Randomized Double-Blind Study of the Effect of Injectate Temperature on Intrathecal Bupivacaine Dose Requirement in Spinal Anesthesia for Cesarean Delivery.

BACKGROUND: Increasing the temperature of intrathecal local anesthetics has been shown to increase the speed of onset and block height of spinal anesthesia. However, how this influences dose requirement has not been fully quantified. The aim of this study was to determine and compare the effective dose for anesthesia for cesarean delivery in 50% of patients (ED50) of intrathecal bupivacaine given at temperatures of 37 °C (body temperature) or 24 °C (room temperature). METHODS: Eighty healthy parturients having elective cesarean delivery under combined spinal-epidural anesthesia were randomly assigned to receive intrathecal hyperbaric bupivacaine stored at 37 °C (body temperature group) or 24 °C (room temperature group). The first subject in each group received a bupivacaine dose of 10 mg. The dose for each subsequent subject in each group was varied with an increment or decrement of 1 mg based on the response (effective or noneffective) of the previous subject. Patients for whom the dose was noneffective received epidural supplementation after data collection with lidocaine 2% as required until anesthesia was sufficient for surgery. Values for ED50 were calculated using modified up-down sequential analysis with probit analysis applied as a backup sensitivity analysis. These values were compared and the relative mean potency was calculated. RESULTS: The ED50 (mean [95% confidence interval, CI]) of intrathecal hyperbaric bupivacaine was lower in the body temperature group (6.7 [5.7-7.6] mg) compared with the room temperature group (8.1 [7.7-8.6] mg) (P < .05). The relative potency ratio for intrathecal bupivacaine for the room temperature group versus the body temperature group was 0.84 (95% CI, 0.77-0.93). CONCLUSIONS: Warming hyperbaric bupivacaine to body temperature reduced the dose requirement for spinal anesthesia for cesarean delivery by approximately 16% (95% CI, 7%-23%).

Long-term survivors after curative-intent resection for intrahepatic cholangiocarcinoma.

OBJECTIVES: The objective of the current study was to characterize prognostic factors related to long-term recurrence-free survival after curative-intent resection of intrahepatic cholangiocarcinoma (ICC). METHODS: Data on patients who underwent curative-intent resection for ICC between 2000 and 2020 were collected from an international multi-institutional database. Prognostic factors were investigated among patients who recurred within 5 years versus long-term survivors who survived more than 5 years with no recurrence. RESULTS: Among 635 patients who underwent curative-intent resection for ICC, 104 (16.4%) patients were long-term survivors with no recurrence beyond 5 years after surgery. Patients who survived for more than 5 years with no recurrence were more likely to have less aggressive tumor features, as well as have undergone an R0 resection versus patients who recurred within 5 years after resection. On multivariable analysis, tumor size (>5 cm) (HR: 1.535, 95% CI: 1.254-1.879), satellite lesions (HR: 1.253, 95% CI: 1.003-1.564), and lymph node metastasis (HR: 1.733, 95% CI: 1.349-2.227) were independently associated with recurrence within 5 years. Patients who recurred beyond 5 years (n = 23), 2-5 years (n = 60), and within 2 years (n = 471) had an incrementally worse post-recurrence survival (PRS, 28.0 vs. 20.0 vs. 12.0 months, p = 0.032). Among patients with N0 status, tumor size (>5 cm) (HR: 1.612, 95% CI: 1.087-2.390) and perineural invasion (PNI) (HR: 1.562,95% CI: 1.081-2.255) were risk factors associated with recurrence. Among patients with N1 disease, only a minority (5/128, 3.9%) of patients survived with no recurrence to 5 years. CONCLUSION: Roughly 1 in 6 patients survived for more than 5 years with no recurrence following curative-intent resection of ICC. Among N0 patients, tumor recurrence was associated with tumor size and PNI. Only a small subset of N1 patients experienced long-term survival.

Laparoscopic-assisted full-sized liver transplantation with magnetically fast portal vein anastomosis: An initial cohort study.

BACKGROUND: Some cases of laparoscopic-assisted liver transplantation (LA-LT) with utilization of reduced-size grafts has been reported. We here introduced successful utilization of LA-LT with whole liver grafts and magnetic portal vein anastomosis. METHODS: Eight patients with liver cirrhosis were included for LA-LT using donor organs after cardiac death. The surgical procedures included purely laparoscopic explant hepatectomy and whole-liver graft implantation via the midline incision. After explant removal, the whole-liver graft was then placed in situ, and a side-to-side cavo-caval anastomosis with 4-5 cm oval opening was performed. The magnetic rings were everted on the donor and recipient portal vein, respectively, and the instant attachment of the two magnets at the donor and recipient portal vein allowed fast blood reperfusion, followed by continuous suturing on the surface of the magnets. RESULTS: The median operation time was 495 (range 420-630). The median time of explant hepatectomy and IVC anastomosis was 239 (range 150-300) min and 14.5 (range 10-19) min, respectively. Of note, the median anhepatic time was 25 (range 20-35) min. All the patients were discharged home with no major complications after more than six months follow-up. CONCLUSION: LA-LT with full-size graft is feasible and utilization of magnetic anastomosis would further simplify the procedure.

Preoperative anemia: impact on short- and long-term outcomes following curative-intent resection of gastroenteropancreatic neuroendocrine tumors.

BACKGROUND: The effect of preoperative anemia on clinical outcomes of patients undergoing resection of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has not been previously investigated. This study aimed to characterize how preoperative anemia affected short- and long-term outcomes of patients undergoing curative-intent resection of GEP-NETs. METHODS: Patients who underwent curative-intent resection for GEP-NETs between January 1990 and December 2020 were identified from 8 major institutions. The last preoperative hemoglobin level was recorded; anemia was defined as <13.5 g/dL in males or <12.0 g/dL in females based on the guides of the American Society of Hematology. The effect of anemia on postoperative outcomes was assessed on uni- and multivariate analyses. RESULTS: Among 1559 patients, the median age was 58 years (IQR, 48-66), and roughly one-half of the cohort was male (796 [51.1%]). Most patients had a pancreatic tumor (1040 [66.7%]), followed by small bowel (259 [16.6%]), duodenum (103 [6.6%]), stomach (66 [4.2%]), appendix (53 [3.4%]), and other locations (38 [2.6%]). The median preoperative hemoglobin level was 13.4 g/dL (IQR, 12.2-14.5). Overall, 101 (6.7%) and 119 (8.5%) patients received an intra- or postoperative packed red blood cell (pRBC) transfusion, respectively. A total of 972 patients (44.5%) experienced a postoperative complication. Although the overall incidence of complications was no different among patients who did (anemic: 48.7%) vs patients who did not (nonanemic: 47.3%) have anemia (P = .597), patients with preoperative anemia were more likely to develop a major (Clavien-Dindo grade ≥IIIa: 48.9% [anemic] vs 38.0% [nonanemic]; P = .006) and multiple (≥3 types of complications: 32.2% [anemic] vs 19.7% [anemic]; P < .001) complications. Of note, 1-, 3-, and 5-year overall survival (OS) rates were 96.7%, 90.5%, and 86.6%, respectively. On multivariable analysis, anemia (hazard ratio, 2.0; 95% CI, 1.2-3.2; P = .006) remained associated with worse OS; postoperative pRBC transfusion was associated with an OS (5-year OS: 75.0% vs 87.7%; P = .017) and recurrence-free survival (RFS; 5-year RFS: 66.9% vs 76.5%; P = .047). CONCLUSION: Preoperative anemia was commonly identified in roughly 1 in 3 patients who underwent curative-intent resection for GEP-NETs. Preoperative anemia was strongly associated with a higher risk of postoperative morbidity and worse long-term outcomes.

Early Onset Intrahepatic Cholangiocarcinoma: Clinical Characteristics, Oncological Outcomes, and Genomic/Transcriptomic Features.

INTRODUCTION: Data on clinical characteristics and disease-specific prognosis among patients with early onset intrahepatic cholangiocarcinoma (ICC) are currently limited. METHODS: Patients undergoing hepatectomy for ICC between 2000 and 2020 were identified by using a multi-institutional database. The association of early (≤50 years) versus typical onset (>50 years) ICC with recurrence-free (RFS) and disease-specific survival (DSS) was assessed in the multi-institutional database and validated in an external cohort. The genomic and transcriptomic profiles of early versus late onset ICC were analyzed by using the Total Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center databases. RESULTS: Among 971 patients undergoing resection for ICC, 22.7% (n = 220) had early-onset ICC. Patients with early-onset ICC had worse 5-year RFS (24.1% vs. 29.7%, p < 0.05) and DSS (36.5% vs. 48.9%, p = 0.03) compared with patients with typical onset ICC despite having earlier T-stage tumors and lower rates of microvascular invasion. In the validation cohort, patients with early-onset ICC had worse 5-year RFS (7.4% vs. 20.5%, p = 0.002) compared with individuals with typical onset ICC. Using the TCGA cohort, 652 and 266 genes were found to be upregulated (including ATP8A2) and downregulated (including UTY and KDM5D) in early versus typical onset ICC, respectively. Genes frequently implicated as oncogenic drivers, including CDKN2A, IDH1, BRAF, and FGFR2 were infrequently mutated in the early-onset ICC patients. CONCLUSIONS: Early-onset ICC has distinct clinical and genomic/transcriptomic features. Morphologic and clinicopathologic characteristics were unable to fully explain differences in outcomes among early versus typical onset ICC patients. The current study offers a preliminary landscape of the molecular features of early-onset ICC.

Perioperative Changes in Serum Transaminase Levels: Impact on Postoperative Morbidity Following Liver Resection of Hepatocellular Carcinoma.

OBJECTIVES: To define how dynamic changes in pre- versus post-operative serum aspartate aminotransferase (AST) and alanine aminotransaminase (ALT) levels may impact postoperative morbidity after curative-intent resection of hepatocellular carcinoma (HCC). BACKGROUND: Hepatic ischemia/reperfusion can occur at the time of liver resection and may be associated with adverse outcomes following liver resection. METHODS: Patients who underwent curative resection for HCC between 2010-2020 were identified from an international multi-institutional database. Changes in AST and ALT (CAA) on postoperative day (POD) 3 versus preoperative values () were calculated using the formula: based on a fusion index via Euclidean norm, which was examined relative to the comprehensive complication index (CCI). The impact of CAA on CCI was assessed by the restricted cubic spline regression and Random Forest analyses. RESULTS: A total of 759 patients were included in the analytic cohort. Median CAA was 1.7 (range, 0.9 to 3.25); 431 (56.8%) patients had a CAA<2, 215 (28.3%) patients with CAA 2-5, and 113 (14.9%) patients had CAA ≥5. The incidence of post-operative complications was 65.0% (n=493) with a median CCI of 20.9 (IQR, 20.9-33.5). Spline regression analysis demonstrated a non-linear incremental association between CAA and CCI. The optimal cutoff value of CAA=5 was identified by the recursive partitioning technique. After adjusting for other competing risk factors, CAA≥5 remained strongly associated with risk of post-operative complications (Ref. CAA<5, OR 1.63, 95%CI 1.05-2.55, P=0.03). In fact, the use of CAA to predict post-operative complications was very good in both the derivative (AUC 0.88) and external (ACU 0.86) cohorts (n=1137). CONCLUSIONS: CAA was an independent predictor of CCI after liver resection for HCC. Use of routine labs such as AST and ALT can help identify patients at highest risk of post-operative complications following HCC resection.

Classification of Intrahepatic Cholangiocarcinoma into Perihilar Versus Peripheral Subtype.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) constitutes a group of heterogeneous malignancies within the liver. We sought to subtype ICC based on anatomical origin of tumors, as well as propose modifications of the current classification system. METHODS: Patients undergoing curative-intent resection for ICC, hilar cholangiocarcinoma (CCA), or hepatocellular carcinoma (HCC) were identified from three international multi-institutional consortia of databases. Clinicopathological characteristics and survival outcomes were assessed. RESULTS: Among 1264 patients with ICC, 1066 (84.3%) were classified as ICC-peripheral subtype, whereas 198 (15.7%) were categorized as ICC-perihilar subtype. Compared with ICC-peripheral subtype, ICC-perihilar subtype was more often associated with aggressive tumor characteristics, including a higher incidence of nodal metastasis, macro- and microvascular invasion, perineural invasion, as well as worse overall survival (OS) (median: ICC-perihilar 19.8 vs. ICC-peripheral 37.1 months; p < 0.001) and disease-free survival (DFS) (median: ICC-perihilar 12.8 vs. ICC-peripheral 15.2 months; p = 0.019). ICC-perihilar subtype and hilar CCA had comparable OS (19.8 vs. 21.4 months; p = 0.581) and DFS (12.8 vs. 16.8 months; p = 0.140). ICC-peripheral subtype tumors were associated with more advanced tumor features, as well as worse survival outcomes versus HCC (OS, median: ICC-peripheral 37.1 vs. HCC 74.3 months; p < 0.001; DFS, median: ICC-peripheral 15.2 vs. HCC 45.5 months; p < 0.001). CONCLUSIONS: ICC should be classified as ICC-perihilar and ICC-peripheral subtype based on distinct clinicopathological features and survival outcomes. ICC-perihilar subtype behaved more like carcinoma of the bile duct (i.e., hilar CCA), whereas ICC-peripheral subtype had features and a prognosis more akin to a primary liver malignancy.

Low Prognostic Nutritional Index Is Common and Associated with Poor Outcomes following Curative-Intent Resection for Gastro-Entero-Pancreatic Neuroendocrine Tumors.

INTRODUCTION: To investigate the impact of prognostic nutritional index (PNI) on short- and long-term outcomes of patients who underwent curative-intent resection for gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). METHODS: Patients with GET-NETs who underwent curative-intent resection were identified from a multi-center database. The prognostic impact of clinicopathological factors including PNI on post-operative outcomes were evaluated. A novel nomogram was developed and externally validated. RESULTS: A total of 2,099 patients with GEP-NETs were included in the training cohort; 255 patients were in the external validation cohort. Median PNI (n = 973) was 47.4 (IQR 43.1-52.4). At the time of presentation, 1,299 (61.9%) patients presented with some type of clinical symptom. Low-PNI (≤42.2) was associated with gastrointestinal symptoms, as well as nodal metastasis and distant metastasis (all p < 0.05). Patients with a low PNI had a higher incidence of severe (≥Clavien-Dindo grade IIIa: low PNI 24.9% vs. high PNI 15.4%, p = 0.001) and multiple (≥3 types of complications: low PNI 14.5% vs. high PNI 9.2%, p = 0.024) complications, as well as a worse overall survival (OS)(5-year OS, low PNI 73.7% vs. high PNI 88.5%, p < 0.001), and RFS (5-year RFS, low PNI 68.5% vs. high PNI 79.8%, p = 0.008) versus patients with high PNI (>42.2). A nomogram based on PNI, tumor grade and metastatic disease demonstrated excellent discrimination and calibration to predict OS in both the training (C-index 0.748) and two external validation (C-index 0.827, 0.745) cohorts. CONCLUSIONS: Low PNI was common and associated with worse short- and long-term outcomes among patients with GEP-NETs.

Accuracy and Prognostic Impact of Nodal Status on Preoperative Imaging for Management of Pancreatic Neuroendocrine Tumors: A Multi-Institutional Study.

BACKGROUND: We sought to define the accuracy of preoperative imaging to detect lymph node metastasis (LNM) among patients with pancreatic neuroendocrine tumors (pNETs), as well as characterize the impact of preoperative imaging nodal status on survival. METHODS: Patients who underwent curative-intent resection for pNETs between 2000 and 2020 were identified from eight centers. Sensitivity and specificity of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)-CT, and OctreoScan for LNM were evaluated. The impact of preoperative lymph node status on lymphadenectomy (LND), as well as overall and recurrence-free survival was defined. RESULTS: Among 852 patients, 235 (27.6%) individuals had LNM on final histologic examination (hN1). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 12.4%, 98.1%, 71.8%, and 74.4% for CT, 6.3%, 100%, 100%, and 80.1% for MRI, 9.5%, 100%, 100%, and 58.7% for PET, 11.3%, 97.5%, 66.7%, and 70.8% for OctreoScan, respectively. Among patients with any combination of these imaging modalities, overall sensitivity, specificity, PPV, and NPV was 14.9%, 97.9%, 72.9%, and 75.1%, respectively. Preoperative N1 on imaging (iN1) was associated with a higher number of LND (iN1 13 vs. iN0 9, p = 0.003) and a higher frequency of final hN1 versus preoperative iN0 (iN1 72.9% vs. iN0 24.9%, p < 0.001). Preoperative iN1 was associated with a higher risk of recurrence versus preoperative iN0 (median recurrence-free survival, iN1→hN1 47.5 vs. iN0→hN1 92.7 months, p = 0.05). CONCLUSIONS: Only 4% of patients with LNM on final pathologic examine had preoperative imaging that was suspicious for LNM. Traditional imaging modalities had low sensitivity to determine nodal status among patients with pNETs.

An analysis of the relationship between donor and recipient biomarkers and kidney graft function, dysfunction, and rejection.

BACKGROUND: The study aimed to find predictive biomarkers to evaluate donor kidney function to predict graft dysfunction as well as to assess an early signs of acute graft rejection. METHOD: Twenty-seven deceased donors and 54 recipients who underwent a successful kidney transplantation were enrolled in the study. An assessment was made in serum and urine from donors and recipients to measure the following biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase 2 (TIMP-2) and urinary N-acetyl-b-D-glucosaminidase (uNAG). These biomarkers were used to establish a model for predicting a reduced graft function (RGF) classified as either a delayed or slow graft function. RESULT: Our analysis suggest that out of four tested biomarkers, the serum TIMP-2 and uNAG levels of the donors had a predictive value for RGF; the area under the receiver operating characteristic curves (AUROC) of serum TIMP-2 and uNAG were 0.714 and 0.779, respectively. The combined best fitting prediction model of serum TIMP-2, uNAG, and creatinine levels was better in predicting RGF than the serum creatinine level alone. In addition, the recipient serum TIMP-2 level on the third day post-transplantation (D3) was associated with the estimated glomerular filtration rate (eGFR) on the seventh day post-transplantation (D7; OR 1.119, 95% CI 1.016-1.233, p = 0.022). Furthermore, the ROC curve value revealed that the AUROC of TIMP-2 on D3 was 0.99 (95% CI 0.97-1, p < 0.001), and this was the best predictive value of the renal function on D7. CONCLUSIONS: Donor serum TIMP-2 and uNAG levels are useful predictive biomarkers because they can provide the donor-based prediction for RGF.

The global burden of alcoholic liver disease: a systematic analysis of the global burden of disease study 2019.

Alcohol use is a major risk factor for the burden of mortality and morbidity. Alcoholic cirrhosis (AC) and alcoholic liver cancer (ALC) are most important and severe liver disease outcomes caused by alcohol use. The objectives of the current study were to investigate the global prevalence and burden of disease in disability-adjusted life years (DALYs) for AC and ALC, based on data from the Global Burden of Disease (GBD). Incidence, prevalence, death, and DALYs for GBDs in different locations, years, sex, and age groups were estimated using DisMod-MR 2.1 and a generic Cause of Death Ensemble Modeling approach. The correlations between the age-standardized incidence rate or age-standardized death rate and gender, sociodemographic index (SDI), and alcohol usage were conducted by Generalized Linear Models. Globally, the changes of age-standardized rates of indicators were not much significant over the 30-year period. However, the changes varied widely across regions. Central Asia and East Europe contributed the highest age-standardized incidence, prevalence, death, and DALYs and increased sharply by past 30 years. Generalized Linear Models (GLMs) showed male gender as a risk factor of AC, with the relative risk of incidence of 1.521 and relative risk of death of 1.503. Globally, there were improvements in overall health with regard to GBDs over the 30 years. However, the prevention of AC and ALC should be promoted in middle and middle-high SDI regions, especially Central Asia and East Europe, whereas more medical resources should be provided to improve treatment levels in low SDI region.

Multi-motor position synchronization control method based on non-singular fast terminal sliding mode control.

In order to improve the position high-precision synchronization performance of multi-motor synchronous control, a multi-motor position synchronization control method based on non-singular fast terminal sliding mode control (NFTSMC) combined with an improved deviation coupling control structure (Improved Deviation Coupling Control(IDCC), NFTSMC+IDCC). Firstly, this paper designs a sliding mode controller using a non-singular fast terminal sliding mode surface with a Permanent Magnet Synchronous Motor (PMSM) as the control object. Secondly, the deviation coupling is improved to enhance the coupling between multiple motors and achieve position synchronization. Finally, the simulation results show that the total error of multi-motor position synchronization under NFTSMC control is 0.553r in the simulation of multi-motor synchronization control under the same working conditions, which is 2.873r and 1.772r less than that of SMC and FTSMC in terms of speed error, and the anti-disturbance performance is 83.68% and 76.22% higher than that of both of them, respectively. In the subsequent simulation of the improved multi-motor position synchronization structure, the total error of the multi-motor position is in the range of 0.56r-0.58r at three speeds, which is much smaller than the synchronization error under the Ring Coupling Control (RCC) structure and Deviation Coupling Control (DCC) structure, showing a better The synchronization error is much smaller than that of the RCC structure and DCC structure, which shows better position synchronization performance. Therefore, the multi-motor position synchronization control method proposed in this paper has a good position synchronization effect and achieves the control effect of small displacement error and fast convergence of the multi-motor position synchronization control system after being disturbed, the control performance is significantly improved.

Development and Validation of an α-Fetoprotein Tumor Burden Score Model to Predict Postrecurrence Survival among Patients with Hepatocellular Carcinoma.

BACKGROUND: The purpose of this study is to establish a prognostic model to predict postrecurrence survival (PRS) probability after initial resection of hepatocellular carcinoma (HCC). STUDY DESIGN: Patients with recurrent HCC after curative resection were identified through a multicenter consortium (training cohort, TC); data were from a separate institution were used as validation cohort (VC). The α-fetoprotein (AFP) tumor burden score (ATS) was defined as the distance from the origin on a 3-dimensional Cartesian coordinate system that incorporated 3 variables: largest tumor diameter ( x axis), number of tumors ( y axis), and ln AFP ( z axis). ATS was calculated using the Pythagorean theorem: ATS 2 = (largest tumor diameter) 2 + (number of tumors) 2 + (ln AFP) 2 , where ATS d and ATS r represent ATS at the time of initial diagnosis and at the time of recurrence, respectively. The final model was ATS m = ATS d + 4 × ATS r . Predictive performance and discrimination of the ATS model were evaluated and compared with traditional staging systems. RESULTS: The ATS model demonstrated strong predictive performance of PRS in both the TC (area under the curve [AUC] 0.70) and VC (AUC 0.71). An ATS-based nomogram was able to stratify patients accurately into low- and high-risk categories relative to PRS (TC: ATS m ≤ 27, 74.9 months vs. ATS m ≥ 28, 23.3 months; VC: ATS m ≤ 27, 59.4 months vs. ATS m ≥ 28, 15.1 months; both p < 0.001). The ATS model predicted PRS among patients undergoing curative or noncurative treatment of HCC recurrence (both p < 0.05). Of note, the ATS model outperformed the Barcelona Clinic Liver Cancer (BCLC), China Liver Cancer (CNLC), and American Joint Committee on Cancer (AJCC) staging systems relative to 1-, 2-, 3-, 4- and 5-year PRS (AUC 0.70, vs. BCLC, AUC 0.50, vs. CNLC, AUC 0.54, vs. AJCC, AUC 0.51). CONCLUSIONS: The ATS model had excellent prognostic discriminatory power to stratify patients relative to PRS.

TRIB3-Regulated Akt Signal Pathway Affects Trophoblast Invasion in the Development of Preeclampsia.

OBJECTIVE: The aim of the study is to explore the mechanism of tribbles pseudokinase 3 (TRIB3)-regulated Akt pathway in the development of preeclampsia (PE). STUDY DESIGN: TRIB3 expression in the placenta of PE patient was determined by quantitative reverse transcriptase polymerase chain reaction and western blotting. Then HTR-8/SVneo or JEG-3 cells were transfected and divided into Mock, Control siRNA, TRIB3 siRNA-1, and TRIB3 siRNA-2 groups. Cell proliferation, invasion, and migration were determined by MTT assay, Transwell assay, and wound healing test, while the expression of TRIB3 and Akt pathway was measured by western blotting. PE rats were treated with TRIB3 siRNA, and blood pressure, 24-hour urinary protein, as well as serum levels of sFlt-1 and vascular endothelial growth factor (VEGF) were measured. RESULTS: The placenta of PE patients presented with increased TRIB3 expression. In comparison with Mock group, the proliferation, invasion, and migration of HTR-8/SVneo and JEG-3 cells in TRIB3 siRNA-1 group and TRIB3 siRNA-2 group increased, with decreased TRIB3 expression but enhanced expression of p-Akt/Akt, MMP-2, and MMP-9. Rats in PE group showed increases in mean arterial pressure, SBP, 24-hour urinary protein, and serum sFlt-1 levels, but decreases in serum VEGF levels, fetal weight, and placental efficiency. Moreover, TRIB3 expression was upregulated, while p-Akt/Akt was downregulated in the placenta of rats in PE group. However, indicators above were significantly improved in rats treated with TRIB3 siRNA. CONCLUSION: TRIB3 was upregulated in the PE placenta, while silencing TRIB3 activated the Akt signaling pathway to promote the invasion and migration of trophoblast both in vitro and in vivo and ameliorated the development of PE symptoms in the PE rat model. KEY POINTS: · The TRIB3 expression was increased in the placenta of PE patient. · Silencing TRIB3 activates Akt signal pathway.. · Silencing TRIB3 improves the pathological process of preeclampsia rat..

Impact of adjuvant therapy on outcomes after curative-intent resection for distal cholangiocarcinoma.

BACKGROUND: The benefit of adjuvant therapy (AT) after curative resection of distal cholangiocarcinoma (DCC) remains unclear. The objective of the current study was to investigate the impact of AT on long-term survival of patients who underwent curative-intent resection for DCC. METHODS: Patients who underwent curative-intent resection for DCC between 2000 and 2020 were identified from a multi-institutional database. The primary outcomes included overall (OS) and recurrence-free survival (RFS). RESULTS: Among 245 patients, 150 (61.2%) patients received AT (chemotherapy alone: n = 43; chemo- and radiotherapy: n = 107) after surgical resection, whereas 95 (38.8%) patients underwent surgery only. Patients who received AT were younger, and more likely to have an advanced tumor with the presence of perineural invasion (PNI), lymph node metastasis (LNM), lymph-vascular invasion, and higher T categories (all p < 0.05). Overall, there was no difference in OS (median, surgery + AT 25.5 vs. surgery alone 24.5 months, p = 0.27) or RFS (median, surgery + AT 15.8 vs. surgery alone 18.9 months, p = 0.24) among patients who did versus did not receive AT. In contrast, AT was associated with improved long-term survival among patients with PNI (median OS, surgery + AT 25.9 vs. surgery alone 17.8 months, p = 0.03; median RFS, surgery + AT 15.9 vs. surgery alone 11.9 months, p = 0.04) and LNM (median, surgery + AT 20.0 vs. surgery alone 17.8 months, p = 0.03), but not among patients with no PNI or LNM (all p > 0.1). CONCLUSIONS: AT was commonly utilized among patients with DCC. Patients with more advanced disease, including the presence of PNI or LNM, benefited the most from AT with improved long-term outcomes among this subset of patients.