A Novel Method for the Rat Model of Abdominal Aortic Aneurysm Induced by Retroperitoneal Implantation of an Osmotic Pump System With Lipopolysaccharide.

BACKGROUND: Few methods can cocurrently mimic the pathological characteristics and nature history of human abdominal aortic aneurysms (AAAs), especially for the exist of the self-healing tendency of rodents. This study tested a novel method for the AAA rat model induced by retroperitoneal implantation of an osmotic pump system with lipopolysaccharide (LPS) based on the hypothesis that chronic inflammation of perivascular adipose tissue directly influenced the development and progression of AAAs. METHODS: 20 male Sprague-Dawley rats (10-month-old) fed with the Paigen diet were randomly divided into 4 groups: the blank group ×2, the sham group ×4, the empty capsule group ×4, and the LPS capsule group ×10. The LPS capsule group received implantations of the ALZET® osmotic pump capsule with LPS (3.6 µg/day) parallel to the abdominal aorta through a retroperitoneal approach. Two weeks later, 6 rats were randomly selected from the LPS capsule group to form the anti-inflammatory group and received implantations of another osmotic pump capsule with interleukin (IL)-10 (75 ng/day) through the same approach. The changes in abdominal aortic diameter were observed by ultrasound every 2 weeks, and samples were harvested for histopathologic and immunohistochemical analysis 6 weeks later. RESULTS: Within the 6 weeks after modeling, the LPS capsule group showed sustained and significant aortic dilatation (P < 0.01), while the anti-inflammatory group showed a rapid and obvious shrinkage 2 weeks after the IL-10 osmotic pump capsule implantation (P < 0.01). The LPS capsule group presented excellent pathological mimicking of human AAAs and showed severe medial degeneration with the least elastic content among the 5 groups at the end of the sixth week (P < 0.05). Notably, the anti-inflammatory group showed perfect medial preservation with the most elastic content (P < 0.05) and the highest elastin/collagen ratio (P < 0.01) at the end of the study. Matrix metalloproteinases (MMP) 2 and 9 and toll-like receptor 2 showed strong expression in the LPS capsule group at the end of the sixth week, which was significantly higher than that in the blank group and sham group. Interestingly, the anti-inflammatory group showed a slightly higher MMP9 expression than the LPS capsule group though there was no statistical difference between them. CONCLUSIONS: This novel method for the rat AAA model induced by retroperitoneal implantation of an osmotic pump capsule with LPS can concurrently mimic the histological characteristics and natural history of human AAAs. Further studies were needed to improve the osmotic pump system.

First-in-Human Clinical Trial of the WeFlow-JAAA Endograft System in Patients With Juxtarenal Abdominal Aortic Aneurysms.

OBJECTIVE: To preliminarily evaluate the safety and efficacy of the WeFlow-JAAA endograft, a novel off-the-shelf device designed for the repair of juxtarenal abdominal aortic aneurysms (JRAAAs) and pararenal abdominal aortic aneurysms (PRAAAs). METHODS: This prospective single-arm first-in-human clinical trial included patients with JRAAAs (infrarenal necks ≤10 mm) or PRAAAs with at least a 5 mm sealing zone below the superior mesenteric artery (SMA) who underwent endovascular repair using the WeFlow-JAAA endograft system. With this system, the celiac artery was addressed with a wide scallop, the renal arteries (RAs) were addressed with 2 standard inner branches, and the SMA was addressed with a "mini-inner-cuff" reinforced fenestration. The primary efficacy endpoint was the clinical success at 12 months. The primary safety endpoint was the freedom from major adverse events (MAEs) in the first 30 days after surgery. RESULTS: Fifteen patients (all men; mean age 68.5±6.0 years) were enrolled between October 2019 and August 2021. The median infrarenal neck length was 0 mm (IQR, 0-4 mm). Technical success was achieved in all patients. No MAEs occurred in the first 30 days. The mean fluoroscopy time was 73.1±27.8 minutes, and the mean volume of contrast media was 130.7±29.4 mL. Clinical success was maintained in all patients at 12 months. No aortic-related deaths, aneurysm rupture, type I or type III endoleak, or open surgery conversion occurred during the follow-up period. The secondary intervention was required only in 1 patient who developed an occluded right RA stent 14 months after the procedure. CONCLUSION: The WeFlow-JAAA endograft device appears to be safe and efficacious in selected patients with JRAAAs or PRAAAs with more than 5 mm sealing zone below SMA. Large-scale, multicenter, and prospective studies with long-term follow-ups are ongoing to validate our findings in China. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04745546 (URL: Guo's Visceral Arteries Reconstruction: The First in Man Study of WeFlow-JAAA Stent Graft System-Full-Text View-ClinicalTrials.gov). CLINICAL IMPACT: The first-in-human clinical trial of the WeFlow-JAAA endograft system demonstrates promising safety and efficacy in treating juxtarenal abdominal aortic aneurysms (JRAAAs) and partial pararenal abdominal aortic aneurysms (PRAAAs). This innovative off-the-shelf device offers a potential alternative to traditional endovascular aortic repair. The successful outcomes, including technical success in all patients, freedom from major adverse events, and maintenance of clinical success at 12 months, suggest a potential shift in clinical practice towards using the WeFlow-JAAA endograft system for selected patients. This study paves the way for larger-scale, multicenter, prospective studies to further validate its long-term safety and efficacy, offering clinicians a new option for managing complex abdominal aortic aneurysms.

Association Between Aneurysm Wall Inflammation Detected by Imaging Perivascular Fat and Secondary Intervention Risk for Abdominal Aortic Aneurysm Patients After Endovascular Repair.

OBJECTIVE: To investigate the association between the imaging biomarker (volumetric perivascular characterization index [VPCI]) which indicates the aortic wall inflammation by mapping the spatial changes of perivascular fat attenuation on computed tomography angiography (CTA) and the reintervention risk for abdominal aortic aneurysm (AAA) patients after endovascular aortic repair (EVAR). METHODS: This case-control study included AAA patients undergoing EVAR from a single center (n=260). Cases were AAA patients undergoing reintervention after EVAR and a 1:1 frequency-matched control group of AAA patients post-EVAR with a shrunken or ≥3-year stable sac and free of reintervention signs during the follow-up. The predictive variable (VPCI trajectory) was converted to binary variables according to the changing trend of VPCI with follow-up time. As a quasi-complete separation data pattern, least absolute shrinkage and selection operator (lasso) regression was used to screen and prove the VPCI trajectory as the best predictor, and the performance was evaluated by calculating the accuracy, sensitivity, and specificity. RESULTS: Between 2010 and 2021, 15 AAA patients after EVAR with type I/III endoleak, aneurysm rupture, or impending rupture were included. Compared with the 1:1 frequency-matched controls with a shrunken or ≥3-year stable sac and free of reintervention signs during the follow-up, VPCI trajectories of the case group were all upward trends, whereas the controls showed 86.7% downward trends (p<0.001). The best predictive model of lasso regressions included 4 variables, and VPCI trajectory was the most outstanding, followed by the proximal landing zone, the distal landing zone, and the infrarenal ß angle. The accuracy, sensitivity, and specificity of predicting the risk of reintervention were as follows, respectively: 93.3%, 100%, and 86.7%. CONCLUSIONS: The wall inflammation detected by imaging perivascular adipose tissue based on the CTAs was strongly associated with the reintervention risk for AAA patients after EVAR, which might hold major promise as a new imaging biomarker for the mechanism and treatment study of human AAAs before and after EVAR. CLINICAL IMPACT: The study introduces a novel imaging biomarker which indicates the aortic wall inflammation by mapping spatial changes of perivascular fat attenuation on CTA. This biomarker demonstrates a strong association with the reintervention risk in AAA patients after EVAR. Incorporation of VPCI into clinical practice has the potential to enhance the traditional surveillance methods (CT/CTAs) by providing clinicians with a non-invasive method to assess aortic wall inflammation and predict the risk of reintervention. Additionally, this study might offer a valuable tool for mechanism and treatment research in humans with AAAs both pre- and post-EVAR, ultimately improving patient outcomes and refining therapeutic strategies.

Diagnostic accuracy of updated risk assessment criteria and development of novel computational prediction models for patients with suspected choledocholithiasis.

BACKGROUND: There are risks of choledocholithiasis in symptomatic gallstones, and some surgeons have proposed the identification of choledocholithiasis before cholecystectomy. Our goal was to evaluate the diagnostic accuracy of the latest guidelines and create computational prediction models for the accurate prediction of choledocholithiasis. METHODS: We retrospectively reviewed symptomatic gallstone patients hospitalized with suspected choledocholithiasis. The diagnostic performance of 2019 and 2010 guidelines of the American Society for Gastrointestinal Endoscopy (ASGE) and 2019 guideline of the European Society of Gastrointestinal Endoscopy (ESGE) in different risks. Lastly, we developed novel prediction models based on the preoperative predictors. RESULTS: A total of 1199 patients were identified and 681 (56.8%) had concurrent choledocholithiasis and were included in the analysis. The specificity of the 2019 ASGE, 2010 ASGE, and 2019 ESGE high-risk criteria was 85.91%, 72.2%, and 88.42%, respectively, and their positive predictive values were 85.5%, 77.4%, and 87.3%, respectively. For Mid-risk patients who followed 2019 ASGE about 61.8% of them did not have CBD stones in our study. On the choice of surgical procedure, laparoscopic cholecystectomy + laparoscopic transcystic common bile duct exploration can be considered the optimal treatment choice for cholecysto-choledocholithiasis instead of Endoscopic Retrograde Cholangio-Pancreatography (ERCP). We build seven machine learning models and an AI diagnosis prediction model (ModelArts). The area under the receiver operating curve of the machine learning models was from 0.77 to 0.81. ModelArts AI model showed predictive accuracy of 0.97, recall of 0.97, precision of 0.971, and F1 score of 0.97, surpassing any other available methods. CONCLUSION: The 2019 ASGE guideline and 2019 ESGE guideline have demonstrated higher specificity and positive predictive value for high-risk criteria compared to the 2010 ASGE guideline. The excellent diagnostic performance of the new artificial intelligence prediction model may make it a better choice than traditional guidelines for managing patients with suspected choledocholithiasis in future.

Incidence and Prognostic Associations of Early Postoperative Stroke and Death Among Patients Undergoing Inner Branched Thoracic Endovascular Repair of Aortic Arch Pathologies: A Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of this systematic review was to assess the incidences and associations of early postoperative stroke and death among patients undergoing inner branched thoracic endovascular aortic repair (TEVAR) of arch pathologies. METHODS: Electronic bibliographic sources (PUBMED, EMBASE, and CENTRAL) were searched up to February 2022 using a combination of thesaurus and free-text terms to identify the studies using branched TEVAR to treat aortic arch disease. The systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. All observational studies investigating the prognosis of inner branched TEVAR in the treatment of aortic arch pathologies were included. Independent extraction of articles was performed by two authors using predefined data fields, including study quality indications. All pooled analyses were based on a random-effects or fixed model according to the heterogeneity. RESULTS: A total of 23 case series totaling 532 participants were included after screening. After optimized selection (largest sample size, most detailed data, lowest risk of bias) from the overlapping data, 12 studies with 289 participants were included in data synthesis. The pooled incidence of 30-day postoperative stroke was 10.6% (95% CI 7.0%-14.2%; p=.41, I2=3%). Pooled 30-day mortality was 4.9% (95% CI 2.0%-7.8%; p=.38, I2=7%). Combined early stroke/death was 15.7% (95% CI 11.2%-20.3%; p=.30, I2=15%). Subgroup analyses of 11 studies (without data missing) showed that a higher incidence of 30-day postoperative stroke was found in studies with aged participants (age≥71.3 years, p=.010), the higher percentage of COPD (≥30%, p= .011) and non-dissection-related pathologies (≥60.8%, p=.011). The higher 30-day postoperative mortality was found in studies with a high percentage of previous coronary artery disease (≥34.5%, p=.023). CONCLUSIONS: This review demonstrated that there were acceptable rates of 30-day postoperative stroke and death among patients undergoing inner branched TEVAR. It is strongly necessary to perform a rigorous risk assessment of aortic plaque embolism and coronary artery disease when the surgical plan of the inner branched TEVAR is determined. CLINICAL IMPACT: Treatment arch pathologies with inner branched TEVAR provides acceptable early stroke rate and mortality. Aortic pathology mainly influenced the early stroke rate, and early recognizing high-risk patients for aortic plaque embolism is of supreme importance for reducing the early stroke rate. In addition, the history of coronary artery disease was strongly associated with early mortality, and attention should be paid to the coronary artery assessment and perioperative management of these patients.

A prospective, multicenter, single-arm clinical trial cohort to evaluate the safety and effectiveness of a novel stent graft system (WeFlow-JAAA) for the treatment of juxtarenal abdominal aortic aneurysm: A study protocol.

Introduction: Juxtarenal abdominal aortic aneurysms (JRAAAs) are challenging to cure by traditional endovascular aortic repair (EVAR). Due to the inherent disadvantages of the customized fenestrated and/or branched aortic endografts (such as delayed cycles with a risk of aneurysm rupture, unavailable in emergency or confine operations), several off-the-shelf devices have been developed for the treatment of JRAAA. However, these devices being used in clinical trials have been proven to have a non-negligible risk of reintervention and inadequate anatomic applicability. We have developed a new off-the-shelf aortic endograft system (WeFlow-JAAA) with a mixed design of inner branches and modified fenestrations. The purpose of this cohort study is to assess the safety and effectiveness of the innovative aortic endograft system. Methods and analysis: This is a prospective, multicenter, single-armed clinical trial cohort study. The enrolment will take place in 29 centers in China, and 106 adult patients with JRAAA will be enrolled in total. Clinical information and CT angiography (CTA) images will be collected and recorded. Patients will be followed up for 5 years. The primary safety endpoint is the rate of no major adverse event within 30 days after index EVAR. The primary efficacy endpoint is the rate of immediate technical success and no JRAAA-related reintervention within 12 months after the procedure.

Mechanisms of abdominal aortic aneurysm progression: A review.

Abdominal aortic aneurysm (AAA) is a common disease associated with significant cardiovascular morbidity and mortality. Up to now, there is still controversy on the choice of treatment method of AAA. Even so, the mechanisms of AAA progression are poorly defined, making targeting new therapies problematic. Current evidence favors an interaction of the hemodynamic microenvironment with local and systemic immune responses. In this review, we aim to provide an update of mechanisms in AAA progression, involving hemodynamics, perivascular adipose tissue, adventitial fibroblasts, vasa vasorum remodeling, intraluminal thrombus, and distribution of macrophage subtypes.

A systematic review and meta-analysis of real-world studies evaluating the association between beta-blocker use and postoperative adverse events of carotid endarterectomy.

OBJECTIVE: The objective of this study was to estimate the association of beta-blocker use with postoperative adverse events of carotid endarterectomy (CEA) based on real-world data. METHODS: Electronic bibliographic sources (MEDLINE, EMBASE, and CENTRAL) were searched up to April 2021 using a combination of thesaurus and free-text terms to identify the studies about the effect of beta-blockers on outcomes of CEA. The systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. All observational studies and randomized controlled trials investigating the effect of preoperative beta-blockers on the outcomes of CEA were included. Independent extraction of articles by two authors using predefined data fields, including study quality indicators. All pooled analyses were based on a random-effects model. RESULTS: A total of seven observational studies (six case-control studies and one cohort study) were included. Of the three case-control studies that examined the association of beta-blockers with composite postoperative adverse events, two studies including three datasets that totaled 24,161 participants were included in the quantitative synthesis, and the overall results showed a statistically significant association between beta-blocker use and composite postoperative adverse events of CEA (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.15-1.59; P = .0003; I2 = 13%). Publication bias was not present in the meta-analysis (Egger test showed nonsignificant results: P = .453). Two of the included studies utilized indirect measures of cerebral ischemia: intraoperative electroencephalograph, intraoperative hemodynamic indicators; and found a significant association between beta-blockers and intraoperative cerebral ischemia. Another two studies were included for meta-analysis on the association between beta-blockers and 30-day strokes or death of CEA (OR, 1.61; 95% CI, 0.98-2.65; P = .06; I2 = 0%). Of all included studies, there was only one cohort study that reported the association of beta-blockers with postoperative myocardial infarction by χ2 analysis (OR, 1.96; 95% CI, 1.86-2.07). CONCLUSIONS: This systematic review suggested that there was an increased risk of postoperative adverse outcomes of CEA among beta-blocker users compared with nonusers in the real world.

Development and validation of a nomogram for predicting prostate cancer in patients with PSA ≤ 20 ng/mL at initial biopsy.

ABSTRACT: The aim of this study was to construct a nomogram for predicting prostate cancer (PCa) in patients with PSA ≤ 20 ng/mL at initial biopsy.The patients with PSA ≤ 20 ng/mL who underwent prostate biopsy were retrospectively included in this study. The nomogram was developed based on predictors for PCa, which were assessed by multivariable logistic regression analysis. The receiver operating characteristic curve, calibration plots and decision curve analysis (DCA) were used to evaluate the performance of the nomogram.This retrospective study included 691 patients, who were divided into training set (505 patients) and validation set (186 patients). The nomogram was developed based on the multivariable logistic regression model, including age, total PSA, free PSA, and prostate volume. It had a high area under the curve of 0.857, and was well verified in validation set. Calibration plots and DCA further validated its discrimination and potential clinical benefits. Applying the cut-off value of 15%, our nomogram would avoid 42.5% of unnecessary biopsies while miss only 4.4% of PCa patients.The nomogram provided high predictive accuracy for PCa in patients with PSA ≤ 20 ng/mL at initial biopsy, which could be used to avoid the unnecessary biopsies in clinical practice.

[Influence of Precipitation Change on Soil Respiration in Desert Grassland].

Global climate change has significantly changed precipitation patterns. Soil respiration (SR), as an important pathway through which CO2 is released from the soil carbon pool into the atmosphere, may affect the carbon cycle process of terrestrial ecosystems and have a feedback effect on global climate change in response to precipitation change. However, at present there is limited understanding of how SR is affected by precipitation change. Field precipitation control experiments were conducted (with -40%, -20%, natural, 20%, and 40% precipitation) on desert grassland in the west of the Loess Plateau, to investigate the influence of precipitation change on SR dynamics and its relationship with soil water content, soil temperature, aboveground biomass, soil organic carbon, microbial biomass carbon, carbon-nitrogen ratio, and other factors. The results show that the diurnal variations of SR under different precipitation treatments were consistent in unimodal and bimodal models over three years. SR showed an increasing trend with added precipitation, relative to the control, and significant differences were observed between the second year (wetter) and the third year (drier) of the precipitation-manipulation experiment, indicating that precipitation changes had a legacy effect on SR. At the same time, SR was lowest under the -40% treatment and highest under the 40% treatment during the wetter year. The negative response of SR to precipitation exclusion treatments was stronger than the positive response to precipitation addition treatments. SR in drier years was significantly higher under precipitation addition treatments than the control, and the positive response of SR to increased precipitation treatment was significantly stronger than that under decreased precipitation treatment. In addition, soil water content, aboveground biomass, soil organic carbon, and carbon-nitrogen ratio were the environmental factors that obviously affected SR and increased with additional precipitation. SR increased with increases in soil water content, aboveground biomass, soil organic carbon, and carbon-nitrogen ratio, but decreased with increases in microbial biomass carbon. Among these factors, soil water content had the highest interpretation rate for SR, indicating that soil water content was the main environmental factor controlling SR in desert grassland. In both wetter and drier years, the amplitude of plant biomass input was lower than the amplitude of SR output under precipitation change, indicating that precipitation change may be unfavorable to soil carbon sequestration, especially in drier years, when precipitation change has a stronger influence on carbon pool output. Therefore, precipitation changes on SR in desert grassland in various dry and wet years may have different influences on the carbon cycle process of ecosystems, thus providing a reference for regional carbon budget assessment.

[Effects of Precipitation Changes on Plant Community Diversity and Soil C:N:P Ecological Stoichiometric Characteristics in a Desert Steppe of China].

Studying the influence of precipitation patterns on plant community diversity, soil C:N:P ecological stoichiometric characteristics, and the relationships between key soil factors and plant community diversity is of great significance for the protection of plant community diversity in desert grasslands. This paper was studied in the desert steppe of the west of Loess Plateau using a three-year precipitation manipulation experiment (40% reduction in precipitation, 20% reduction in precipitation, natural precipitation, 20% increase in precipitation, and 40% increase in precipitation), explored the influence of changes in precipitation in dry and wet years on the diversity of plant community and soil C:N:P ecological stoichiometric characteristics. And we also explored the relationship between soil C:N:P ecological stoichiometric characteristics and the key soil factors and the diversity of plant community under changes in precipitation. The results showed that in a normal year and the drier year (2013 and 2015), Patrick richness and Shannon-Wiener diversity index were significantly low under the 20% reduction treatment compared with the control and 40% increase treatments, respectively. During the wetter year, Patrick richness and Shannon-Wiener diversity index were no different between any of the precipitation treatments. In the normal year and the drier year, the soil organic carbon (SOC), total nitrogen (TN), and total phosphorus (TP) contents and the carbon-nitrogen ratio (C:N), carbon-phosphorus ratio (C:P), and nitrogen-phosphorus ratio (N:P) all decreased with an increase in precipitation (the decrease in the C:N ratio was statistically significant). During the wetter year, SOC, TN, C:P, and N:P increased with an increase in precipitation. During the normal year, precipitation treatments had no significant influence on soil water content, having a limited influence on the plant community. TN, N:P, SOC, C:N, and microbial biomass nitrogen (MBN) had a more prominent influence on plant community diversity. In the wetter year, precipitation was abundant leading to a rise in soil nutrients. Water was not the most important factor limiting to plant growth whereas soil water content, soil nutrients, and ecological stoichiometric characteristics jointly regulate plant community diversity. In the drier years, precipitation treatments had a significant impact on soil water content, whereby an increase in precipitation led to high losses of soil nutrients. Therefore, soil water content was the most important factor affecting plant community diversity during drier years. These observations indicate that under dry and wet years, plant community diversity and soil C:N:P ecological stoichiometric characteristics have variable responses to precipitation and soil C:N:P effect on plant community were also different. These results provide a theoretical basis for the protection and management of desert steppe systems under future projected changes in precipitation.

A Pilot Study of 18F-DCFPyL PET/CT or PET/MRI and Ultrasound Fusion Targeted Prostate Biopsy for Intra-Prostatic PET-Positive Lesions.

OBJECTIVES: The purpose of this study was to evaluate the feasibility and diagnostic performance of prostate-specific membrane antigen (PSMA) based 18F-DCFPyL PET/CT-ultrasound (PET/CT-US) or PET/MRI-ultrasound (PET/MRI-US) fusion targeted biopsy for intra-prostatic PET-positive lesions. METHODS: From April 2018 to November 2019, we prospectively enrolled 55 candidates to perform PET/CT-US or PET/MRI-US fusion targeted biopsies for solitary PET-positive prostate lesions (two to four cores/lesion). The positive rates of prostate cancer based on patients and biopsy cores were calculated respectively. With reference to the pathological results of biopsy cores, the MR signal characteristics in the area of the PET-positive lesion were analyzed for the patients who underwent PET/MRI. RESULTS: A total of 178 biopsy cores were taken on the 55 patients. One hundred forty-six biopsy cores (82.0%, 146/178) from 51 (92.7%, 51/55) patients were positive for prostate cancer; 47 (85.5%, 47/55) were clinically significant prostate cancer. It is noteworthy that nine patients underwent both 18F-DCFPyL PET/CT and PET/MRI examinations; the seven patients with prostate cancer showed abnormal MR signal in the area of the PET-positive lesion while the other two patients with prostatic hyperplasia and prostatitis showed normal MR signal in the area of the PET-positive lesion. CONCLUSION: This study indicated that 18F-DCFPyL PET/CT-US or PET/MRI-US fusion targeted prostate biopsies may be valuable for prostate cancer diagnosis and have a high detection rate of clinically significant prostate cancer for PET-positive lesions. PET/MR can rule out some false PET-positive lesions, which may potentially reduce unnecessary prostate biopsies.

Is serum vitamin D deficiency before gestational 20 weeks a risk factor for preeclampsia?

OBJECTIVE: Our aim was to assess whether serum vitamin D deficiency before gestational 20 weeks was associated with an increased risk of preeclampsia. METHODS: We investigated the serum levels of 25(OH)D before gestational 20 weeks, and analyzed associations between the 25(OH)D and the risk of preeclampsia. 7976 pregnant women were enrolled in this study between January 2017 and July 2019 at the Obstetrics & Gynecology Hospital of Fudan University. Adjusted smoothing spline plots, subgroup analysis and multivariate logistic regression analysis was conducted to estimate the relative risk between 25(OH)D and preeclampsia. RESULTS: After fully adjusting the confounding factors, serum vitamin D is a protective factor in preeclampsia (OR = 0.85, P = 0.04). Compared with adequate vitamin D, vitamin D deficiency (OR = 1.55, P = 0.031), deficiency (OR = 1.50, P = 0.049) and severe deficiency (OR = 2.6, P = 0.005) are independent of preeclampsia in pregnant women Risk factors. CONCLUSION: Vitamin D deficiency before gestational 20 weeks is a risk factor for preeclampsia.

Outcomes of Anticoagulant Therapy with Low-Molecular-Weight Heparin (LMWH) and Warfarin for Thromboangiitis Obliterans (TAO).

BACKGROUND: Thromboangiitis obliterans (TAO) is a chronic, non-atherosclerotic, progressive inflammatory vascular disease affecting the small- and medium-size arteries and veins of the extremities. OBJECTIVE: To evaluate whether long-term anticoagulation with low-molecular-weight heparin (LMWH) and warfarin is beneficial for treating the inflammation and symptoms associated with TAO. METHODS: Patients with TAO who underwent anticoagulation as the mainstay of treatment were included in this prospective study. Rest pain relief and healing of trophic lesions (as the primary and secondary endpoint) were investigated at Day 14 and after 6 months of follow-up. High sensitivity C-reactive protein (hsCRP), monocyte count, and ankle-brachial index (ABI) were recorded, and the difference was compared before and after 2-week anticoagulation. The Chi-square test was used to compare the difference between anticoagulant and aspirin groups (based on the literature). RESULTS: From 2014 to 2019, 18 patients were included. Only 1 patient with wet gangrene received endo-therapy for a failing stent at the start of treatment. After ~14 days, 12 of 13 (92%) patients showed complete ulcer healing, and 17 of 18 (94%) patients showed complete relief from rest pain. Monocyte-counts and hsCRP levels decreased significantly (p<0.001) after a 2-week period of anticoagulation with LMWH. The mean follow-up was 2.6 years (range 0.5-5 years). At 6 months, all patients showed relief of rest pain and complete healing of trophic lesions. All endpoints were significantly improved compared with the aspirin group (p<0.01), and no rest pain or ulcer/gangrene recurred during follow-up. CONCLUSION: Anticoagulant therapy may alleviate the inflammation and symptoms of TAO.

Development and validation of a nomogram for the early prediction of preeclampsia in pregnant Chinese women.

To make early predictions of preeclampsia before diagnosis, we developed and validated a new nomogram for the early prediction of preeclampsia in pregnant Chinese women. A stepwise regression model was used for feature selection. Multivariable logistic regression analysis was used to develop the prediction model. We incorporated BMI, blood pressure, uterine artery ultrasound parameters, and serological indicator risk factors, and this was presented with a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed. The signature, which consisted of 11 selected features, was associated with preeclampsia status (P < 0.1) for the development dataset. Predictors contained in the individualized prediction nomogram included BMI, blood pressure, uterine artery ultrasound parameters, and serological indicator levels. The model showed good discrimination, with an area under the ROC curve of 0.8563 (95% CI: 0.8364-0.8761) and good calibration. The nomogram still had good discrimination and good calibration when applied to the validation dataset (area under ROC curve of 0.8324, 95% CI: 0.7873-0.8775). Decision curve analysis demonstrated that the nomogram was clinically useful. The nomogram presented in this study incorporates BMI, blood pressure, uterine artery ultrasound parameters, and serological indicators and can be conveniently used to facilitate the individualized prediction of preeclampsia.

Comparison of 18F-DCFPyL and 18F-FDG PET/computed tomography for the restaging of clear cell renal cell carcinoma: preliminary results of 15 patients.

OBJECTIVES: This study aimed to compare the diagnostic performance of F-DCFPyL and 2-deoxy-2-[F]fluoro-D-glucose (F-FDG PET/computed tomography in the restaging of clear cell renal cell carcinoma after nephrectomy. METHODS: In this retrospective study, a total of 15 patients with suspected local recurrence of clear cell renal cell carcinoma or metastasis after surgery underwent both F-DCFPyL and F-FDG PET/computed tomography. A systematic comparison of the maximum standardized uptake value and the target to background ratio was carried out between the lesions detected by the two tracers. RESULTS: A total of 42 lesions were detected either by F-DCFPyL PET/computed tomography or by F-FDG PET/computed tomography. F-DCFPyL PET/computed tomography, but not F-FDG PET/computed tomography, accurately distinguished the two local recurrence from four postoperative changes. The remaining 36 lesions were soft tissue (14) and bone lesions (22); all 36 lesions were detected by F-DCFPyL PET/computed tomography while only 10 (10/14) soft tissue lesions and 12 (12/22) bone lesions were detected by F-FDG PET/computed tomography. The higher detection rate of soft tissue lesions using F-DCFPyL PET/computed tomography was not statistically significant (P = 0.125); however, F-DCFPyL PET/computed tomography was statistically better (P = 0.002) at detecting bone lesions. The average maximum standardized uptake value and target to background ratio of F-DCFPyL were significantly higher than that of F-FDG for soft tissue lesions (maximum standardized uptake value P = 0.005; target to background ratio P = 0.028) and bone lesions (maximum standardized uptake value P = 0.001; target to background ratio P = 0.001). CONCLUSIONS: Our preliminary results indicated that F-DCFPyL PET/computed tomography is superior to F-FDG PET/computed tomography for the detection of local recurrence at both the surgical site and in bone metastasis while the tracers are comparable in the detection of soft tissue metastases.

Kidney ventrally rotation technique in retroperitoneal robot-assisted partial nephrectomy for posterior hilar tumor: technical feasibility and preliminary results.

PURPOSE: The retroperitoneal robotic assisted partial nephrectomy (RAPN) is suitable for tumors locating on the posterior side of the kidney. However, the posterior hilar tumor poses an additional surgical challenge due to the special location and poor tumor exposure. We developed a novel kidney ventrally rotation technique to overcome this difficulty during retroperitoneal RAPN and evaluated its efficacy in a retrospective case-control comparative study. METHODS: From March 2016 to April 2019, a total of 39 patients with posterior renal hilar tumor underwent retroperitoneal RAPN. The kidney ventrally rotation technique, which improved the tumor exposure by opening the peritoneum and rotating the kidney ventrally, was applied in 24 cases, and the conventional RAPN was performed in the other 15 cases (control group). Perioperative data was analyzed to evaluate the efficacy of the kidney ventrally rotation technique. RESULTS: In kidney rotation group, the 24 patients underwent RAPN successfully without converting to open surgery or radical nephrectomy. The warm ischemia time was 17.4 ± 6.6 min, which was significantly shorter than 24.5 ± 8.3 min in control group. The mean operation time (80 ± 24 min) and estimated blood loss (104 ± 65 ml) were not different from the control group. No sever complications occurred, and no positive surgical margin was found in all the malignant cases. After 14 months follow-up, no recurrence or metastasis occurred in all cases. CONCLUSION: Kidney ventrally rotation technique is safe and feasible for improving the exposure of posterior renal hilar tumor during retroperitoneal RAPN. It could be regarded as an efficient option for the management of posterior hilar tumor.

Laparoscopic nephron-sparing surgery for a tumor near the isthmus of a horseshoe kidney with a complicated blood supply.

A horseshoe kidney is a congenital kidney malformation commonly associated with complications such as hydronephrosis, renal calculi, and infections of the renal pelvis. Renal cell carcinoma is extremely rare in a horseshoe kidney; once it occurs, however, it is intractable because of vascular abnormalities. This is especially true in laparoscopic nephron-sparing surgery, even for tumors of <4 cm in diameter. We herein report a case involving an asymptomatic 65-year-old man with an incidental finding of a 4-cm solid mass near the isthmus of a horseshoe kidney on B-mode ultrasonography. Preoperative computed tomography of the renal artery revealed six arterial vessels supplying the affected kidney. Laparoscopic partial nephrectomy was performed. The outcome of this case suggests that laparoscopic nephron-sparing surgery might be a successful treatment method for a horseshoe kidney but that preoperative vessel evaluation and experienced laparoscopic skills are needed.

Encapsulated three-dimensional bioprinted structure seeded with urothelial cells: a new construction technique for tissue-engineered urinary tract patch.

BACKGROUND: Traditional tissue engineering methods to fabricate urinary tract patch have some drawbacks such as compromised cell viability and uneven cell distribution within scaffold. In this study, we combined three-dimensional (3D) bioprinting and tissue engineering method to form a tissue-engineered urinary tract patch, which could be employed for the application on Beagles urinary tract defect mode to verify its effectiveness on urinary tract reconstruction. METHODS: Human adipose-derived stem cells (hADSCs) were dropped into smooth muscle differentiation medium to generate induced microtissues (ID-MTs), flow cytometry was utilized to detect the positive percentage for CD44, CD105, CD45, and CD34 of hADSCs. Expression of vascular endothelial growth factor A (VEGFA) and tumor necrosis factor-stimulated gene-6 (TSG-6) in hADSCs and MTs were identified by Western blotting. Then the ID-MTs were employed for 3D bioprinting. The bioprinted structure was encapsulated by transplantation into the subcutaneous tissue of nude mice for 1 week. After retrieval of the encapsulated structure, hematoxylin and eosin and Masson's trichrome staining were performed to demonstrate the morphology and reveal collagen and smooth muscle fibers, integral optical density (IOD) and area of interest were calculated for further semi-quantitative analysis. Immunofluorescent double staining of CD31 and α-smooth muscle actin (α-SMA) were used to reveal vascularization of the encapsulated structure. Immunohistochemistry was performed to evaluate the expression of interleukin-2 (IL-2), α-SMA, and smoothelin of the MTs in the implanted structure. Afterward, the encapsulated structure was seeded with human urothelial cells. Immunofluorescent staining of cytokeratins AE1/AE3 was applied to inspect the morphology of seeded encapsulated structure. RESULTS: The semi-quantitative assay showed that the relative protein expression of VEGFA was 0.355 ±â€Š0.038 in the hADSCs vs. 0.649 ±â€Š0.150 in the MTs (t = 3.291, P = 0.030), while TSG-6 expression was 0.492 ±â€Š0.092 in the hADSCs vs. 1.256 ±â€Š0.401 in the MTs (t = 3.216, P = 0.032). The semi-quantitative analysis showed that the mean IOD of IL-2 in the MT group was 7.67 ±â€Š1.26, while 12.6 ±â€Š4.79 in the hADSCs group, but semi-quantitative analysis showed that there was no statistical significance in the difference between the two groups (t = 1.724, P = 0.16). The semi-quantitative analysis showed that IOD was 71.7 ±â€Š14.2 in non-induced MTs (NI-MTs) vs. 35.7 ±â€Š11.4 in ID-MTs for collagen fibers (t = 3.428, P = 0.027) and 12.8 ±â€Š1.9 in NI-MTs vs. 30.6 ±â€Š8.9 in ID-MTs for smooth muscle fibers (t = 3.369, P = 0.028); furthermore, the mean IOD was 0.0613 ±â€Š0.0172 in ID-MTs vs. 0.0017 ±â€Š0.0009 in NI-MTs for α-SMA (t = 5.994, P = 0.027), while 0.0355 ±â€Š0.0128 in ID-MTs vs. 0.0035 ±â€Š0.0022 in NI-MTs for smoothelin (t = 4.268, P = 0.013), which indicate that 3D bioprinted structure containing ID-MTs could mimic the smooth muscle layer of native urinary tract. After encapsulation of the urinary tract patch for additional cell adhesion, urothelial cells were seeded onto the encapsulated structures, and a monolayer urothelial cell was observed. CONCLUSION: Through 3D bioprinting and tissue engineering methods, we provided a promising way to fabricate tissue-engineered urinary tract patch for further investigation.

A Urine-Based Liquid Biopsy Method for Detection of Upper Tract Urinary Carcinoma.

BACKGROUND: Conventional clinical detection methods such as CT, urine cytology, and ureteroscopy display low sensitivity and/or are invasive in the diagnosis of upper tract urinary carcinoma (UTUC), a factor precluding their use. Previous studies on urine biopsy have not shown satisfactory sensitivity and specificity in the application of both gene mutation or gene methylation panels. Therefore, these unfavorable factors call for an urgent need for a sensitive and non-invasive method for the diagnosis of UTUC. METHODS: In this study, a total of 161 hematuria patients were enrolled with (n = 69) or without (n = 92) UTUC. High-throughput sequencing of 17 genes and methylation analysis for ONECUT2 CpG sites were combined as a liquid biopsy test panel. Further, a logistic regression prediction model that contained several significant features was used to evaluate the risk of UTUC in these patients. RESULTS: In total, 86 UTUC- and 64 UTUC+ case samples were enrolled for the analysis. A logistic regression analysis of significant features including age, the mutation status of TERT promoter, and ONECUT2 methylation level resulted in an optimal model with a sensitivity of 94.0%, a specificity of 93.1%, the positive predictive value of 92.2% and a negative predictive value of 94.7%. Notably, the area under the curve (AUC) was 0.957 in the training dataset while internal validation produced an AUC of 0.962. It is worth noting that during follow-up, a patient diagnosed with ureteral inflammation at the time of diagnosis exhibiting both positive mutation and methylation test results was diagnosed with ureteral carcinoma 17 months after his enrollment. CONCLUSION: This work utilized the epigenetic biomarker ONECUT2 for the first time in the detection of UTUC and discovered its superior performance. To improve its sensitivity, we combined the biomarker with high-throughput sequencing of 17 genes test. It was found that the selected logistic regression model diagnosed with ureteral cancer can evaluate upper tract urinary carcinoma risk of patients with hematuria and outperform other existing panels in providing clinical recommendations for the diagnosis of UTUC. Moreover, its high negative predictive value is conducive to rule to exclude patients without UTUC.