beijing Obstetrics and Gynecology Hospital were enrolled as the study subjects. Electronic Data Capture System and standard structured questionnaires were used to collect data related to pre-pregnancy, pregnancy, and delivery for pregnant women. Pregnant women were divided into the low-weight group, normal-weight group and overweight group based on their pre-pregnancy BMI. A Cox proportional hazards model was used to analyze the associated factors of preterm birth among pregnant women with different BMI before pregnancy. Results: A total of 27 195 singleton pregnant women were included, with a preterm birth rate of 5.08% (1 381/27 195). The preterm birth rates in the low-weight group, normal-weight group and overweight group were 4.29% (138/3 219), 4.63% (852/18 390) and 7.00% (391/5 586) respectively (P<0.001). After adjusting for relevant factors, the Cox proportional hazards model showed that the risk of preterm birth in the overweight group was 1.457 times higher than that in the normal-weight group (95%CI: 1.292-1.643). Preeclampsia-eclampsia (HR=2.701, 95%CI: 1.318-5.537) was the associated factor for preterm birth in the low-weight group. Advanced maternal age (HR=1.232, 95%CI: 1.054-1.441), history of preterm birth (HR=4.647, 95%CI: 3.314-6.515), vaginal bleeding in early pregnancy (HR=1.613, 95%CI: 1.380-1.884), and preeclampsia-eclampsia (HR=3.553, 95%CI: 2.866-4.404) were associated factors for preterm birth in the normal-weight group. Advanced maternal age (HR=1.473, 95%CI: 1.193-1.818), history of preterm birth (HR=3.209, 95%CI: 1.960-5.253), vaginal bleeding in early pregnancy (HR=1.636, 95%CI: 1.301-2.058), preeclampsia-eclampsia (HR=2.873, 95%CI:2.265-3.643), and pre-gestational diabetes mellitus (HR=1.867, 95%CI: 1.283-2.717) were associated factors for preterm birth in the overweight group. Conclusion: Pre-pregnancy overweight is an associated factor for preterm birth, and there are significant differences in the associated factors of preterm birth among pregnant women with different BMI before pregnancy.

[Association between coagulation function indicators and placental abruption among preeclampsia-eclampsia pregnant women].

Objective: To explore the association between coagulation function indicators and placental abruption (PA) in different trimesters of pregnancy among preeclampsia-eclampsia pregnant women. Methods: From February 2018 to December 2020, pregnant women who participated in the China birth cohort study and were diagnosed with preeclampsia, eclampsia and chronic hypertension with superimposed preeclampsia in Beijing Obstetrics and Gynecology Hospital were enrolled in this study. The baseline and follow-up information were collected by questionnaire survey, and the coagulation function indicators in the first and third trimesters were obtained through medical records. The Cox proportional hazards model was used to analyze the association between the coagulation function indicators and PA. A restrictive cubic spline curve was used to draw the dose-response curve between the relevant coagulation function indicators and PA. Results: A total of 1 340 participants were included in this study. The age was (32.50±4.24) and the incidence of PA was 4.4% (59/1 340). After adjusting for relevant factors, Cox proportional hazards model showed that compared with the high-level classification of fibrinogen (FIB), participants within the middle-(HR=3.28, 95%CI: 1.27-8.48) and low-level (HR=3.84, 95%CI: 1.40-10.53) classification during the first trimester and within the low-level classification (HR=4.18, 95%CI: 1.68-10.39) during the third trimester were more likely to experience PA. Compared with the middle-level classification of pro-thrombin time (PT), the risk of PA in the participants within the low-level classification (HR=2.67, 95%CI: 1.48-4.82) was significantly higher in the third trimester. The restrictive cubic spline analysis showed a linear negative association between FIB and PA in the first and third trimesters, while PT and PA showed an approximately L-shaped association. Conclusion: Among pregnant women diagnosed with preeclampsia-eclampsia, the middle-and low-level classification of FIB in the first and third trimesters and the low-level classification of PT in the third trimester could increase the risk of PA.

[A preliminary study on the prevention of hemorrhage after laparoscopic pancreaticoduodenectomy by wrapping gastroduodenal artery stump in the left external liver lobe and the left caudate lobe].

Objective: To investigate the safety and efficacy of embedding the stump of gastroduodenal artery between the left lateral lobe of the liver and the left caudate lobe to prevent bleeding after laparoscopic pancreaticoduodenectomy. Methods: The clinical data of 41 patients who underwent laparoscopic pancreaticoduodenectomy at the second Hospital of Hebei Medical University from October 2021 to April 2022 were analyzed retrospectively.There were 27 males and 14 females, aged (63.0±9.2)years (range: 48 to 78 years), and the body mass index was (24.1±3.2)kg/m2 (range: 15.4 to 31.6 kg/m2). After routine laparoscopic pancreaticoduodenectomy, the stump of gastroduodenal artery was embedded between the left lateral lobe and the left caudate lobe of the liver, and the hepatic parenchyma of the left lateral lobe and the left caudate lobe were sutured with absorbable sutures.The occurrence and recovery of postoperative complications (pancreatic fistula, biliary fistula, postoperative abdominal bleeding, abdominal infection, liver abscess) were observed. Results: All the operations of 41 patients were completed successfully.The operation time was (277.5±52.0) minutes (range: 192 to 360 minutes). The entrapment time of gastroduodenal artery stump was (3.1±0.6) minutes (range: 2.3 to 4.2 minutes), and the intraoperative blood loss (M(IQR)) was 300 (200) ml (range: 50 to 800 ml).The results of ultrasound examination of hepatic artery on the first day after operation showed that the blood flows of hepatic artery were unobstructed.Postoperative pancreatic fistula occurred in 3 cases, including grade B pancreatic fistula in 2 cases (1 case with abdominal infection) and biochemical leakage in 1 case. Three patients with pancreatic fistula were discharged successfully after continuous abdominal drainage. There was no biliary fistula, abdominal bleeding, abdominal infection, liver abscess or postoperative liver dysfunction. Conclusion: The encasement of the gastroduodenal artery stump by the left outer and left caudate lobes of the liver may be an effective way to prevent bleeding from the rupture of the gastroduodenal artery stump after laparoscopic pancreatoduodenectomy, which is easy and safe to perform.

Modification of Enteromorpha prolifera with dielectric barrier discharge plasma to enhance malachite green adsorption.

Dyes, a kind of visible chemical, have severe deleterious effects on human health and ecological environment. In this work, batch biosorption experiments were carried out under various experimental conditions such as pH value and agitation time to optimize the potentiality of Enteromorpha prolifera for the removal of malachite green (MG) dye from aqueous solution (70·7%). Then, the algal biomass was treated with a dielectric barrier discharge (DBD) in helium for 4 and 10 min to enhance MG removal efficiency (84·7 and 96·6%). In addition, Fourier-transform infrared spectroscopy in combination with scanning electron microscopy was employed to monitor the chemical and physical changes of algal cells treated by DBD. This study illustrates that DBD may serve as an effective tool to activate the functional groups on the cell wall surface for dye binding, and it even offers an alternative new technique to improve the adsorption properties of native biosorbents for the removal of toxic dyes from wastewater.

[Clinical characteristics and prognosis of 46 patients with macrofocal multiple myeloma].

The clinical characteristics, laboratory results, response to treatment, and prognosis of 46 macrofocal multiple myeloma(MFMM) patients at our center from January 2013 to December 2019 were analyzed retrospectively. The other 92 patients were selected as matched-controls based on diagnostic period and treatment. Among the 1 137 MM patients, 46 patients met the definition criteria of MFMM (4.0%), with median age 56 years, which was not statistically different from whole MM population (P=0.066). According to the international staging system (ISS) and Revised ISS, the proportion of patients with advanced stage in MFMM group was less common than that of controls (P<0.05). More plasmacytomas in MFMM patients were presented (43.5% vs. 18.5%, P<0.05). Regarding cytogenetic abnormalities, there were minor patients manifesting high-risk features in MFMM group (15.8% vs. 32.2%, P=0.058). Translocation(11;14) could be detected in 32.4% MFMM patients and 9.4% typical myeloma patients (P<0.05). The treatment regimens were comparable. As to the best response of treatment, the complete response (CR) rate in MFMM group was significantly higher than that of controls (78.3% vs. 60.9%, P<0.05). The median follow-up time was 37.9 months. The median progression-free survival in MFMM and control groups were 77.5 vs. 39.8 months, respectively (P<0.05). The overall survival (OS) of MFMM patients was significantly longer (not reached vs. 68.2 months, P<0.05).

[Efficacy and prognosis of newly diagnosed multiple myeloma patients treated with bortezomib, lenalidomide and dexamethasone].

Objective: To evaluate the efficacy of VRD (bortezomib+lenalidomide+dexamethasone) in newly diagnosed multiple myeloma (NDMM) patients as well as the effect of the regimen on the long-term prognosis. Methods: The clinical characteristics, survival rates, response rates and minimal residual disease (MRD) of patients with NDMM at Institute of Hematology & Blood Diseases Hospital from January 1, 2013 to January 1, 2020 were retrospectively analyzed. Subgroup analysis was also performed among groups according to the cytogenetics and autologous stem cell transplantation (ASCT) of patients. Results: A total of 87 patients were retrospectively analyzed. The age[M(Q1,Q3)] of all patients was 56 (51, 61) years and males and females accounted for 58.6% (51/87) and 41.4% (36/87), respectively. The overall response rate (ORR) was 95.9% (71/74) after 2 courses of induction therapy, with 13.5% (10/74) achieving the deep response [complete response (CR) or better] and 51.3% (38/74) of patients achieving a very good partial response (VGPR) or better. After 4 courses of induction therapy, the ORR achieved 95.2% (60/63), and the proportions of the deep response and VGPR or better grew up to 46.0% (29/63) and 77.7% (49/63). According to the treatment, the patients (≤65 years old) were divided into transplantation group and non-transplantation group. After the induction therapy, 88.8% (32/36) of patients in the transplantation group achieved VGPR or better, and 55.5% (20/36) reached the deep response. After the transplantation, the proportion increased to 97.1% (34/35) and 77.2% (27/35), respectively(88.8% vs 97.1%,P=0.174;55.5% vs 77.2%,P=0.055), with the rate of undetectable MRD increasing from 44.4% (16/36) to 77.8% (28/36) (P=0.004). In the non-transplantation group, 74.2% (23/31) of patients achieved VGPR or better after 4 courses of induction therapy, 35.5% (11/31) of the patients achieved deep response and the rate of undetectable MRD was 37.0% (10/27). Compared with the non-transplantation group, transplantation was associated with a higher rate of complete response (89.5% vs 53.1%, P<0.001) and a lower rate of MRD detection(78.4% vs 55.2%, P=0.045). The median follow-up time of all patients was 26.3 months (20.8, 33.8). The median progression-free survival and overall survival were not reached. The three-year PFS and OS rates were 78.4% and 87.2%, respectively. None of the standard-risk group, the high-risk group, the transplantation group and non-transplantation group achieved the median PFS and OS. Conclusions: VRD regimen has a promising efficacy and results in a substantial survival benefit. ASCT after VRD induction therapy is associated with higher rate of deep response, higher rate of undetectable MRD and longer survival.

[Early warning of low maternal unconjugated estriol level by prenatal screening for fetus with X-linked ichthyosis].

Objective: To analyze the characteristic of prenatal serological screening in fetus with X-linked ichthyosis (XLI), and to explore the relationship between unconjugated estriol (uE3) levels and XLI. Methods: A total of 56 fetuses with Xp22.31 microdeletion indicated by prenatal diagnosis and 70 fetuses diagnosed with trisomy 21 and 26 fetuses with trisomy 18 in Henan Provincial People's Hospital and Affiliated Hospital of Weifang Medical College from September 2016 to June 2021 were collected. The multiples of median (MoM) values of uE3, alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) during the second trimester of pregnancy were retrospectively analyzed. Prenatal diagnosis was made by amniotic fluid karyotype analysis and genome copy number variant analysis, parent genetic verification and pathogenicity analysis were performed, and maternal and infant outcomes were followed up. Results: Of 56 pregnant women with fetal Xp22.31 microdeletion, 43 underwent serological screening during the second trimester of pregnancy, of which 42 were abnormal (39 male fetuses and 3 female fetuses). The median uE3 MoM value of 39 male fetuses [0.06 (0.00-0.21)] was lower than the normal value and significantly lower than that of fetuses with trisomy 21 [0.71 (0.26-1.27)] and fetuses with trisomy 18 [0.36 (0.15-0.84)], the difference was statistically significant (Z=99.96, P<0.001). While the MoM values of AFP and hCG were all within the normal range. Among the 56 fetuses carrying Xp22.31 microdeletion, 45 were male fetuses and 11 were female fetuses, and the deletion fragments all involved STS gene. Eighty-nine percent (50/56) were inherited from mother (49 cases) or father (1 case), and 11% (6/56) were de novo mutations. Follow-up showed 48 live births (38 males and 10 females) and 8 chose to terminate pregnancy (7 males and 1 female). Among the 38 male newborns, 37 presented with scaly skin changes from 1 to 3 months of age, and one had no clinical manifestations until 4 months after birth. Ten female newborns had no obvious clinical manifestations. Conclusions: The decrease levels of uE3 MoM on maternal serological screening is closely related to the higher risk of XLI in male fetuses. For pregnant women with low uE3 in serological screening or with family history of ichthyosis, in addition to chromosomal karyotype analysis, joint detection of genomic copy number variant analysis should be recommended.

[SMARCA4-deficient undifferentiated carcinoma of the gastrointestinal tract: a clinicopathological and immunohistochemical study of nine cases].

Objective: To investigate the clinicopathological features, immunophenotype and differential diagnoses of SMARCA4-deificient undifferentiated carcinoma (SMARCA4-DUC) of the gastrointestinal tract. Methods: The clinicopathological data and immunohistochemical profiles of nine cases of SMARCA4-DUC of the gastrointestinal tract diagnosed in Fudan University Shanghai Cancer Center, from 2018 to 2021, were analyzed retrospectively. The relevant literature was reviewed. Results: There were seven males and two females with age at presentation ranging from 39 to 74 years (mean 58 years, median 64 years). The tumor occurred in the stomach (6 cases), right hemicolon (2 cases) and duodenum (1 case). The main symptoms included dysphagia, abdominal pain, diarrhea and melena. Five cases were resected, and the tumor sizes ranged from 5.0 to 8.7 cm (mean 6.7 cm). Microscopically, the tumor was composed of sheets of undifferentiated round to epithelioid cells with large vesicular nuclei harboring prominent nucleoli and displaying brisk mitotic activity. Foci of dyscohesive rhabdoid cells were also noted. The tumor cells were generally uniform; however, prominent pleomorphism and spindle cell component was present in one case each. Five cases contained areas of coagulative necrosis, and one case showed myxoid change of the stroma. By immunohistochemistry, eight cases showed complete loss of BRG1 (SMARCA4) and BRM (SMARCA2) expression. Whereas the expression of these two markers was lost in the epithelioid component of one case, it remained in the spindle cell component (mosaic pattern). Apart from one case with partial expression of pan-cytokeratin, all other eight cases showed either limited (<5%, n=5) or totally negative (n=3) staining of pan-cytokeratin. In addition, four cases also expressed CD34, SOX2 and SALL4. Six patients had follow-up data: four died of disease within 1 year. Conclusions: SMARCA4-DUC of the gastrointestinal tract represents a highly aggressive malignancy with poor outcome. Due to lack of cell-specific differentiation, it is not uncommonly misdiagnosed as a wide variety of poorly-differentiated or undifferentiated tumors. Increased recognition of this rare but distinctive entity not only facilitates the diagnosis and differential diagnosis, but also provides important therapeutic and prognostic information for the clinicians.

[Tuberculosis presenting as gastrointestinal perforation and large confluent pulmonary cavities: a case report].

We report an unusual case presented as acute gastrointestinal perforation and large confluent pulmonary cavities. A 23-year-old male was admitted to the emergency department with complaints of abdominal pain for 1 month, which exacerbated for 1 day. He also reported a 3-month history of diarrhea and productive cough. Computed tomography (CT) scan showed multiple large confluent cavities in the lung, along with massive free gas in the abdomen suggesting gastrointestinal perforation. Exploratory laparotomy was performed and affected bowel segment was resected. His sputum examination was positive for both acid-fast staining and Mycobacterium tuberculosis complex gene (Xpert) testing. Pathology of small intestine revealed micro-abscess formation and was positive for acid-fast bacilli. A final diagnosis of pulmonary tuberculosis and intestinal tuberculosis was made.

[Application of branch-first technique in total thoracic aorta replacement: short and medium term effect of 11 cases].

Objective: To examine the short and medium term effect of branch-first technique in total thoracic aorta replacement. Methods: The clinical data of eleven patients with ascending aortic aneurysms or type A aortic dissection+Crawford Ⅰ or Ⅱ total thoracoabdominal aortic aneurysm who were treated at Department of Cardiovascular Surgery in Henan Province Chest Hospital from January 2018 to July 2021 were retrospectively analyzed. There were 7 males and 4 females, aging (38±5) years (range: 28 to 45 years), 7 cases of whom were diagnosed with Marfan syndrome, 1 case was diagnosed with coarctation of aorta. Operations were performed under mild hypothermic and branch-first technique. Firstly, the middle and small incision in the chest was combined with the 6th intercostal incision in the left posterior lateral side. Secondly, four branches artificial blood vessels were anastomosed with the brachiocephalic artery to ensure the blood supply to the brain. After the circulation was blocked, intracardiac and aortic proximal operations were performed. Intercostal artery reconstruction and thoracic descending aorta replacement were completed after opening circulation. Results: The operative time of this group was (645.9±91.7) minutes (range: 505 to 840 minutes). One case had cerebral infarction and 1 case had chylothorax. The patients were followed up 4 to 47 months, 1 patient underwent thoracic and abdominal aorta+iliac artery resection and replacement due to the progression of abdominal aortic aneurysm 3 months after operation. Intercostal artery obstruction occurred in 2 cases, and the rest lived well. Conclusions: One-stage whole thoracic aorta replacement with branch-first technique has satisfactory results in the short and medium term, with no risk of residual aortic aneurysm rupture. It is an effective treatment for young and organs function well patients with complex aortic lesions.

[Impact of bicuspid aortic valve or tricuspid aortic valve on hemodynamics and left ventricular reverse remodeling in patients after transcatheter aortic valve replacement].

Objective: To compare the impact of bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) on hemodynamics and left ventricular reverse remodeling after transcatheter aortic valve replacement (TAVR). Methods: We retrospectively analyzed the clinical data of patients who underwent TAVR in our hospital from January 2019 to March 2021. Patients were divided into BAV group and TAV group according to aortic contrast-enhanced CT. Each patient was followed up by N-terminal pro B-type natriuretic peptide (NT-proBNP) and echocardiography at four time points, namely before TAVR, 24 hours, 1 month and 6 months after TAVR. Echocardiographic data, including mean pressure gradient (MPG), aortic valve area (AVA), left ventricular ejection fraction (LVEF), left ventricle mass (LVM) and LV mass index (LVMi) were evaluated. Results: A total of 41 patients were included. The age was (75.0±8.6) years, and male patients accounted for 53.7%. There were 19 BAV patients and 22 TAV patients in this cohort. All patients undergoing TAVR using a self-expandable prosthesis Venus-A valve. MPG was (54.16±21.22) mmHg(1 mmHg=0.133 kPa) before TAVR, (21.11±9.04) mmHg at 24 hours after TAVR, (18.84±7.37) mmHg at 1 month after TAVR, (17.68±6.04) mmHg at 6 months after TAVR in BAV group. LVEF was (50.42±13.30)% before TAVR, (53.84±10.59)% at 24 hours after TAVR, (55.68±8.71)% at 1 month after TAVR and (57.42±7.78)% at 6 months after TAVR in BAV group. MPG and LVEF substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05) in BAV group. MPG in TAV group improved at each time point after operation, and the difference was statistically significant (all P<0.05). LVMi was (164.13±49.53), (156.37±39.11), (146.65±38.84) and (134.13±39.83) g/m2 at the 4 time points and the value was significantly reduced at 1 and 6 months post TAVR compared to preoperative level(both P<0.05). LVEF in the TAV group remained unchanged at 24 hours after operation, but it was improved at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). LVMi in TAV group substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05). NT-proBNP in both two groups improved after operation, at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). MPG in TAV group improved better than in BAV group during the postoperative follow-up (24 hours after TAVR: (11.68±5.09) mmHg vs. (21.11±9.04) mmHg, P<0.001, 1 month after TAVR: (10.82±3.71) mmHg vs. (18.84±7.37) mmHg, P<0.001, 6 months after TAVR: (12.36±4.42) mmHg vs. (17.68±6.04) mmHg, P=0.003). There was no significant difference in NT-proBNP between BAV group and TAV group at each time point after operation (all P>0.05). There was no significant difference in paravalvular regurgitation and second prosthesis implantation between the two groups (all P>0.05). Conclusions: AS patients with BAV or TAV experience hemodynamic improvement and obvious left ventricular reverse remodeling after TAVR, and the therapeutic effects of TAVR are similar between BAV and TAV AS patients in the short-term post TAVR.

Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial☆.

BACKGROUND: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/µl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. RESULTS: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%). CONCLUSIONS: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.

[Different revascularization strategies for patients with coronary artery disease complicating reduced ejection fraction].

Objectives: To explore the short and long term outcomes of coronary artery disease(CAD) patients with heart failure with reduced ejection fraction (HFrEF) after two different revascularization strategies. Methods: The CAD patients with HFrEF who had undegone successful revascularization from January 1, 2005 to December 31, 2014 in Anzhen Hospital were analyzed based on registries. The baseline characteristics, changes of left heart function and the MACCE after a mean follow-up of 3.1 years were compared. Results: A total of 1 813 CAD patients with HFrEF who had undergone successful PCI (n=687) or CABG (n=1 126) satisfied the inclusion criteria were included. The age of all patients included was (59.6±10.0) years and male patients accounted for 83.1%. For the coronary angiographic features, the CABG group showed higher SYNTAX score (27.3±10.2 vs 31.1±10.4, P<0.01) and greater left ventricular end diastolic diameter (LVEDD) [(59.8±7.2) vs (57.9±7.7)mm, P<0.001]. The LVEF before revascularization was similar in PCI and CABG group [(35.8±5.1)% vs (35.9±4.6)%, P>0.05]. At three-month, one-year or three-year follow-up after revascularization, the improvement of LVEF was similar in the two groups (P>0.05). After multivariable adjustment, three-year outcomes revealed that the risks of all-cause mortality and cardiac death were not statistically significant between CABG and PCI group (16.3% vs 14.3%, HR=1.5, 95%CI: 1.2-2.1, P=0.07; 8.5% vs 8.2%, HR=1.3, 95%CI: 1.1-1.4, P=0.20). With regards to other endpoints, CABG group had a higher rate of stroke (6.2% vs 2.9%, HR=2.9, 95%CI:2.3-3.6, P<0.01) but a lower rate of repeat revascularization (6.5% vs 15.1%, HR=0.5, 95%CI:0.3-0.7, P<0.01) compared to PCI group. And for patients with SYNTAX score≥33, PCI group showed a comparable risk of all-cause mortality or cardiac death (HR=0.8, 95%CI: 0.4-1.3, P=0.06; HR=0.7, 95%CI:0.4-1.0, P=0.90). Conclusions: In CAD patients with HFrEF who had undergone successful revascularization, PCI is not inferior to CABG for long-term survival. PCI should be taken into consideration to become an alternative strategy in patients with left ventricular dysfunction.

[Interventional strategies and perioperative complications of chronic total coronary occlusion in combination with bifurcation lesions].

Objective: To analyze the clinical characteristics of chronic total coronary occlusion (CTO) combined with bifurcation lesions and the features of coronary intervention and perioperative complications. Methods: This study adopted retrospective cross-sectional research methods and included 673 patients who underwent interventional therapy for chronic total occlusion in Beijing Anzhen Hospital. According to whether there were side branches (diameter ≥2 mm) within 5 mm before and after the CTO occlusion segment, patients were divided into bifurcation group (337 cases) and non-bifurcation group (336 cases). The measurement data did not conform to the normal distribution and were represented as M (Q1, Q3). The clinical risk factors, coronary angiography characteristics, interventional treatment strategies and perioperative complications were compared between the two groups. Results: The patients in the bifurcation group were 60 (51, 65) years old, and 86.6% (292 cases) were male; the patients in the non-bifurcation group were 60 (52, 66) years old, and 83.0% (279 cases) were male.Coronary artery disease in all patients was mainly multivessel disease, of which three-vessel disease accounted for 59.9% (403 cases) and double-vessel disease accounted for 25.4% (171 cases).The target vessel in the bifurcation group was predominantly left anterior descending artery (62.3%, 210 cases), and the target vessel in the non-bifurcation group was more common in the right coronary artery (56%, 188 cases). The target vessel diameter was larger in the bifurcation group (2.91(2.71, 3.24) mm vs 2.80(2.55, 3.13) mm, P<0.001). Most patients used the antegrade technique (88%, 592 cases), and the use of antegrade technique in the bifurcation group (91.9%, 307 cases) was higher than that in the non-bifurcation group (84.8%, 285 cases) (P=0.012). After CTO-PCI, 72.8% (490 cases) of patients achieved successful angiography. A total of 73 patients (10.8%) had perioperative complications, and there was no statistical difference between the two groups. However, the incidence of perioperative myocardial infarction was higher in the bifurcation group (5.9%, 20 cases) than non-bifurcation group (2.7%, 9 cases) (P=0.038). Conclusions: CTO complicated with bifurcation lesions are very common in clinical practice. Most patients with CTO have multiple coronary artery disease at the same time. The target vessel is more common in the left anterior descending artery, and the diameter of the vessel is larger. It is more common to use antergrade technique, accompanied by more perioperative myocardial infarctions.

[Effects of cortical bone trajectory screw in adjacent-segment disease after posterior lumbar interbody fusion].

Objective: To investigate the effect of the cortical bone trajectory (CBT) screw fixation combined with midline lumbar fusion (MIDLF) for adjacent spondylopathy after posterior lumbar interbody fusion. Methods: A retrospective analysis was conducted in 16 patients, including 9 males and 7 females, with a mean age of (68±6) years, who underwent revision surgery for adjacent spondylopathy after posterior lumbar fusion surgery using CBT combined with MIDLF technology in Sir Run Run Shaw Hospital, Zhejiang University from May 2013 to August 2019. The reasons for revision were radiculalgia in 4 cases, intermittent claudication in 10 cases and protrusive dissociate in 2 cases. Eleven cases had 1 segment fused in the first operation, while the other 5 cases received fusion in 2 segments. The average interval time between the first operation and the revision operation was (7.5±2.0) years. For the levels underwent revision, 1 case was L2/3, 6 cases were L3/4, 7 cases were L4/5 and 2 cases were L5/S1. Before the operation, all the patients took X-rays scans of the thoracic and lumbar spine. CT and MRI scans were also performed. The operation time, intraoperative bleeding, surgical complications, visual analog scale (VAS) of low back and leg pain before the operation and at each follow-up were all recorded. Oswestry disability index (ODI) questionnaire was used to evaluate the functional improvement of patients after the operation. Results: All operations were completed successfully. The operation time was 120-240 (170±30) mins, intraoperative bleeding was 100-280 (220±45) ml. One case had a slight split in the isthmus, and the screw was inserted smoothly after adjusting the insertion point. In one case, the cerebrospinal fluid leaked during the operation and was successfully treated with conservative methods including no pillow supine treatment and strengthened anti-infection. The average follow-up time was of (19.5±1.3) months. The VAS of low back pain was 2.9±1.7 before the operation and it was 1.8±0.5 at the last follow-up, and the difference was statistically significant (P<0.01). The VAS of leg pain was 5.9±1.5 before the operation and it was 1.5±0.4 at the last the follow-up (P<0.01). The ODI score was 34.5±3.2 preoperatively and it decreased to 12.6±4.2 at the last follow-up, the difference was statistically significant (P<0.01). Conclusion: CBT technique combined with MIDLF for the adjacent-segment disease after posterior lumbar interbody fusion is minimally invasive and convenient, with good clinical effects. This technique can be used as an option for the revision of adjacent spondylopathy.