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Background The utility of an electrophysiologic study (EPS) in the risk stratification of CS patients is not clear. We conducted a systemic review and meta-analysis to evaluate the utility of EPS in the risk stratification of CS patients. Methods We searched PubMed, EMBASE, and Scopus databases from their inception to 12/4/2020 with search terms “Cardiac sarcoidosis” And “Electrophysiological studies OR ablation”. The first and second authors reviewed all the studies. We extracted the data of positive and negative EPS, and outcomes defined as ventricular arrhythmias, implantable cardioverter defibrillator therapy, death, left ventricular assist device placement, or heart transplantation. Risk of bias assessment was done by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Subgroup analysis of patients with left ventricular ejection fraction (LVEF) >35%, and probable CS, no prior VT, and LVEF >35% were performed. Results We found 544 articles after removing duplicates. A total of 52 full articles were reviewed, and eight studies were included in the meta-analysis. The pooled sensitivity and specificity (95% confidence interval) of EPS in predicting clinical outcomes were 0.70 (0.51–0.85) and 0.93 (0.85–0.97), respectively. Subgroup analysis of patients with LVEF >35% resulted in pooled sensitivity of 0.63 (0.29–0.88) and pooled specificity of 0.97 (0.92–0.99), and subgroup analysis of patients with probable CS, no prior VT, and LVEF >35% resulted in pooled sensitivity of 0.71 (0.33–0.93) and pooled specificity of 0.96 (0.88–0.99) in predicting clinical outcomes. Conclusions EPS is an effective risk stratification tool in patients with CS across all subgroups with high sensitivity and specificity.

We completed a systematic review of Takotsubo syndrome (TTS) cases reported during the coronavirus disease 2019 (COVID-19) pandemic and performed clustering and feature importance analysis and statistical testing for independence on the demographic, clinical, and imaging parameters. Compared with the data before the COVID-19 pandemic, TTS was increasingly diagnosed in physical stress (mostly COVID-19 pneumonia)-triggered male patients without psychiatric/neurologic disorders, warranting further investigation to establish new reference criteria to improve diagnostic specificity. In clustering analysis, sex and inpatient mortality primarily contributed to the automated classification of the TTS. Both sex and inpatient mortality had essential correlations with COVID-19 infection/pneumonia. There is effect modification of sex on outcomes in patients with COVID-19 infection and TTS, with male patients having significantly worse inpatient mortality. Meanwhile, significantly more male patients with TTS were classified as high risk according to International Takotsubo Registry prognostic scores, suggesting that male COVID-19/TTS survivors will likely have worse long-term outcome.

There is no established screening approach for hypertrophic cardiomyopathy (HCM). We recently developed an artificial intelligence (AI) model for the detection of HCM based on the 12‑lead electrocardiogram (AI-ECG) in adults. Here, we aimed to validate this approach of ECG-based HCM detection in pediatric patients (age ≤ 18 years).We identified a cohort of 300 children and adolescents with HCM (mean age 12.5 ± 4.6 years, male 68%) who had an ECG and echocardiogram at our institution. Patients were age- and sex-matched to 18,439 non-HCM controls. Diagnostic performance of the AI-ECG model for the detection of HCM was estimated using the previously identified optimal diagnostic threshold of 11% (the probability output derived by the model above which an ECG is considered to belong to an HCM patient).Mean AI-ECG probabilities of HCM were 92% and 5% in the case and control groups, respectively. The area under the receiver operating characteristic curve (AUC) of the AI-ECG model for HCM detection was 0.98 (95% CI 0.98-0.99) with corresponding sensitivity 92% and specificity 95%. The positive and negative predictive values were 22% and 99%, respectively. The model performed similarly in males and females and in genotype-positive and genotype-negative HCM patients. Performance tended to be superior with increasing age. In the age subgroup5 years, the test's AUC was 0.93. In comparison, the AUC was 0.99 in the age subgroup 15-18 years.A deep-learning, AI model can detect pediatric HCM with high accuracy from the standard 12‑lead ECG.

BACKGROUND People with bipolar disorder (BD) frequently struggle with the recurrence of affective symptoms. However, the interplay between coping mechanism and positive mood state remains under-researched. AIM To explore the associations among behavioral approach system (BAS) sensitivity level, coping, and positive mood states among people with BD. METHODS Using a cross-sectional study design, 90 participants with BD were presented with four BAS-activating life event scenarios and assessed with regard to their BAS trait sensitivity, coping flexibility, and mood states. A hierarchical clustering method was used to identify different groups with different styles of coping. Multiple hierarchical regression analyses were conducted to examine the mediating and moderating roles of different components of coping on mood states. RESULTS A three-cluster solution was found to best fit the present data set. The findings showed that a low mass of coping combined with low BAS sensitivity level protects people with BD from detrimentally accentuating mood states when they encounter BAS-activating life events. Moreover, coping flexibility is demonstrated to mediate and moderate the relationships between BAS sensitivity level and mood states. Specifically, subduing the perceived controllability and reducing the use of behavioral-activation/emotion-amplifying coping strategies could help buffer the effect of positive affect. CONCLUSION The judicious use of coping in emotion regulation for people with BD when encountering BAS-activating life events was indicated. Practical applications and theoretical implications are highlighted.

Purpose To investigate and identify first-trimester fasting plasma glucose (FPG) is related to gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes in Shenzhen population. Methods We used data of 48,444 pregnant women that had been retrospectively collected between 2017 and 2019. Logistic regression analysis was used to evaluated the associations between first-trimester FPG and GDM and adverse pregnancy outcomes, and used to construct a nomogram model for predicting the risk of GDM. The performance of the nomogram was evaluated by using ROC and calibration curves. Decision curve analysis (DCA) was used to determine the clinical usefulness of the first-trimester FPG by quantifying the net benefits at different threshold probabilities. Results The mean first-trimester FPG was 4.62 ± 0.42 mmol/L. A total of 6998 (14.4%) pregnancies developed GDM.489(1.01%) pregnancies developed polyhydramnios, the prevalence rates of gestational hypertensive disorder (GHD), cesarean section, primary cesarean section, preterm delivery before 37 weeks (PD) and dystocia was 1130 (2.33%), 20,426 (42.16%), 7237 (14.94%), 2386 (4.93%), and 1865 (3.85%), respectively. 4233 (8.74%) of the newborns were LGA, and the number of macrosomia was 2272 (4.69%), LBW was 1701 (3.51%) and 5084 (10.49%) newborns had admission to the ICU, which all showed significances between GDM and non-GDM groups (all P 1, all P P P Conclusions FPG in the first trimester was an independent risk factor for GDM which can be used as a screening test for identifying pregnancies at risk of GDM and adverse pregnancy outcomes.

Aim: This study aimed to investigate the effects of LINC00240/miR-155/Nrf2 axis on trophoblast function and macrophage polarization in the pathogenesis of preeclampsia. Methods: Bindings between LINC00240, miR-155 and Nrf2 were validated by dual luciferase reporter assay or RNA-immunoprecipitation method. Cell proliferation, migration, invasion, and pyroptosis were detected by CCK-8, clone formation, wound healing, Transwell system and flow cytometry, respectively. Macrophage polarization was tested by flow cytometry. LINC00240, miR-155 and Nrf2 levels, and oxidative stress and pyroptosis related-protein levels in in vitro and in vivo preeclampsia model were analyzed by qPCR, western blot or ELISA assays. Blood pressure, urine protein level, liver and kidney damages, and trophoblast marker in placenta tissues were further studied in vivo. Results: Placenta tissues from preeclampsia patients and animals showed decreased LINC00240 and Nrf2 expressions and increased miR-155 expression. LINC00240 directly bound and inhibited expression of miR-155, which then inhibited oxidative stress-induced pyroptosis, promoting proliferation, migration and invasion abilities of trophoblasts, and M2 macrophage polarization. Inhibition of miR-155 led to the increased Nrf2 expression and similar changes as LINC00240 in trophoblast function and macrophages polarization. Overexpression of LINC00240 in an in vivo preeclampsia model decreased blood pressure, urine protein, liver and kidney damages, increased fetal weight and length, and also induced trophoblast function and M2 macrophage polarization. Conclusion: LINC00240 inhibited symptoms of preeclampsia through regulation on miR-155/Nrf2 axis, which suppressed oxidative stress-induced pyroptosis to improve trophoblast functions and polarization of M2 macrophages. LINC00240 could be a potential therapeutic target for preeclampsia. Funding Statement: This work was supported by A study on serum proteomics and clinical application of pregnancy induced hypertension based on iTRAQ technology（ SB201901087） and Relationship between fibronectin and hypertensive disorder complicating pregnancy and its clinical application (192102310335). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Written informed consent was collected from all participants before the procedure. The research protocol was approved by the Ethical Committee of the Henan Provincial People’s Hospital (Zhengzhou, Henan, China). All the animal experiment procedures were approved by the Animal Ethics Committee of Henan Provincial People’s Hospital (Zhengzhou, Henan, China).

Zhenzhou Xu,* Liang Huang,* Tao Dai,* Xiaming Pei, Longzheng Xia, Gongqian Zeng, Mingji Ye, Kan Liu, Fuhua Zeng, Weiqing Han, Shusuan Jiang Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, 410013, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenzhou Xu; Shusuan JiangDepartment of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, 283# Tongzipo Road, Yuelu District, Changsha, Hunan, 4100013, People’s Republic of ChinaTel +86 18874728621; +86 18608408523Fax +86 73189762270Email xuzhenzhou@hnca.org.cn; jiangshusuan@hnca.org.cnBackground: Almost all metastatic hormone-sensitive prostate cancers (mHSPC) will develop into metastatic castration-resistant prostate cancer (mCRPC) after androgen deprivation therapy (ADT). The expression level of squalene monooxygenase (SQLE) is increased in CRPC cells and regulates cholesterol metabolism. This study verified the biological function and mechanisms of SQLE in CRPC.Methods: The expression of SQLE in human prostate cancer cells was overexpressed or silenced and its efficacy on cell survival was determined by the MTS test. Energy metabolism phenotype test was evaluated by XF real-time ATP rate assay, XF cell mitochondrial stress test, XF glycolysis stress test and XF mito fuel flex test. Cell migration and invasion were evaluated by colony formation assays and transwell assays; the expression of mRNA and protein was assessed by RT-qPCR and Western blot, respectively. Moreover, BALB/c nude mice model was performed to evaluate the lymph node metastasis.Results: In our study, we found that the expression level of SQLE was significantly increased in bicalutamide-resistant-C4-2B cells compared to LNCaP cells. SQLE knockdown partly restored the sensitivity of drug-resistant cells to bicalutamide and reduced lymph node metastasis by inhibiting fatty acid oxidation in mitochondria. We also found that terbinafine, the specific inhibitor of SQLE, can enhance the sensitivity of prostate cancer cells to bicalutamide.Conclusion: Our study revealed that SQLE is involved in the progression of castration resistance in CRPC through mediating metabolic reprogramming, presenting SQLE as a new target for the treatment of mCRPC.Keywords: SQLE, bicalutamide, CRPC, ADT, lymph node metastasis

Background Robot-assisted thrombectomy (RAT) for inferior vena cava (IVC) thrombus (RAT-IVCT) is being increasingly reported. However, the techniques and indications for robot-assisted cavectomy (RAC) for IVC thrombus are not well described. Objective To develop a decision-making program and analyze multi-institutional outcomes of RAC-IVCT versus RAT-IVCT. Design, setting, and participants Ninety patients with renal cell carcinoma (RCC) with level II IVCT were included from eight Chinese urological centers, and underwent RAC-IVCT (30 patients) or RAT-IVCT (60 patients) from June 2013 to January 2019. Surgical procedure The surgical strategy was based on IVCT imaging characteristics. RAT-IVCT was performed with standardized cavotomy, thrombectomy, and IVC reconstruction. RAC-IVCT was mainly performed in patients with extensive IVC wall invasion when the collateral blood vessels were well-established. For right-sided RCC, the IVC from the infrarenal vein to the infrahepatic veins was stapled. For left-sided RCC, the IVC from the suprarenal vein to the infrahepatic veins was removed and caudal IVC reconstruction was performed to ensure the right renal vein returned through the IVC collaterals. Measurements Clinicopathological, operative, and survival outcomes were collected and analyzed. Results and limitations All procedures were successfully performed without open conversion. The median operation time (268 vs 190 min) and estimated blood loss (1500 vs 400 ml) were significantly greater for RAC-IVCT versus RAT-IVCT (both p Conclusions RAC-IVCT or RAT-IVCT represents an alternative minimally invasive approach for selected RCC patients with level II IVCT. Selection of RAC-IVCT or RAT-IVCT is mainly based on preoperative IVCT imaging characteristics, including the presence of IVC wall invasion, the affected kidney, and establishment of the collateral circulation. Patient summary In this study we found that robotic surgeries for level II inferior vena cava thrombus were feasible and safe. Preoperative imaging played an important role in establishing an appropriate surgical plan.

The impact of right ventricular impairment (RVI) on the morbidity and mortality of patients with Takotsubo syndrome (TTS) is well-debated. We conducted a meta-analysis to evaluate the mortality and morbidity risk associated with RVI compared with those without RVI in patients with TTS. A comprehensive search was performed in PubMed and Embase from inception to April 19, 2019. Our primary outcome of interest was in-hospital and long-term mortality. Other outcomes of interest were acute heart failure, left ventricular systolic function, tricuspid and mitral regurgitation, and length of hospital stay (LOS). We are reporting our outcomes as a cumulative odds ratio (OR). After an initial search, 10 studies with 1210 subjects were included in the quantitative analysis. Mean follow-up was 31 months. The odds of in-hospital and long-term mortality in TTS patients with and without RVI were not significantly different (p = 0.13 and 0.40). In TTS patients without RVI, the odds of acute heart failure, and mitral and tricuspid regurgitation were significantly lower at an OR of 0.26 (p

Background: To examine the impact of the Mayo adhesive probability (MAP) score on the surgical complexity of exposing the tumor during laparoscopic partial nephrectomy (LPN). Patients and Methods: ...

Intraoperative radiotherapy (IORT) has emerged as an alternative to whole-breast external beam radiotherapy (EBRT) for early breast cancer. This study aimed to investigate the risk factors for survival after IORT or whole-breast EBRT in breast cancer patients. Breast cancer patients undergoing IORT or whole-breast EBRT were included from the surveillance, epidemiology, and end results database. Risk factors for overall survival (OS) and cancer-specific survival (CSS) were identified by Cox proportional hazards regression analysis. The IORT and EBRT groups did not differ significantly in OS and CSS. T2 stage (tumor size > 2 cm) was associated with poorer OS (aHR 3.49, 95% CI 1.05–11.62, P = 0.042), whereas ER-positive tumors were associated with better OS (aHR 0.26, 95% CI 0.09–0.76, P = 0.014). IORT was not inferior than EBRT considering the OS and CSS in the short-term follow-up of early breast cancer. It may be a reasonable alternative to EBRT for early breast cancer in select patients with favorable tumor size and receptor status, given the need for long-term monitoring of local control and radiation toxicity.

Increased levels of mitochondrial coupling factor 6 (CF6) are present in the peripheral blood of patients with preeclamptic pregnancies, and are particularly evident in cases of early-onset or severe preeclampsia. The present study examined the location and expression levels of CF6 in the placental tissue and its effect on the biological behavior of trophoblast cells. Placental tissue microarrays, including placental villous cytotrophoblast and extravillous cytotrophoblast microarrays, were used to detect the location and relative expression levels of CF6 in the placenta using immunohistochemistry. It was found that CF6 was expressed in both the normal and preeclamptic placenta, but its levels were higher in the preeclamptic tissues. In addition, the effects of the hypoxic environment on the biological behaviors of trophoblast cells were investigated in the JAR and JEG-3 cell lines. Following induction of hypoxia, the expression levels of CF6 were increased. Moreover, exogenous addition of human recombinant CF6 attenuated cell invasion, but exerted no effect on cell proliferation. At the molecular level, the expression levels of MMP-2 were decreased and were accompanied with a reduction in cell invasion following addition of exogenous CF6. In conclusion, the increased expression levels of CF6 and its effects in reducing the invasive abilities of trophoblast cells may be involved in the pathogenesis of severe preeclampsia.

Poorly differentiated gastric adenocarcinoma is commonly associated with lymph node metastasis, peritoneal spread, and liver metastasis but rarely with intraintestinal metastasis. Most patients with metastatic gastric carcinoma are unable to undergo surgical treatment and have a poor prognosis. A 42-year-old man with hunger-related abdominal pain was diagnosed as having gastric cancer. After the first surgery (distal partial gastrectomy) and the second surgery (gastric stump carcinoma (GSC) resection), the patient suffered repeated multiple intracolonic metastases and underwent three additional resection operations. The patient survived for 154 months after the first operation. In patients with gastric carcinoma that metastasizes to the colonic lumen, radical resection, if possible, can extend survival. Once patients develop extensive extraintestinal metastasis, radical resection cannot be performed, and patients often exhibit a poor prognosis.

Pulmonary fibrosis is the primary reason for mortality in patients with paraquat (PQ) poisoning. Our previous study demonstrated that epithelial-mesenchymal transition (EMT) had a role in PQ-induced pulmonary fibrosis. However, the role of endoplasmic reticulum (ER) stress in PQ-induced EMT remains clear. The present study aimed to determine the role of ER stress in EMT in PQ-induced pulmonary fibrosis. A549 and RLE-6TN cells were incubated with LY294002 (a PI3K inhibitor) or transfected with protein kinase RNA-like ER kinase (PERK) small interfering RNA (si) for 24 h prior to being exposed to PQ. Next, the expression levels of ER stress-related proteins, PI3K/AKT/GSK-3β signaling pathway-related proteins and EMT-related markers were analyzed by performing western blotting, reverse transcription-quantitative PCR and immunofluorescence assays. The results of the present study revealed that the protein expression levels of PERK, phosphorylated (p)-PERK, p-eukaryotic initiation factor 2 (eIF2)α were significantly upregulated in the PQ group, whereas p-PI3K, p-AKT and p-GSK-3β were significantly upregulated in the sicontrol + PQ group compared with the sicontrol group. In vitro, following transfection with siPERK or treatment with the PI3K inhibitor, the protein expression levels of E-cadherin (an epithelial marker) were upregulated, whereas the protein expression levels of α-SMA (a mesenchymal marker) were downregulated. Immunofluorescence analysis revealed that the levels of E-cadherin were markedly upregulated, whereas the levels of α-SMA were notably downregulated following transfection with siPERK compared with the sicontrol group. The results of wound healing assay demonstrated that cell migration in the siPERK + PQ group was markedly decreased compared with the sicontrol + PQ group. These indicated that PQ-induced EMT was suppressed after silencing PERK. The expression levels of p-GSK-3β, p-AKT and p-PI3K were also markedly downregulated in the siPERK + PQ group compared with the sicontrol + PQ group. In conclusion, the findings of the present study suggested that ER stress may promote EMT through the PERK signaling pathway in PQ-induced pulmonary fibrosis. Thus, ER stress may represent a potential therapeutic target for PQ-induced pulmonary fibrosis.

Targeting androgen receptor (AR) has been shown to be promising in treating glioblastoma (GBM) in cell culture and flank implant models but the mechanisms remain unclear. AR antagonists including enzalutamide are available for treating prostate cancer patients in clinic and can pass the blood–brain barrier, thus are potentially good candidates for GBM treatment but have not been tested in GBM orthotopically. Our current studies confirmed that in patients, a majority of GBM tumors overexpress AR in both genders. Enzalutamide inhibited the proliferation of GBM cells both in vitro and in vivo. Although confocal microscopy demonstrated that AR is expressed but not specifically in glioma cancer stem cells (CSCs) (CD133+), enzalutamide treatment significantly decreased CSC population in cultured monolayer cells and spheroids, suppressed tumor sphere-forming capacity of GBM cells, and downregulated CSC gene expression at mRNA and protein levels in a dose- and time-dependent manner. We have, for the first time, demonstrated that enzalutamide treatment decreased the density of CSCs in vivo and improved survival in an orthotopic GBM mouse model. We conclude that AR antagonists potently target glioma CSCs in addition to suppressing the overall proliferation of GBM cells as a mechanism supporting their repurposing for clinical applications treating GBM.

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/., Background: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes. Methods: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients. Results: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients. Conclusion: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers., Open Access funding provided by Universität Zürich. CT has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme and the Swiss Heart Foundation. L.S.M. has been supported by EU HORIZON 2020 (SILICOFCM ID777204). J.R.G has received a grant “Filling the gap” from the University of Zurich. The InterTAK Registry is supported by The Biss Davies Charitable Trust.

© 2019 The Authors European Journal of Heart Failure © 2019 European Society of Cardiology, Recent evidence suggests comparable in‐hospital and long‐term outcomes between takotsubo syndrome (TTS) and acute coronary syndrome. Medical scoring systems are practical tools for decision making and prognostic assessment. However, TTS‐specific scoring systems for risk stratification have not yet been established. Recently, classification based on triggering conditions proved useful in predicting adverse outcomes in TTS (InterTAK Classification).1 Since clinical parameters other than triggering conditions can be associated with adverse outcomes in TTS, such as systolic blood pressure and heart rate, the present study aimed to establish a scoring system combining triggering factors with other important but easily‐ obtainable clinical parameters of daily clinical practice., C.T. has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme and the Swiss Heart Foundation. L.S.M. was supported by EU HORIZON 2020 (SILICOFCM ID777204). The InterTAK Registry is supported by the Biss Davies Charitable Trust.

BACKGROUND This article presents our experience in managing a rare kidney tumor - reninoma - by analyzing a relatively large series of cases from a single center. MATERIAL AND METHODS Nine cases of reninoma were reviewed. Clinical manifestations, imaging examinations, laboratory examinations, perioperative data, and pathological findings were summarized. A 58.8-month follow-up was performed to evaluate patient survival and recrudescence. RESULTS The main clinical manifestations were hypertension, hypokalemia, headache, dizziness, nausea, vomiting, palpation, and sweating. Three patients had hypertensive end-organ damage, including brain hemorrhage, gestation termination, and grade III ocular fundus changes. All patients underwent retroperitoneal laparoscopic partial nephrectomy successfully. The mean warm ischemic time was 23.4 min. The median operation time was 95.1 min, with a median estimated blood loss of 60 ml. The median hospital stay was 6 days. No serious intraoperative or postoperative complications occurred. The histology and electron microscopy findings confirmed the diagnosis of reninoma in all cases. After 58.8 months of follow-up, symptoms involving hypertension were relieved in all patients, and no tumor recurrence or metastasis was detected. CONCLUSIONS Reninoma may have severe consequences despite being a benign tumor. Retroperitoneal laparoscopic partial nephrectomy is a feasible and effective method for the surgical removal of reninoma. Multidisciplinary cooperation plays an important role in improving the diagnosis and enabling the early surgical treatment of reninoma. Especially in cases of reninoma with moderate and high RENAL scores, an accurate diagnosis of reninoma based on multidisciplinary cooperation facilitates the selection of less invasive surgical approaches.

Although anti-PD-1 immunotherapy is widely used to treat melanoma, its efficacy still has to be improved. In this work, we present a therapeutic method that combines immunotherapy and starvation therapy to achieve better antitumor efficacy. We designed the CMSN-GOx method, in which mesoporous silica nanoparticles (MSN) are loaded with glucose oxidase (GOx) and then encapsulate the surfaces of cancer cell membranes to realize starvation therapy. By functionalizing the MSN's biomimetic surfaces, we can synthesize nanoparticles that can escape the host immune system and homologous target. These attributes enable the nanoparticles to have improved cancer targeting ability and enrichment in tumor tissues. Our synthetic CMSN-GOx complex can ablate tumors and induce dendritic cell maturity to stimulate an antitumor immune response. We performed an in vivo analysis of these nanoparticles and determined that our combined therapy CMSN-GOx plus PD-1 exhibits a better antitumor therapeutic effect than therapies using CMSN-GOx or PD-1 alone. Additionally, we used the positron emission tomography imaging to measuring the level of glucose metabolism in tumor tissues, for which we investigate the effect with the cancer therapy in vivo.

Background In patients with acute anterior myocardial infarction (MI), sometimes an “apical ballooning” contractile dysfunction pattern that exceeds factual myocardial injury is identified in the ventriculography and bedside echocardiography. The hemodynamic consequences/sequela of this “Tako-tsobu effect” has not been well delineated. Of note, this anatomic imaging finding often misleads frontline physicians who assume reciprocal causation of persistent cardiac pump failure and ventricular pressure overload. Methods and results Using real-time myocardial perfusion contrast echocardiography (MCE), we investigated myocardial (microvascular) perfusion in 60 patients after acute MI and coronary revascularization. Twenty-eight percent of the studied patients showed significantly mismatched myocardial perfusion and contractile defects. In these patients, an integrated imaging assessment with coronary angiography/ventriculography, deformation echocardiography, and MCE proved that the myocardial mechanic abnormalities significantly exceeded the defected perfusion areas. Compared with 72% of the patients without perfusion-contractility mismatch, apparently worse systolic functions (left ventricular ejection, wall motion score, and systolic longitudinal strain) in these patients did not change diastolic ventricular filling pressures (E/E′ and E/A) or hemodynamic consequences/adverse events. Both systolic and diastolic functions in patients with perfusion-contractility mismatch appeared to be comparable with those in patients with Tako-tsubo syndrome. Conclusions Real-time MCE identifies discrepant myocardial microvascular perfusion and mechanics in patients with acute MI. The “Tako-tsubo effect” in patients with perfusion-contractility mismatch does not cause diastolic filling pressure change or worse hemodynamic consequence/cardiac event.

© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License., Aims: Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes. Methods and results: Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In-hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long-term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long-term mortality (hazard ratio 2.12, 95% confidence interval 1.33-3.38; P = 0.002). Conclusions: The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in-hospital course and a worse long-term outcome., C. T. has been supported by the H.H. Sheikh Khalifa binHamad Al-Thani Research Programme and the Swiss HeartFoundation. The InterTAK Registry is supported by the BissDavies Charitable Trust. L. S. M. has been supported by EUHORIZON 2020(SILICOFCM ID777204)

Copyright © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes., Background Atrial fibrillation (AF) is a major risk factor for mortality. The prevalence, clinical correlates, and prognostic impact of AF in Takotsubo syndrome (TTS) have not yet been investigated in a large patient cohort. This study aimed to investigate the prevalence, clinical correlates, and prognostic impact of AF in patients with TTS. Methods and Results Patients with TTS were enrolled from the International Takotsubo Registry, which is a multinational network with 26 participating centers in Europe and the United States. Patients were dichotomized according to the presence or absence of AF at the time of admission. Of 1584 patients with TTS, 112 (7.1%) had AF. The mean age was higher (P

PurposeThis study aimed to assess efficacy and safety of anlotinib as a first- or second-line treatment for advanced or metastatic hepatocellular carcinoma (aHCC) and to identify the predictive plasma cytokines on efficacy of anlotinib.MethodsIt was a phase II clinical study. Patients with aHCC were recruited from October 2016 to April 2019 and divided into two cohorts according to previous tyrosine kinase inhibitors (TKIs) therapy. Those without or with prior TKIs were in Cohort 1 or 2, respectively. All patients took anlotinib (12 mg/day, Day1–14, 3 weeks per cycle). The primary endpoint was 12-week progression-free survival (PFS) rate. Relationship between the series plasma cytokine level and the efficacy of anlotinib was analyzed.ResultsEnrolled 26 patients in Cohort 1 and 24 in Cohort 2. In Cohort 1, the 12-week PFS rate was 80.8% [95% confidence interval (CI); 59.8%–91.5%] and median time to progression (TTP) was 5.9 months (95% CI 4.8–6.9). In Cohort 2, the 12-week PFS rate and median TTP was 72.5% (95% CI 48.7%–86.6%) and 4.6 months (95% CI 2.7–10.0), respectively. The median TTP on patients with a baseline plasma level of CXCL1 (C-X-C motif chemokine ligand 1) less than 7.6 ng/μl was significantly longer in both cohorts. The most common grade 3–5 adverse events were hypertension (8%), diarrhea (8%) and hand-foot syndrome (6%).ConclusionAnlotinib showed promising efficacy and safety as a first- or second-line treatment with a continuous TKIs treatment strategy in aHCC. The plasma CXCL1 might be a predictor for the efficacy of anlotinib.

Background A systematic review and meta-analysis was performed to compare the clinicopathological features and survival outcomes between sarcomatoid variant (SV)-urothelial carcinoma of the bladder (UCB) and conventional UCB (C-UCB). Methods A comprehensive search of PubMed, Embase, and Cochrane Library was performed. Endpoints included clinicopathological features and survival outcomes (overall survival [OS], cancer-specific survival [CSS], and progression-free survival [PFS]). The survival benefits of neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC) for SV-UCB also have been studied. Results A total of 8 observational studies were included. Patients with SV-UCB had a higher rate of ≥ stage pT3 (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.64–2.59; p Conclusions Compared to C-UCB, SV-UCB was associated with more advanced disease and more inferior OS and CSS. NAC and AC had no survival benefit for SV-UCB.

Objectives/hypothesis The individualized risk of airway obstruction after head and neck cancer surgery is unclear, especially oral and oropharyngeal cancer. The study aimed to establish an individualized predictive model for the necessity of temporary tracheotomy in these patients. Methods Patients who underwent oral and oropharyngeal cancer surgery from 1999 to 2019 were retrospectively reviewed. A nomogram was developed and validated in patients treated from 1999 to 2009 and 2010 to 2019, respectively. Results In total, 1551 patients were included. Oropharyngeal cancer, large tumor, midline crossing, preoperative radiation, mandibulectomy, flap reconstruction, and neck dissection were independent risk factors of postoperative airway obstruction in the training group (n = 707). A nomogram incorporating these factors had a C-index of 0.931 and was validated in the testing group (n = 844) (C-index, 0.918). Good calibration curves were observed in both groups. Conclusions The nomogram successfully predicted the individual risk of postoperative airway obstruction for patients with oral and oropharyngeal cancer. Level of evidence 4. Laryngoscope, 131:E1489-E1495, 2021.

Background Myocardial infarction can be a trigger of Takotsubo syndrome. We recently characterized imaging features of acute myocardial infarction-induced Takotsubo syndrome (“Takotsubo effect”). In this study, we investigate diagnostic and prognostic implications of Takotsubo effect in patients with anterior wall ST-segment elevation myocardial infarction. Methods We enrolled 111 consecutive patients who developed anterior wall ST-segment elevation myocardial infarction and received percutaneous coronary intervention, and studied systolic/diastolic function, hemodynamic consequences, adverse cardiac events, as well as 30-day and five-year outcomes in patients with and without Takotsubo effect. Results Patients with Takotsubo effect showed significantly worse average peak systolic longitudinal strain (–9.5 ± 2.6% vs –11.1 ± 3.6%, p = 0.038), left ventricular ejection fraction (38.5 ± 6.8% vs 47.7 ± 8.7%, p = 0.000) and myocardial performance index (0.54 ± 0.17 vs 0.37 ± 0.15, p = 0.000) within 48 h of myocardial infarction. There was no significant difference between the two groups in diastolic ventricular filling pressures, hemodynamic consequences, and 30-day rehospitalization and mortality (Gehan-Breslow-Wilcoxon test: p = 0.157). However, patients with Takotsubo effect developed more major adverse cardiac events (log-rank test: p = 0.019) when tested at the five-year follow-up. Cox regression analysis revealed that age, hypotension, tricuspid annular plane systolic excursion, and Takotsubo effect were independent prediction factors for five-year major adverse cardiac events. The Doppler/tissue Doppler parameter E/e’ correlated with MACE only in patients without Takotsubo effect. Conclusion Takotsubo effect secondary to anterior ST-segment elevation myocardial infarction predicts a worse long-term prognosis.

OBJECTIVE To introduce a modified sequential vascular control strategy, mimicking the open 'milking' technique principle, for the early release of the first porta hepatis (FPH) and to stop cardiopulmonary bypass (CPB) in level III-IV robot-assisted inferior vena cava (IVC) thrombectomy (RA-IVCTE). PATIENTS AND METHODS From November 2014 to June 2019, 27 patients with a level III-IV IVC tumour thrombus (IVCTT) underwent RA-IVCTE in our department. The modified sequential control strategy was used in 12 cases. Previously, we released the FPH after the thrombus was resected and the IVC was closed completely, and CPB was stopped at the end of surgery (15 patients). Presently, using our modified strategy, we place another tourniquet inferior to the second porta hepatis (SPH) once the proximal thrombus is removed from the IVC below the SPH. Then, we suture the right atrium and perform early release of the FPH, and stop CPB. Finally, tumour thrombectomy, vascular reconstruction, and radical nephrectomy are performed. RESULTS Compared with the previous strategy, the modified steps resulted in a shorter median FPH clamping (19 vs 47 min, P

Introduction:Sexual activity is often an important component of life. To date, no studies have examined sexual activity before and after total hip arthroplasty (THA) in male patients with ankylosing spondylitis (AS). The purpose of the current study was to evaluate the effect of THA on sexual activity and to explore the most commonly reported and comfortable coital position for male AS patients with hip involvement.Methods:Data from 31 male AS patients who underwent THA for hip involvement were retrospectively reviewed. Information from the International Index of Erectile Function (IIEF), the Harris Hip Score (HHS) and other clinical parameters was collected and monitored over time. We compared the above-mentioned parameters before surgery and 2 years after surgery and analysed the correlation between changes on the IIEF and changes in clinical parameters.Results:The domain and total scores of the IIEF, except EF, were significantly higher after surgery than were those before surgery ( p < 0.05). There was a significant positive correlation between changes on the IIEF and improvement in flexion-extension range of motion (ROM), adduction-abduction ROM and HHS ( p < 0.05). Most patients (26/31, 83.9%) resumed sexual activity 5–12 weeks after surgery. The pre- and postoperative distributions of the most commonly reported and comfortable position were not significantly different (p > 0.05).Conclusions:Successful THA may improve sexual activity in male AS patients with hip involvement. Changes in hip ROM show the most significant correlation with improvement in sexual activity. Resumption of sexual activity occurs within 5–12 postoperative weeks.

Multiple sclerosis (MS) is an autoimmune disease characterized by T cell infiltration and demyelination of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a classical preclinical animal model of MS. In this study, we found that rotating magnetic field (RMF) treatment exerts potential preventive effects on the discovery of EAE, including reducing the severity of the disease and delaying the onset of the disease. The results indicated that RMF (0.2 T, 4 Hz) treatment increases the accumulation of CD4+ cells in the spleen and lymph nodes by downregulating the expression of CCL-2, CCL-3 and CCL-5, but has no significant effect on myelin oligodendrocyte glycoprotein (MOG) specific T cell responses. Simultaneously, RMF treatment adjusted the imbalance between regulatory T (Treg) cell and T helper 1 (Th1) cells or T helper 17 (Th17) cells by increasing the proportion of Treg cells and inhibiting the ratio of Th1 and Th17 cell subsets. These findings suggest that exposure to RMF may improve EAE disease by promoting CD4+ cell accumulation into peripheral lymphoid tissue, improving the imbalance between Treg and Th1/Th17 cells. Therefore, as a mild physical therapy approach, RMF, is likely to be a potential way to alter the development of EAE.

Background Deep knee infection (DKI), consisting of sepsis arthritis (SA) and chronic low-grade infection (CLGI), is a rare but catastrophic adverse event that can result from intra-articular (IA) injections. The purpose of this study was to assess the risk factors for DKI and describe the clinical characteristics of DKI in patients who received IA injections. Methods Fifty patients with IA injection-induced DKI who underwent surgical treatment between January 2010 and May 2016 served as cases and were matched with non-infected controls who received IA injections in a proportion of 1:5 based on age, gender, and date of admission. All IA injections (both cases and controls) were performed within 6 months of admission at our institution or at a referring institution. Risk factors for injection-induced DKI were analyzed, and the clinical characteristics between SA and CLGI were compared. Results The final multivariate logistic regression analysis demonstrated that body mass index ≥25kg/m 2 [odds ratio (OR) = 2.3; 95% confidence interval (CI): 1.1–4.7], corticosteroid injections (OR = 3.21; 95% CI: 1.63–6.31), rheumatoid arthritis (OR = 2.61; 95% CI: 1.20–5.68) and injections performed by general practitioners (OR = 5.23; 95% CI: 2.00–13.67) increased the risk of DKI following IA injections. Of 50 cases, there were 21 SA cases and 29 CLGI cases. SA cases had significantly higher metrics in the categories of fever, local warmth, swelling, rest pain, night pain, limited motion, serum WBC, and CRP levels than CLGI cases. Conclusions We identified risk factors and clinical characteristics of injection-induced DKI, which may offer improved guidance on IA injections and knowledge of DKI in patients with IA injections, especially in CLGI patients.

Limited research examines family planning for HIV-infected women with a history of injection drug use. We describe modern contraceptive use and its association with heavy drinking and recent injection for HIV-infected females in St. Petersburg, Russia (N = 49): 22.4% (n = 11) used traditional methods and 30.6% (n = 15) reported modern contraceptive use, which consisted primarily of condoms (26.5%, n = 13). Over 63% (n = 31) had an abortion. Observed associations for heavy alcohol use (AOR = 2.36, CI = 0.53, 12.41) and recent injection drug use (AOR = 2.88, CI = 0.60, 16.92) were clinically notable, but not statistically significant. Prioritizing family planning for HIV-infected women with a history of substance use is urgently needed.

Although overall downregulation of microRNAs (miRNAs) is a general feature of clear-cell renal cell carcinoma (ccRCC), several miRNAs are consistently upregulated, among which miR-122 was markedly increased in ccRCC tissues. Our study aims to determine the functional importance and underlying mechanism of miR-122 in ccRCC metastasis. Here, we demonstrate that the expression of miR-122 increased in ccRCC tissues, and higher miR-122 expression was found in ccRCC tissues with metastatic disease than in those without metastasis. The increased miR-122 levels were associated with poor metastasis-free survival in ccRCC patients with localized disease. Dicer was validated as a direct functional target of miR-122. Overexpression of miR-122 promoted migration and invasion of ccRCC cells in vitro and metastatic behavior of ccRCC cells in vivo. Inhibition of miR-122 attenuated this metastatic phenotype in vitro. Importantly, miR-122 exerted its pro-metastatic properties in ccRCC cells by downregulating Dicer and its downstream effector, the miR-200 family, thereby inducing epithelial-mesenchymal transition (EMT). Our results suggest an important role of the miR-122/Dicer/miR-200s/EMT pathway in ccRCC metastasis. Furthermore, miR-122 may serve as a biomarker for discriminating ccRCC with metastatic potential.

Introduction: Although the contribution of mosaicism to tumorigenesis emerges during embryonic development, it is a very rare phenomenon in tumor patients. Only a few mosaic RAS mutations have been identified, such as NRAS G12D, NRAS G12S, KRAS G12D. They have been proved to affect the progression of cutaneous tumors and hematologic tumors. Here, we provide the first evidence that mosaic KRAS G12S mutation, a new locus, could significantly promote progression of tumor, papillary thyroid carcinoma. Case presentation: We report a 58-years-old woman, whose right thyroid neoplasms were diagnosed as papillary thyroid carcinoma five years ago. She had a recurrence accompanied by metastases involving the larynx, hypopharynx, esophagus, internal jugular vein, and bilateral lymph node. The tumor showed no response to sorafenib. Biopsy sample of the recurrence tumor was subjected to targeted next generation sequencing (NGS). The results showed BRAF V600E mutation and TERT promoter mutation of chr5: 1,295,228C>T (C228T) in the tumor sample. Meanwhile, we found KRAS G12S mutations in the tumor sample and normal control tissue. Further examination of the blood cells, plasma, urine and saliva of the patient, all showed KRAS G12S mutations, thus, the patient had mosaic KRAS G12S mutation. Given the patient's tumor had mutation of BRAF V600E, she then received combination therapy with dabrafenib, 150 mg twice daily, and trametinib, 2 mg daily. After 5 months of dabrafenib and trametinib treatment, the tumor was significantly reduced. After that, the disease progressed rapidly, and transformed to anaplastic carcinoma. Targeted NGS results of biopsy sample at this time showed that BRAF V600E mutation and TERT promoter mutation of C228T were remained, and the patient died quickly. Discussion: Somatic mutations of BRAF V600E and KRAS are mutually exclusive, because both are on the same RAS/RAF/MEK/ERK pathway. Rare patients had co-mutations of them. Only one report about a BRAF V600E PTC patient had an acquired KRAS G12V after the treatment of dabrafenib and trametinib and proved the KRAS G12V was one resistant mechanism of this strategy. Here, this was the first evidence that the mosaic KRAS G12S mutation, but not acquired mutation, resulted in a poorer prognosis of BRAF mutant PTC patient with dabrafenib and trametinib treatment: only 5 months of response in this patient, while 12.6 months of median duration of response in BRF113928 clinical trial of this combo strategy. Conclusion: This was the first report that mosaic KRAS G12S mutation was associated with cancer, and it was also the first report of mosaicism in thyroid tumor. We speculated that mosaic KRAS G12S mutation was one of the factors leading to more malignant tumor and rapid disease progression. These results suggest that it is important to pay attention to mosaic mutations when detecting the somatic mutations of tumor. Citation Format: Sheng Yang, Xin Zhang, Xiaoyan Zhang, Kan Liu, Tonghui Ma, Chengyun Geng, Yanling Niu, Xiaohui He. Mosaic KRAS G12S mutation associates with poor outcome in papillary thyroid carcinoma: A case report [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1199.

Objectives To assess the impact of the presence of bland thrombus (BT) on prognosis of patients treated with resection of renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVCTT). Materials and methods The medical records of a total of 145 consecutive postsurgical RCC patients with level I-IV IVCTT were reviewed from January 2008 to August 2018. Associations of BT with clinicopathological variables were estimated by chi-square test or Student's t-test. Kaplan-Meier method and multivariate Cox proportional hazard model were used. The eighth TNM staging system, “Spiess PE” model, University of California at Los Angeles Integrated Staging System and Stage, Size, Grade, and Necrosis (SSIGN) score were selected to assess whether BT could improve their predictive abilities. Results BT was observed in 34 (23.4%) patients and was significantly associated with increased levels of IVCTT (P = 0.004) and invasion of IVC wall (P = 0.030). Multivariable Cox analyses revealed that tumor grade, T stage, M stage, tumor thrombus consistency and BT were independent risk factors for both progression-free survival and overall survival. The concordance indexes ranged from a low of 0.652 in TNM to a high of 0.731 in SSIGN, and integrating BT into each base model led to an increased predictive accuracies of 6.2% for TNM (P = 0.025), 4.0% for “Spiess PE” model (P = 0.069), 2.1% for University of California at Los Angeles Integrated Staging System (P = 0.149) and 1.2% for SSIGN (P = 0.290), respectively. Conclusions Presence of BT was independently associated with survival in postsurgical patients with RCC-IVCTT. Routine consideration of BT as an adjunct to TNM staging system may be suggested.

Human tumor cell lines, especially those with complete data and follow-up, are important tools in tumor biological studies. Clear cell renal cell cancer (ccRCC) is not sensitive to radiotherapy or chemotherapy, and treatment of patients with distant metastasis relies on targeted therapy. Here, we report the establishment of seven new ccRCC stable cell lines that were continuously cultured for more than 20 generations among 81 cases of renal cell cancer. Moreover, gene expression and methylation in the established cell lines, in those that had a finite in vitro life span of less than 10 generations, and in cells that originated from the same culture at different generations were profiled using microarrays. Genes including SLC34A2, SEPP1, SULT1C4 and others were differentially expressed in established cell lines and finite cell lines, and changes in their expression might be caused by methylation or demethylation. The expression level of SLC34A2 was related not only to the life span in vitro culture but also to tumor size. Additionally, six of the seven new ccRCC cell lines had VHL deletions or termination mutations. So in addition to the establishment of seven new ccRCC cell lines with complete clinical data, we conclude that genes such as SLC34A2 and VHL play key roles in the continuous in vitro growth and development of ccRCC.

The transcription factor KLF6 has an essential role in the development and metastasis of multiple human cancers. Paradoxically, KLF6 expression was found to be attenuated in primary metastatic clear cell renal cell carcinoma (ccRCC), such that it is unclear how KLF6 affects malignant progression in this setting. In this study, we demonstrate that KLF6 attenuation in renal cells is sufficient to promote E2F1-mediated epithelial–mesenchymal transition and metastatic prowess. In a mouse xenograft model of human ccRCC, silencing KLF6 increased tumor cell proliferation and malignant character, whereas E2F1 silencing reversed these properties. These effects were corroborated in a metastatic model system, where we observed a greater number of pulmonary metastatic lesions formed by ccRCC cells where KLF6 was silenced and E2F1 enforced. Analysis of clinical specimens of ccRCC revealed that low levels of KLF6 and high levels of E2F1 correlated closely with ccRCC development. Overall, our results established the significance of activating the KLF6–E2F1 axis in aggressive ccRCC, defining a novel critical signaling mechanism that drives human ccRCC invasion and metastasis. Cancer Res; 77(2); 330–42. ©2016 AACR.

Hyperoxic acute lung injury (HALI) is caused by prolonged exposure to high oxygen partial pressure. This study was undertaken to investigate the protective effects of oridonin on HALI in a mouse model. Mice were randomly divided into three groups: the control group, HALI group and oridonin (ORI) group. HALI was induced by exposing mice to pure oxygen at 2.5 atmospheres absolute (ATA) for six hours in the HALI and ORI groups. In the ORI group, mice were intraperitoneally injected with ORI at 10 mg/kg twice daily after hyperoxic exposure. Animals were sacrificed 24 hours after the hyperoxia exposure, followed by bronchoalveolar lavage fluid (BALF). Lungs were then collected. Each lung was processed for HE staining and detection of wet-to-dry weight ratio. The lactate dehydrogenase (LDH) activity and protein content of BALF were determined, and the contents of malonaldehyde (MDA), glutathione (GSH), tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) in the lung were measured. Our results showed prolonged exposure to hyperoxia significantly damaged the lung, caused lung edema, increased MDA and TNF-α, and reduced GSH and IL-10 in the lung. However, post-exposure treatment with oridonin was able to improve lung pathology, attenuate lung edema, reduce MDA and TNF-α, and increase GSH and IL-10 in the lung. These findings suggest that oridonin can protect the lung against hyperoxia-induced injury in mice.

BACKGROUND The poor prognosis of cardiac sarcoidosis (CS) underscores the need for risk stratification. PURPOSE To investigate the prognostic significance of ventricular/myocardial remodeling features in sarcoidosis. STUDY TYPE Retrospective. POPULATION In all, 132 biopsy-proven sarcoidosis patients imaged from 2008 to 2018. The primary endpoint was a composite of cardiac mortality, new onset arrhythmias, hospitalization for heart failure, and device implantation. FIELD STRENGTH/SEQUENCE No field strength or sequence restrictions. ASSESSMENT Global and regional ventricular/myocardial remodeling features were assessed by standard volumetric measurements and automated function imaging postprocessing analysis. STATISTICAL TESTS Student's t-test or Mann-Whitney test (chi2 test or Fisher's exact test for categorical variables) were used for comparisons. Cox-proportional hazards regression model, univariate /multivariate analyses, and receiver operating characteristic were performed to relate clinical/lab data, imaging parameters to the endpoints. RESULTS Over a median follow-up of 40.7 (interquartile range 18.8-60.5) months, 41 (31.1%) patients developed adverse cardiac events. Abnormal left ventricular (LV) geometric remodeling alterations (measured by LV mass index and relative wall thickness) occurred 3.66-fold more frequently in patients with endpoints than patients without. The ratio of patients with endpoints increased as ventricular remodeling phenotype progressed. In patients with endpoints, regional myocardial wall thickness (RMWT) was significantly (P = 0.022) increased in six clustered LV segments located in the middle interventricular septum and basal/middle anterolateral walls. In all of the abnormal ventricular remodeling stages, patients with endpoints constantly had higher mean RMWT than those without. Among clinical, electrocardiographic, and imaging parameters, LV mass index (hazard ratio [HR] 1.010 95% confidence interval [CI] 1.002-1.018, P = 0.017) and mean RMWT (HR 3.482 95% CI 1.679-7.223, P = 0.001) were independently associated with endpoints. Sarcoidosis patients without this RMWT distribution pattern were significantly (P

BACKGROUND Mayo adhesive probability (MAP) score, an accurate and reliable predictor of adherent perinephric fat (APF), consists of posterior perinephric fat thickness and perinephric fat stranding. The present study aimed to identify the potential clinical characteristics associated with these 2 variables to further our understanding of APF. MATERIAL AND METHODS Clinical data of 346 patients subjected to minimally invasive nephrectomy was collected within our prospectively maintained database, between January 2015 and December 2016. Radiological data was assessed by 2 readers in an independent blinded - to each other and APF patient status - fashion. Ordinal logistic regression analyses were performed to evaluate risk factors of posterior perinephric fat thickness and perinephric fat stranding. RESULTS On multivariate analysis, posterior perinephric fat thickness was associated with older age (s=1.05 [range, 1.03-1.07], P

Objective: The aim of this study was to explore a new treatment strategy for left renal vein tumor thrombus directed at the thrombus level and the therapeutic effect of robotic surgery. Ma...

Background Level III-IV robot-assisted inferior vena cava (IVC) thrombectomy (RA-IVCT) has been reported in limited series. Objective To report our initial series of level III-IV RA-IVCT with step-by-step procedures and 1-yr outcomes. Design, setting, and participants From November 2014 to January 2018, 13 patients with level III-IV IVC tumor thrombi underwent RA-IVCT with a minimum of 1-yr follow-up. Surgical procedure Level III RA-IVCT requires liver mobilization and clamping of first porta hepatis (FPH), and suprahepatic and infradiaphragmatic IVC. Level IV RA-IVCT requires establishment of cardiopulmonary bypass (CPB). Thoracoscopy-assisted thrombectomy was performed for the intra-atrium part of the thrombus under CPB. Infradiaphragmatic RA-IVCT was completed in a manner similar to that of level III RA-IVCT. Measurements Detailed techniques were described for various scenarios. Baseline and perioperative outcomes were reported, and descriptive statistical analysis was performed. Results and limitations Median operative time was 465 (interquartile range [IQR]: 338–567) min. Median estimated intraoperative blood loss was 2000 (IQR: 1000–3000) ml. The rates of intraoperative blood transfusion and postoperative transformation to the intensive care unit ward were 92.3% and 100%, respectively. Median FPH blocking time was 40 (IQR: 25–60) min and the CPB time was 72 (IQR: 51–87) min. Three cases had grade IV complications, including two vascular injuries that were treated with intraoperative endoscopic sutures and one perioperative death. The perioperative mortality rate was 7.7%. During an 18-mo follow-up, two patients died and one patient progressed. Conclusions Although the risks involved are high, level III-IV RA-IVCT is feasible and serves as an alternative minimally invasive method for selected patients. It also requires more complex techniques and multidisciplinary cooperation. Patient summary We studied the treatment of patients with level III-IV inferior vena cava (IVC) tumor thrombi using a robotic approach. This technique was feasible for well-selected patients. However, level III-IV robot-assisted IVC thrombectomy requires more complex techniques and multidisciplinary cooperation.

Up to one-third of patients selected by current guidelines do not respond to cardiac resynchronization therapy (CRT), the aim of this study was to find out novel analytical approaches to improve pre-implantation CRT response prediction. Among 31 pre-implantation features of clinical, laboratory, electrocardiography (ECG), and echocardiography variables in a consecutive cohort of patients receiving a first-time CRT device (CRT-pacemaker or CRT-defibrillator), we developed a machine learning (ML) model with three classification algorithms (support vector machines (SVM), K nearest neighbors, and random subspaces) with the best features combination to predict CRT response. Three categorical variables, left bundle branch block (LBBB), nonischemic cardiomyopathy, and female gender, were independently associated with CRT responses. Among continuous variables, including septal wall thickness, posterior wall thickness, and relative wall thickness (RWT), could regularize ECG QRS duration (QRSd) and significantly enhance the correlation between QRSd and CRT response. The 3 ML algorithms in a total of 38 features combinations constantly recognized that the features combined with QRSd/RWT outperformed the combinations without it. For each of three algorithms, the triplet feature combination of QRSd/RWT, LBBB, and nonischemic cardiomyopathy repeatedly increased the classification rate more than 8%. The best performance for CRT response prediction occurred with SVM model, which proposed actual QRSd/RWT values that favored CRT responses in patients both with and without LBBB. Lower QRSd/RWT values were required for CRT responses in patients with ischemic cardiomyopathy compared to those with non-ischemic cardiomyopathy. ML from ventricular remodeling characteristics-regularized QRSd improves CRT response prediction.

Common causes of complications of laparoscopic pyeloplasty in children include anastomotic stricture, poor drainage due to high ureteropelvic anastomosis, and torsion of ureter. Herewith, we described our modified technique of paraumbilical three-port laparoscopic dismembered pyeloplasty (PTLDP) to minimize these complications. Data from 62 patients (age: 1–180 months, median: 12 months) with ureteropelvic junction obstruction (UPJO) who underwent pyeloplasty using our modified technique of PTLDP between February 2014 and September 2014 at our institution were reviewed. The key steps of our modified method involve identifying the lowest point of the renal pelvis and the lateral aspect of the ureter to guarantee a low pelviureteric and correct orientation anastomosis, and using a 4-0 silk for assistant suturing to avoid crushing of the anastomotic tissue. All surgeries were successfully completed without conversion. Three patients required an accessory port for the anastomosis. All the patients achieved complete clinical or radiologic resolution after the operation. The mean operative time was 103.4 min, and mean estimated blood loss was 14.4 mL. Mean postoperative differential function of affected kidney was 43.0 ± 16.3 % (range 24–100 %), increased from 39.7 ± 18.0 % (range 18–100 %), preoperatively (p

Background The safety and feasibility of robot-assisted laparoscopic inferior vena cava (IVC) thrombectomy (RAL-IVCTE) have been investigated in limited reports. Objective To share our initial experience with RAL-IVCTE, as well as describe respectively the detailed techniques for RAL-IVCTE for left or right renal cell carcinoma (RCC). Design, setting, and participants From May 2013 to July 2014, 17 patients with RCC involving IVC tumor thrombus were admitted to our hospital. Surgical procedure For right RCC, the caudal IVC, left renal vein, and cephalic IVC were sequentially clamped. The IVC wall was cut, and the thrombus was removed. For left RCC, the left renal vein, which included the thrombus, was ligated with Endo-GIA. The caudal IVC, right renal artery, right renal vein, and cephalic IVC were sequentially clamped. Measurements The detailed techniques for RAL-IVCTE for different sides were described and the perioperative outcomes recorded. Results and limitations The operations were successfully performed without open conversion. Median operation time was 131min (100–150min) and 250min (190–275min) for the right and left RCC, respectively. Median estimated blood loss was 240ml (145–320ml). Median IVC blocking time was 17min (12–25min). For left RCC, median warm ischemia time for the right kidney was 18min (14–22min). A grade IV complication—bleeding from tributaries of the IVC—developed in one case and was successfully resolved with intraoperative endoscopic suture. Conclusions RAL-IVCTE is safe and feasible. For left RCC involving IVC thrombus, right renal warm ischemia time is necessary during the procedure, requiring a more advanced technical skill. The therapeutic effect and overall survival rate require further investigation with a larger sample size and longer follow-up. Patient summary Robot-assisted laparoscopic inferior vena cava thrombectomy is technically challenging but safe and feasible. The therapeutic effect needs further investigation.

// Yang Fan 1, * , Hongzhao Li 1, * , Xin Ma 1 , Yu Gao 1 , Xu Bao 2 , Qingshan Du 1 , Minghui Ma 1 , Kan Liu 1 , Yuanxin Yao 1 , Qingbo Huang 1 , Yu Zhang 1 , Xu Zhang 1 1 Department of Urology, State Key Laboratory of Kidney Diseases, Chinese People’s Liberation Army General Hospital, PLA Medical School, Beijing, People’s Republic of China 2 Medical School, Nankai University, Tianjin, People’s Republic of China * These authors contributed equally to this work Correspondence to: Xu Zhang, e-mail: xzhang@foxmail.com Keywords: clear cell renal cell carcinoma, von Hippel–Lindau, hypoxia-inducible factor, dicer, microRNA Received: September 08, 2015 Accepted: January 23, 2016 Published: March 01, 2016 ABSTRACT Both the von Hippel-Lindau (VHL)/hypoxia-inducible factor (HIF) pathway and microRNA (miRNA) regulation are important mechanisms underlying the development and progression of clear cell renal cell carcinoma (ccRCC). Here we demonstrate that VHL deficiency leads to downregulation of Dicer and, in turn, defects in the miRNA biogenesis machinery in ccRCCs. Dicer inhibited expression of HIF-2α, which was a direct target of Dicer-dependent miR-182-5p in VHL-deficient ccRCCs. Ectopic Dicer expression in VHL-deficient ccRCCs suppressed tumor growth and angiogenesis by inhibiting HIF-2α both in vitro and in vivo . Reduced Dicer mRNA levels served as an independent prognostic factor for poor survival in patients with VHL-deficient ccRCC. Our results indicate that downregulation of Dicer in VHL-deficient ccRCCs contributes to high levels of HIF-2α and a malignant phenotype, which suggests Dicer could be a useful therapeutic target for managing this disease.