A longitudinal and cross-sectional study of placental circulation between normal and placental insufficiency pregnancies.

INTRODUCTION: To longitudinally and cross-sectionally study the differences in the uterine artery pulsatility index (UTPI), umbilical artery pulsatility index (UAPI) and placental vascularization indices (PVIs, derived from 3-dimensional power Doppler) between normal and placental insufficiency pregnancies throughout gestation. METHODS: UTPI, UAPI and PVI were measured 6 times at 4- to 5- week intervals from 11 to 13+6 weeks-36 weeks. Preeclampsia (PE) and fetal growth restriction (FGR) were defined as placental insufficiency. Comparisons of UTPI, UAPI and PVI between normal and insufficiency groups were performed by one-way repeated measures analysis of variance. RESULTS: A total of 125 women were included: monitored regularly from the first trimester to 36 weeks of gestation: 109 with normal pregnancies and 16 with placental insufficiency. Longitudinal study of the normal pregnancy group showed that UTPI and UAPI decreased significantly every 4 weeks, while PVIs increased significantly every 8 weeks until term. In the placental insufficiency group however, this decrease occurred slower at 8 weeks intervals and UTPI stabilized after 24 weeks. No significant difference was noted in PVIs throughout pregnancy. Cross-sectional study from different stages of gestation showed that UTPI was higher in the insufficiency group from 15 weeks onward and PVIs were lower after 32 weeks. DISCUSSION: Compared to high-risk pregnancies with normal outcome, UTPI and UAPI needed a longer time to reach a significant change in those with clinical confirmation of placental insufficiency pregnancies and no significant change was found in PVI throughout gestation. UTPI was the earliest factor in detecting adverse outcome pregnancies.

IL-36 Regulates Neutrophil Chemotaxis and Bone Loss at the Oral Barrier.

Tissue-specific mechanisms regulate neutrophil immunity at the oral barrier, which plays a key role in periodontitis. Although it has been proposed that fibroblasts emit a powerful neutrophil chemotactic signal, how this chemotactic signal is driven has not been clear. The objective of this study was to investigate the site-specific regulatory mechanisms by which fibroblasts drive powerful neutrophil chemotactic signals within the oral barrier, with particular emphasis on the role of the IL-36 family. The present study found that IL-36γ, agonist of IL-36R, could promote neutrophil chemotaxis via fibroblast. Single-cell RNA sequencing data disclosed that IL36G is primarily expressed in human and mouse gingival epithelial cells and mouse neutrophils. Notably, there was a substantial increase in IL-36γ levels during periodontitis. In vitro experiments demonstrated that IL-36γ specifically activates gingival fibroblasts, leading to chemotaxis of neutrophils. In vivo experiments revealed that IL-36Ra inhibited the infiltration of neutrophils and bone resorption, while IL-36γ promoted their progression in the ligature-induced periodontitis mouse model. In summary, these data elucidate the function of the site-enriched IL-36γ in regulating neutrophil immunity and bone resorption at the oral barrier. These findings provide new insights into the tissue-specific pathophysiology of periodontitis and offer a promising avenue for prevention and treatment through targeted intervention of the IL-36 family.

[Multi-phase CT synthesis-assisted segmentation of abdominal organs].

OBJECTIVE: To propose a method for abdominal multi-organ segmentation assisted by multi-phase CT synthesis. METHODS: Multi-phase CT synthesis for synthesizing high-quality CT images was used to increase the information details for image segmentation. A transformer block was introduced to help to capture long-range semantic information in cooperation with perceptual loss to minimize the differences between the real image and synthesized image. RESULTS: The model was trained using multi-phase CT dataset of 526 total cases from Nanfang Hospital. The mean maximum absolute error (MAE) of the synthesized non-contrast CT, venous phase contrast- enhanced CT (CECT), and delay phase CECT images from arterial phase CECT was 19.192±3.381, 20.140±2.676 and 22.538±2.874, respectively, which were better than those of images synthesized using other methods. Validation of the multi-phase CT synthesis-assisted abdominal multi-organ segmentation method showed an average dice coefficient of 0.847 for the internal validation set and 0.823 for the external validation set. CONCLUSION: The propose method is capable of synthesizing high-quality multi-phase CT images to effectively reduce the errors in registration between different phase CT images and improve the performance for segmentation of 13 abdominal organs.

Context-aware deep network for coronary artery stenosis classification in coronary CT angiography.

Automatic coronary artery stenosis grading plays an important role in the diagnosis of coronary artery disease. Due to the difficulty of learning the informative features from varying grades of stenosis, it is still a challenging task to identify coronary artery stenosis from coronary CT angiography (CCTA). In this paper, we propose a context-aware deep network (CADN) for coronary artery stenosis classification. The proposed method integrates 3D CNN with Transformer to improve the feature representation of coronary artery stenosis in CCTA. We evaluate the proposed method on a multicenter dataset (APOLLO study with NCT05509010). Experimental results show that our proposed method can achieve the accuracy of 0.84, 0.83, and 0.86 for stenosis diagnosis on the lesion, artery, and patient levels, respectively.

Nickel-Catalyzed Antibody Bioconjugation.

New biocompatible methods for post-translational protein modification are challenging to develop but crucial to create improved chemical probes and optimize next-generation biologic therapies such as antibody-drug conjugates (ADCs). Herein, we describe the bottom-up construction of an aqueous nickel-catalyzed cross-coupling for the chemospecific arylation of cysteine residues on peptides and proteins and its use for the preparation of ADCs. A variety of arene linkages are exemplified, enabling the incorporation of small molecules, probes, and cytotoxic payloads. The utility of this new bioconjugation platform in a drug discovery setting is highlighted by the construction of novel ADCs with target-mediated in vitro cytotoxic activity.

[Effect of equal temperature bladder irrigation in patients with transurethral resection of prostate: A meta-analysis].

OBJECTIVE: To evaluate the effect of equal temperature bladder irrigation on bladder spasm, postoperative bleeding, vital signs and discomfort of chills in patients of transurethral resection of prostate using meta-analysis. METHODS: Several electronic databases included Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, China Biology Medicine (CBM) were searched systematically for published randomized controlled trial about equal temperature bladder irrigation in patients with transurethral resection of prostate before November 20, 2019. Two reviewers selected independently the literature in the light of the inclusion and exclusion criteria, assessed the risk of bias by quality assessment and extracted data which were consisted of clinical efficacy indexes, such as incidence of bladder spasm, severity of bladder spasm, incidence of tube plugging, amount of bladder flushing fluid, time of bladder flushing, heart rate, systolic pressure, diastolic pressure, and incidence of chills. Data were pooled using fixed-effects model or random-effects model, and the summary effect measure was calculated by risk ratio (RR) or mean difference (MD) and 95% confidence interval (95%CI). Meta-analysis was performed by Review Manager 5.3 Software. RESULTS: In the study, 13 randomized controlled trails met the requirement with a total of 2 033 patients of transurethral resection of prostate were included, of whom 1 015 were carried out with equal temperature bladder irrigation and 1 018 with room temperature bladder irrigation. The results of meta-analysis showed that incidence of bladder spasm [RR=0.51, 95%CI (0.45, 0.57), P < 0.001], severity of bladder spasm [MD=-1.61, 95%CI (-2.00, -1.23), P < 0.001], incidence of urinary blockage [RR=0.29, 95%CI (0.19, 0.44), P < 0.001], dosage of bladder irrigation [MD=-6.75, 95%CI (-7.33, -6.17), P < 0.001], time of bladder rinse [MD=-7.60, 95%CI (-11.91, -3.29), P < 0.001], heart rate [MD=-13.68, 95%CI (-15.19, -12.17), P < 0.001], systolic pressure [MD=-29.26, 95%CI (-31.92, -26.59), P < 0.001], diastolic pressure [MD=-29.36, 95%CI (-31.75, -26.98), P < 0.001], incidence of chills and discomfort [MD=0.37, 95%CI (0.31, 0.44), P < 0.001] in equal temperature group of the patients with transurethral resection of prostate had significantly statistical difference compared with room temperature group. CONCLUSION: Based on current available evidence, equal temperature bladder irrigation reduced the incidence of bladder spasm and urinary blockage, relieved bladder spasm, reduced dosage and time of bladder irrigation, and hardly affected normal vital signs and increased the patient' s comfort.

Pneumonitis After Concurrent Chemoradiation and Immune Checkpoint Inhibition in Patients with Locally Advanced Non-small Cell Lung Cancer.

AIMS: Pneumonitis is a common and potentially deadly complication of combined chemoradiation and immune checkpoint inhibition (CRT-ICI) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). In this study we sought to identify the risk factors for pneumonitis with CRT-ICI therapy in LA-NSCLC cases and determine its impact on survival. MATERIALS AND METHODS: We conducted a retrospective chart review of 140 patients with LA-NSCLC who underwent curative-intent CRT-ICI with durvalumab between 2018 and 2021. Pneumonitis was diagnosed by a multidisciplinary team of clinical experts. We used multivariable cause-specific hazard models to identify risk factors associated with grade ≥2 pneumonitis. We constructed multivariable Cox proportional hazard models to investigate the impact of pneumonitis on all-cause mortality. RESULTS: The median age of the cohort was 67 years; most patients were current or former smokers (86%). The cumulative incidence of grade ≥2 pneumonitis was 23%. Among survivors, 25/28 patients had persistent parenchymal scarring. In multivariable analyses, the mean lung dose (hazard ratio 1.14 per Gy, 95% confidence interval 1.03-1.25) and interstitial lung disease (hazard ratio 3.8, 95% confidence interval 1.3-11.0) increased the risk for pneumonitis. In adjusted models, grade ≥2 pneumonitis (hazard ratio 2.5, 95% confidence interval 1.0-6.2, P = 0.049) and high-grade (≥3) pneumonitis (hazard ratio 8.3, 95% confidence interval 3.0-23.0, P < 0.001) were associated with higher all-cause mortality. CONCLUSIONS: Risk factors for pneumonitis in LA-NSCLC patients undergoing CRT-ICI include the mean radiation dose to the lung and pre-treatment interstitial lung disease. Although most cases are not fatal, pneumonitis in this setting is associated with markedly increased mortality.

[Expression changes of NaV channel subunits correlate with developmental maturation of electrophysiological characteristics of rat cerebellar Purkinje neurons].

OBJECTIVE: To investigate the variations in the expression of voltage-gated sodium (Nav) channel subunits during development of rat cerebellar Purkinje neurons and their correlation with maturation of electrophysiological characteristics of the neurons. METHODS: We observed the changes in the expression levels of NaV1.1, 1.2, 1.3 and 1.6 during the development of Purkinje neurons using immunohistochemistry in neonatal (5-7 days after birth), juvenile (12-14 days), adolescent (21-24 days), and adult (42-60 days) SD rats. Using whole-cell patch-clamp technique, we recorded the spontaneous electrical activity of the neurons in ex vivo brain slices of rats of different ages to analyze the changes of electrophysiological characteristics of these neurons during development. RESULTS: The expression of NaV subunits in rat cerebellar Purkinje neurons showed significant variations during development. NaV1.1 subunit was highly expressed throughout the developmental stages and increased progressively with age (P < 0.05). NaV1.2 expression was not detected in the neurons in any of the developmental stages (P > 0.05). The expression level of NaV1.3 decreased with development and became undetectable after adolescence (P < 0.05). NaV1.6 expression was not detected during infancy, but increased with further development (P < 0.05). NaV1.1 and NaV1.3 were mainly expressed in the early stages of development. With the maturation of the rats, NaV1.3 expression disappeared and NaV1.6 expression increased in the neurons. NaV1.1 and NaV1.6 were mainly expressed after adolescence. The total NaV protein level increased gradually with development (P < 0.05) and tended to stabilize after adolescence. The spontaneous frequency and excitability of the Purkinje neurons increased gradually with development and reached the mature levels in adolescence. The developmental expression of NaV subunits was positively correlated with discharge frequency (r=0.9942, P < 0.05) and negatively correlated with the excitatory threshold of the neurons (r=0.9891, P < 0.05). CONCLUSION: The changes in the expression levels of NaV subunits are correlated with the maturation of high frequency electrophysiological properties of the neurons, suggesting thatmature NaV subunit expressions is the basis of maturation of electrophysiological characteristics of the neurons.

[Assessment of the diagnostic value and prognosis of different detection markers in endocervical adenocarcinoma].

Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.

[Study of risk factors of postherpetic neuralgia].

Objective: To analyze the clinical features and risk factors of herpes zoster and the risk factors of postherpetic neuralgia (PHN). Methods: A total of 2 840 patients diagnosed with herpes zoster in Peking University People's Hospital from January 2021 to April 2022 were included. The patients with herpes zoster were aged (59±16), and of which 1 314 (46.3%) patients were male. The patients were divided into PHN group and non-PHN group according to whether the patients with herpes zoster developed PHN. And there were 442 (15.6%) patients developed PHN aged (68±12), and of which 189 (42.8%) were male. The information and medical history of PHN group and non-PHN group were collected. The information of the use of glucocorticoids, immunosuppressive agents, biological agents and targeted medicine within 2 months before herpes zoster occurred, history of surgery within 6 months before herpes zoster occurred, and the duration of PHN were collected. Logistic regression analysis was used to analyze the risk factors of PHN. Results: Out of 2 840 patients, 2 056 (72.4%) with herpes zoster aged 50 years and above. Intercostal nerves was mostly involved in patients with herpes zoster, with a total of 1 532(53.9%). Hypertension (465 cases, 16.4%) accounted for the highest number of patients with chronic diseases, followed by diabetes (337 cases, 11.9%) and coronary heart disease (283 cases, 10.0%). Rheumatoid arthritis (41 cases, 1.4%) accounted for the highest number of patients with connective tissue diseases, followed by Sjogren's syndrome (31 cases, 1.1%), systemic lupus erythematosus (28 cases, 1.0%). Logistic regression analysis showed that age≥50 years old (OR: 4.581; 95%CI: 3.131-6.705),lesion on the upper limb and shoulder (OR: 1.858; 95%CI: 1.129-3.059), hypertension (OR: 1.963; 95%CI: 1.513-2.546) and immunosuppressive treatments (OR: 2.170; 95%CI: 1.254-3.753) were independent risk factors for PHN (all P<0.05). Conclusions: Herpes zoster mostly occurs in people aged 50 and above, and mainly affected intercostal nerves. The most common complications are hypertension and rheumatoid arthritis. Age≥50, lesion on upper limbs and shoulders, hypertension, and immunosuppressive treatments may be independent risk factors of PHN.

[Effect of autologous hematopoietic stem cell transplantation on minimal residual disease in patients with multiple myeloma].

Objective: To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on minimal residual disease (MRD) in patients with multiple myeloma (MM). Method: From August 2018 to August 2021, 92 patients newly diagnosed with MM who had received either the bortezomib combined with cyclophosphamide and dexamethasone (VCD) or the bortezomib, lenalidomide and dexamethasone (VRD) induction regimens followed by sequential ASCT were assessed for overall survival (OS) and the MRD negative rate. The differences in efficacy at 100 days after transplantation were assessed according to factors, including age, risk stratification, target organ damage, and pre-transplant regimen, etc. Results: Among the 92 patients, there were 45 males and 47 females, with a median age of 57.3 (35-67) years. Fifty-seven patients received the VCD regimen, and 35 received VRD as induction regimen. Forty-three patients received busulphan combined with cyclophosphamide and etoposide (BCV), and 49 patients received high-dose melphan (HDM) regimen as pre-transplantation treatment. After transplantation, the total complete remission (CR) rate of 92 patients increased from 23.9% (22/92) to 58.7% (54/92), and the MRD negative rate increased from 4.4% (4/92) to 33.7% (31/92), and the differences were statistically significant (all P<0.05). After transplantation, the MRD negative rates of patients with PR, VGPR and ≥CR before transplantation were 17.6% (6/34), 33.3% (12/36) and 59.1% (13/22), respectively (P=0.006). The CR rates of patients with or without plasmacytoma at initial diagnosis were 36.4% (4/11) and 65.4% (53/81), respectively (P=0.029), and the MRD negative rates were 18.2% (2/11) and 39.5% (32/81), respectively (P=0.037), and the differences were statistically significant. The MRD negative rates in high-risk patients and standard-risk group were 30.5% (12/28) and 42.9% (18/59), respectively (P=0.258). For patients who achieved efficacy above VGPR before transplantation, the MRD negative rates after transplantation in VCD-induced group and VRD group were 29% (9/31) and 59.3% (16/27), respectively (P=0.033), and in BCV group and HDM group were 24% (6/25) and 57.6% (19/33), respectively (P=0.016), the differences between the groups were both statistically significant. Conclusion: ASCT can overcome the adverse factors such as high-risk cytogenetic abnormalities, and significantly improve the CR rate and MRD negative rate of MM patients. However, the benefit for patients with plasmacytoma at initial diagnosis is not as good as that of patients without.

[Analysis of the diagnosis and treatment of patients with SMARCB1 (INI-1)-deficient sinonasal carcinoma].

Objective: To summarize the clinical features, treatments and outcomes of patients with SMARCB1(INI-1)-deficient sinonasal carcinoma (SDSC). Methods: Fifteen patients who were diagnosed as SDSC in Beijing Tongren Hospital from October 2016 to June 2021 were retrieved, including nine males and six females, ranged from 25 to 78 years old. For TNM stage, one case was in stage T2, one case was in stage T3, 13 cases were in stage T4; 13 cases were in stage N0, two cases were in stage N2; 14 cases were in stage M0, one case was in stage M1. The most common paranasal sinus affected by tumor was the ethmoid sinus. Five patients were treated by radical surgical resection combined with postoperative adjuvant therapy, four patients treated by neoadjuvant therapy with surgical resection, three patients treated by surgical resection only, one patient treated by neoadjuvant therapy with concurrent chemoradiotherapy, one patient treated by preoperative radiotherapy with surgery, and one patient received palliative chemotherapy. Immunohistochemical analysis was performed in all cases. The Kaplan-Meier method was used to draw the survival curve, and the Log-rank test was used to compare the difference to 20 undifferentiated carcinoma patients with positive INI-1 expression in the same period. Results: Immunohistochemical analysis showed the complete absence of INI-1 expression in the tumor nuclei in all 15 cases. The follow-up information was available with a median follow-up time of 21 months (3-56 months). The 3-year overall survival rate, disease specific survival rate, disease-free survival rate and metastasis-free survival rate were 58.9%, 58.9%, 36.4% and 31.2%, respectively. Disease-free survival in SDSC patients was significantly lower compared with undifferentiated carcinoma patients with positive INI-1 expression (HR=2.87,95%CI:0.92~8.91,P=0.043). Cox regression analysis showed that patients with comprehensive treatment based on surgery had a better prognosis than others (HR=8.61,95%CI:1.38~53.73,P=0.021). Conclusion: SDSC is a highly aggressive malignant tumor with the characteristics of easy recurrence, early metastasis and poor prognosis. INI-1 immunohistochemical analysis is recommended in the pathologically poorly differentiated sinonasal carcinoma. Comprehensive treatment based on radical resection may be the first choice for SDSC patients.

[Personalized therapy for Helicobacter pylori on initial treatment: the initial treatment is the decisive battle].

As widespread eradication treatment continues, the rate of (Helicobacter pylori, H. pylori) antibiotic resistance is increasing. Together with host CYP2C19 gene polymorphisms, H. pylori coccoid transformation, patient compliance, irregular treatment regimens or empirical repeated eradication therapy by physician, H. pylori eradication rates have gradually decreased. Personalized treatment is an effective measure to achieve successful eradication of H. pylori in the initial treatment. With the first approval of molecular diagnostic kit for H. pylori clarithromycin resistance in China and the updated definition of refractory H. pylori infection by the American Gastroenterological Association (AGA), the personalized treatment of H. pylori guided by antibiotic resistance genotype detection in initial treatment, that follows the latest international consensus and guidelines, conforms to the national situation and surpasses the international standards, has come to the forefront.

Impact of angiogenic inhibition in the treatment of newly diagnosed and recurrent glioblastoma: a meta-analysis based on randomized controlled trials.

OBJECTIVE: Glioblastoma (GBM) is the most common and aggressive primary malignant tumor of the central nervous system in adults with high recurrence and mortality rates. Although radiotherapy and temozolomide have become the standard therapeutic regimen for GBM as adjuvant chemoradiotherapy after surgical resection, clinical outcomes remain suboptimal. In recent years, targeted antiangiogenic therapy has attracted considerable attention, but its therapeutic efficacy and safety are still controversial. MATERIALS AND METHODS: Randomized controlled trials (RCTs) of chemoradiotherapy with or without bevacizumab for the treatment of glioblastoma were collected by searching on the Pubmed, Embase, Cochrane, Ovid, Scopus, Web of Science, and Google Scholar databases from the date of database establishment to February 2022. Meta-analysis was performed using RevMan 5.3 software after two investigators independently screened the literature, extracted data, and assessed the risk bias of included studies. RESULTS: A total of 7 RCTs were included. The meta-analysis showed that bevacizumab in combination with chemoradiotherapy was superior to chemoradiotherapy alone in terms of progression-free survival (PFS), with a statistically significant difference. Interestingly, bevacizumab in combination with chemoradiotherapy improved PFS more significantly in recurrent glioblastoma than in newly diagnosed glioblastoma. However, for overall survival (OS), the combination of bevacizumab with chemoradiotherapy was similar to chemoradiotherapy alone, which was not significantly different. With regard to safety, the incidence of most adverse events was higher in the combination of bevacizumab and chemoradiotherapy than in chemoradiotherapy alone, especially in terms of hematologic adverse events. CONCLUSIONS: Current evidence suggests that angiogenesis inhibitor-containing chemoradiotherapy regimens are preferentially recommended for patients with recurrent glioblastoma to prolong their progression-free survival, provided that safety is acceptable, but this does not confer a significant benefit on overall patient survival.

The value of placental vascularization indices for predicting preeclampsia and fetal growth restriction in different stages of gestation: A prospective and longitudinal study.

INTRODUCTION: To assess value of placental vascularization indices (PVIs) for predicting preeclampsia (PE) and fetal growth restriction (FGR) in different stages of pregnancy in high-risk women. METHOD: PVIs derived from 3-dimensional power doppler(3DPD) imaging were measured at seven stages of pregnancy: 11-13+6w, 15-19+6w, 20-23+6w, 24-27+6w, 28-31+6w, 32-36+6w, and ≥37w. PE and FGR were used as outcomes in logistic regression models. Area under the receiver operating characteristic (ROC) curve (AUC) of each PVI was calculated, cut-off points were determined to calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Finally, AUCs combined with baseline characteristics, uterine artery pulsatility index (UTPI) and PVIs were used to determine whether PVIs could increase the predictive value. RESULTS: Adverse outcomes occurred in 10.9% of pregnancies. Statistical differences appeared in 32-36+6w only. AUCs of vascularization index (VI) and vascularization flow index (VFI) for 32-36+6w were 0.79 (0.70-0.87, p: 0.000), and 0.78 (0.69-0.88, p: 0.000). Sensitivity, specificity, PPV, NPV, PLR, and NLR for VI were 0.91, 0.63, 20%, 98%, 2.39, and 0.15, and those for VFI were 0.62, 0.84, 29%, 95%, 3.75, and 0.45. AUC increased from 0.79 to 0.85 by adding PVIs to baseline characteristics and UTPI model. No statistical significance was found before 32w. DISCUSSION: VI and VFI were valuable for predicting PE and FGR at the 32-36+6w stage, while their values before 32w were poor.