Underlying mechanisms of saphenous vein graft stenosis after coronary artery bypass caused by clipping of the side branches: an experimental study

BackgroundSaphenous veins are regular bypass conduits selected in non-left anterior descending artery (LAD) coronary artery bypass graft (CABG) surgery. Despite the technical errors, acute thrombosis, intimal hyperplasia and arteriosclerosis which could lead to saphenous vein graft (SVG) failure, the metal-clipping-related SVG failure is unique and rare. This study was conducted to investigate the clinical and underlying mechanisms of the metal-clipping-related SVG failure.MethodsWe collected 6 typical cases of the metal-clipping-related SVG failure in 41 patients who were diagnosed graft stenosis by coronary angiograph after CABG in the Department of Cardiology, Beijing Anzhen Hospital, from January 2020 to September 2021. Furthermore, we built an in vitro model to verify the identical intravascular ultrasound (IVUS) pattern of metal clip.ResultsThere were 6 in 41 cases of SVG stenosis caused by clipping of the side branches. We found that the stenosis of SVG caused by metal clipping mostly occurred at the corner and multipole clipping points. In this situation, great resistance could be felt when pushing the instruments through the stenosis and crystallized cholesterol was rarely caught by the distal protection device. We verified the similar IVUS pattern of metal clip at the side-branches of SVG in vitro.ConclusionsThe metal-clipping-related stenosis may lead to SVG failure. The stenosis of SVG caused by metal clipping mostly occurred at the corner and multipole clipping points. IVUS showed great modality for clarification.     

Sarcopenia with systemic inflammation can predict survival in patients with hepatocellular carcinoma undergoing curative resection

BackgroundThis study aimed to examine the prognostic significance of sarcopenia combined with systemic inflammation in patients who underwent curative hepatectomy for hepatocellular carcinoma (HCC).MethodsBetween January 2010 and July 2019, we identified 159 patients with HCC who underwent curative hepatectomy at three institutional centers. We retrospectively analyzed clinicopathological outcomes, surgical outcomes, platelet lymphocyte ratio (PLR) as a systemic inflammatory marker, and computed tomography (CT)-assessed sarcopenia at the third lumbar vertebra level (L3).ResultsSarcopenia was noted in 74 (46.5%) of 159 patients and was significantly associated with male sex, low body mass index (BMI), and high PLR. In the multivariate analysis, sarcopenia [hazard ratio (HR): 2.127, P=0.026] and high PLR (HR: 1.971, P=0.038) were associated with a decrease in overall survival (OS) but not in recurrence-free survival (RFS). The combination of sarcopenia and PLR status stratified the 5-year OS into 82.0% (non-sarcopenia and a low PLR), 68.3% (sarcopenia or a high PLR), and 44.4% (sarcopenia and a high PLR) (P=0.001). In the multivariate analysis, “sarcopenia and a high PLR” and “sarcopenia or a high PLR” were revealed to be significant predictors of OS (HR: 4.300, P=0.001 and HR: 2.723, P=0.010, respectively).ConclusionsSarcopenia and high PLR were significantly associated with poor OS. The combination of these two factors may be useful for predicting survival of patients with HCC undergoing curative hepatectomy.     

Toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a single-center,single-arm clinical trial (ESONICT-2)

BackgroundMore and more evidence has confirmed the efficacy and safety of immunotherapy drugs, such as camrelizumab and pembrolizumab. There are several phase-I/II studies showing that toripalimab has an acceptable safety profile and promising clinical activity in patients with advanced solid tumors. To further confirm its efficacy and safety, the aim of the study was to evaluate toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC).MethodsThis study was an investigator-initiated, open-label, non-randomized, single-arm, single-center phase II trial (registration number: ChiCTR2100052784). The patients eligible for inclusion criteria at Fujian Medical University Union Hospital from October 2019 to October 2020 were included in this study. Patients who were suitable for surgery underwent minimally invasive esophagectomy (MIE) within 4–6 weeks after neoadjuvant therapy. Pathological complete response (pCR) and adverse events (AEs) were the primary end points. Secondary endpoints included R0 resection rate, major pathological response (MPR), interval to surgery, and 30-day complications.ResultsA total of 20 patients were enrolled from October 2019 to October 2020. All patients successfully completed 2 cycles of neoadjuvant therapy. Treatment-related AEs were common during neoadjuvant therapy, with leucopenia the most frequently occurring AE (4/20, 25%). With respect to immune-related AEs, immune dermatitis occurred in 2 patients, including 1 patient with grade I and 1 patient with grade III. Based on radiologic evaluation, the objective response rate (ORR) was 70% (14/20). Twelve patients underwent McKeown MIE. The pCR rate of the primary tumor was 16.7% (2/12), and the MPR rate of the primary tumor was 5/12 (41.7%). The mean interval to surgery was 33.2 days, and no patients experienced delayed surgery due to treatment-related AEs. Pneumonia was the most common 30-day postoperative complication (3/12, 25%). Anastomotic leakage (AL) only occurred in 1 patient during the hospital stay. There were no treatment- or surgery-related deaths.ConclusionsBased on our results, toripalimab combined with docetaxel and cisplatin as a novel neoadjuvant therapy was safe and effective in locally advanced ESCC.     

重症慢阻肺患者短期营养支持下血清游离脂肪酸的变化

对25例重症慢性阻塞性肺疾病(COPD)伴营养不良的患者进行初步营养评价,并对其中12例给予口服加静脉营养支持治疗,观察患者在短期营养支持下血清游离脂肪酸(FFA)的变化。结果表明,短期营养支持并不能显著改善 FFA 水平(P<0.01),但在一定程度上增加患者体重,提高血清蛋白水平,脂肪乳剂的应用,可降低此类患者的动脉二氧化碳分压(PaCO_2),对 COPD 患者显示初步疗效。     

早期激素性股骨头缺血性坏死的实验研究

取成年健康英国罗斯鸡１５只，随机分为２组，Ｂ组为对照组，Ａ组注射大剂量甲基氢化泼尼松。结果显示，Ａ组鸡股骨头软骨下骨髓造血细胞减少，脂肪细胞肥大，骨髓水肿及空骨陷窝明显增多。对照组股骨头未见异常，提示股骨头坏死由缺血所致。     

Changes in imatinib plasma trough level during long-term treatment of patients with advanced gastrointestinal stromal tumors: correlation between changes in covariates and imatinib exposure

A pharmacokinetic study in patients with gastrointestinal stromal tumors (GIST) suggested that imatinib plasma concentration may decrease following long-term exposure. We assessed changes in imatinib plasma trough levels (C(min)) during long-term treatment. Follow-up (FU) imatinib C(min) was measured in 65 patients who received the same dose of imatinib for at least 9 months after previous (initial) tests. After exclusion of 7 patients who had been treated with imatinib for over 2 years at the time of initial testing, 58 patients were included in this analysis. The median intervals from initiation of imatinib to initial testing and from initial to FU testing were 5.5 months (range, 0.5-24.0 months) and 13.0 months (range, 9.6-17.9 months), respectively. Mean inter- and intra-subject variability values were 47.7% and 20.9%, respectively, at initial measurements, and 45.2% and 19.4%, respectively, at FU. Mean FU imatinib C(min) (1,370 ± 661 ng/mL) was significantly higher than mean initial C(min) (1,171 ± 573 ng/mL; p = 0.003). Compared with initial C(min), FU C(min) was decreased in 22 patients and increased in 36, with median changes of 13% and 32%, respectively. Multivariate analysis showed a significant correlation between the ratio of FU to initial imatinib C(min) and that of albumin (r = -0.39, p = 0.003). During long-term treatment, imatinib C(min) did not decrease significantly but remained stable or increased in most patients. Changes in imatinib C(min) were associated with changes in albumin concentration. Monitoring of imatinib C(min) only for concerns about time-dependent increases in imatinib clearance is not necessary.     

Cell Death by Polyvinylpyrrolidine-Coated Silver Nanoparticles is Mediated by ROS-Dependent Signaling

Silver nanoparticles (AgNPs) are widely used nanoparticles and they are mainly used in antibacterial and personal care products. In this study, we evaluated the effect of AgNPs on cell death induction in the murine dendritic cell line DC2.4. DC2.4 cells exposed to AgNPs showed a marked decrease in cell viability and an induction of lactate dehydrogenase (LDH) leakage in a time- and dose-dependent manner. In addition, AgNPs promoted reactive oxygen species (ROS)-dependent apoptosis and AgNP-induced ROS triggered a decrease in mitochondrial membrane potential. The activation of the intracellular signal transduction pathway was also observed in cells cultured with AgNPs. Taken together, our data demonstrate that AgNPs are able to induce a cytotoxic effect in DCs through ROS generation. This study provides important information about the safety of AgNPs that may help in guiding the development of nanotechnology applications.     

Imaging-Based Tumor Treatment Response Evaluation: Review of Conventional, New, and Emerging Concepts

Tumor response may be assessed readily by the use of Response Evaluation Criteria in Solid Tumor version 1.1. However, the criteria mainly depend on tumor size changes. These criteria do not reflect other morphologic (tumor necrosis, hemorrhage, and cavitation), functional, or metabolic changes that may occur with targeted chemotherapy or even with conventional chemotherapy. The state-of-the-art multidetector CT is still playing an important role, by showing high-quality, high-resolution images that are appropriate enough to measure tumor size and its changes. Additional imaging biomarker devices such as dual energy CT, positron emission tomography, MRI including diffusion-weighted MRI shall be more frequently used for tumor response evaluation, because they provide detailed anatomic, and functional or metabolic change information during tumor treatment, particularly during targeted chemotherapy. This review elucidates morphologic and functional or metabolic approaches, and new concepts in the evaluation of tumor response in the era of personalized medicine (targeted chemotherapy).