Predictive model for totally implanted venous access ports­related long­term complications in patients with lung cancer.

Totally implanted venous access ports (TIVAPs), which are typically used in oncological chemotherapy and parenteral nutritional support, are convenient and safe, and thus offer patients a higher quality of life. However, insertion or removal of the device requires a minor surgical operation. Long-term complications (>30 days post insertion), such as catheter migration, catheter-related thrombosis and infection, are major reasons for TIVAP removal and are associated with a number of factors such as body mass index and hemoglobin count. Since management of complications is typically time-consuming and costly, a predictive model of such events may be of great value. Therefore, in the present study, a predictive model for long-term complications following TIVAP implantation in patients with lung cancer was developed. After excluding patients with a large amount of missing data, 902 patients admitted to The First Affiliated Hospital with Nanjing Medical University (Nanjing, China) were ultimately included in the present study. Of the included patients, 28 had complications, indicating an incidence rate of 3.1%. Patients were randomly divided into training and test cohorts (7:3), and three machine learning-based anomaly detection algorithms, namely, the Isolation Forest, one-class Support Vector Machines (one-class SVM) and Local Outlier Factor, were used to construct a model. The performance of the model was initially evaluated by the Matthew's correlation coefficient (MCC), area under curve (AUC) and accuracy. The one-class SVM model demonstrated the highest performance in classifying the risk of complications associated with the use of the intracavitary electrocardiogram method for TIVAP implantation in patients with lung cancer (MCC, 0.078; AUC, 0.62; accuracy, 66.0%). In conclusion, the predictive model developed in the present study may be used to improve the early detection of TIVAP-related complications in patients with lung cancer, which could lead to the conservation of medical resources and the promotion of medical advances.

Hypomethylation-enhanced CRTC2 expression drives malignant phenotypes and primary resistance to immunotherapy in hepatocellular carcinoma.

The cyclic AMP-responsive element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a crucial regulator of hepatic lipid metabolism and gluconeogenesis and correlates with tumorigenesis. However, the mechanism through which CRTC2 regulates hepatocellular carcinoma (HCC) progression is largely unknown. Here, we found that increased CRTC2 expression predicted advanced tumor grade and stage, as well as worse prognosis in patients with HCC. DNA promoter hypomethylation led to higher CRTC2 expression in HCC. Functionally, CRTC2 contributed to HCC malignant phenotypes through the activated Wnt/ß-catenin pathway, which could be abrogated by the small-molecular inhibitor XAV-939. Moreover, Crtc2 facilitated tumor growth while concurrently downregulating the PD-L1/PD-1 axis, resulting in primary resistance to immunotherapy. In immunocompetent mice models of HCC, targeting Crtc2 in combination with anti-PD-1 therapy prominently suppressed tumor growth by synergistically enhancing responsiveness to immunotherapy. Collectively, targeting CRTC2 might be a promising therapeutic strategy to sensitize immunotherapy in HCC.

Mutational landscape of paired primary and synchronous metastatic lymph node in chemotherapy naive gallbladder cancer.

BACKGROUND: Comprehensive genomic analysis of paired primary tumors and their metastatic lesions may provide new insights into the biology of metastatic processes and therefore guide the development of novel strategies for intervention. To date, our knowledge of the genetic divergence and phylogenetic relationships in gallbladder cancer (GBC) is limited. METHODS: We performed whole exome sequencing for 5 patients with primary tumor, metastatic lymph node (LNM) and corresponding normal tissue. Mutations, mutation signatures and copy number variations were analyzed with state-of-art bioinformatics methods. Phylogenetic tree was also generated to infer metastatic pattern. RESULTS: Five driver mutations were detected in these patients. Among which, TP53 was the only shared mutation between primary tumor and LNM. Although tumor mutational burden was comparable between primary tumor and LNM, higher mutation burden was observed in LNM of one patient. Copy number variations (CNVs) burden was higher in LNM than their primary tumor. Phylogenetic analysis indicated both linear and parallel progression of metastasis exist in these patients. TP53 mutation and CNVs were homogenously between primary tumor and LNM. CONCLUSIONS: High consistence of genetic landscape were shown between primary tumor and LNM in GBC. However, heterogenicity still exist between primary tumor and LNM in particular patients in term of driver mutation, TMB and CNV burden. Phylogenetic analysis indicated both Linear and parallel progression of metastasis were exist among these patients.

Hsa_circ_0001361 facilitates the progress of lung adenocarcinoma cells via targeting miR-525-5p/VMA21 axis.

BACKGROUND: Lung adenocarcinoma (LUAD) is a common subtype of lung cancer with high recurrence rate and fatality. Circ_0001361 has been recognized as key regulators in various malignancies, but its roles in LUAD remain ambiguous. METHODS: Circ_0001361, miR-525-5p, and VMA21 levels were assessed by RT-qPCR. The growth and metastasis of LUAD cells were detected by MTT, colony formation, wound scratch, and transwell assays, respectively. The interaction between circ_0001361/VMA21 and miR-525-5p was detected by dual luciferase, RNA immunoprecipitation, and RNA pull-down assays. VMA21 protein level was detected by Western blotting. Nude mouse xenograft model was established to determine the role of circ_0001361 in tumor growth in vivo. RESULTS: Circ_0001361 was up-regulated, while miR-525-5p was down-regulated in LUAD tissues and cells. Functional experiments demonstrated that circ_0001361 drove LUAD cell growth and metastasis. Mechanistically, circ_0001361 functioned as a sponge of miR-525-5p to up-regulate downstream target VMA21 level. MiR-525-5p/VMA21 axis was involved in circ_0001361-mediated malignant phenotypes of LUAD cells. Finally, inhibition of circ_0001361 restrained in vivo xenograft tumor growth via regulating miR-525-5p/VMA21 axis. CONCLUSION: Our findings elucidate that circ_0001361 facilitates the tumorigenesis and development of LUAD through miR-525-5p/VMA21 axis, providing evidence for circ_0001361 as a potential prognosis biomarker and therapeutic target for clinical treatment of LUAD.

Comparison of thermal ablation and routine surgery for the treatment of papillary thyroid microcarcinoma: a systematic review and Meta-analysis.

BACKGROUND: Thermal ablation (TA), as an alternative to surgery, has shown some benefits in the treatment of papillary thyroid microcarcinoma (PTMC) patients, especially for those who are at high risk for surgery or refuse surgery. We performed a systematic review and meta-analysis to evaluate the efficiency, safety, and economy of TA, compared with those of routine surgery (RS), for the treatment of PTMC. METHODS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases were retrieved from inception to 10 January 2020 to identify relevant original studies on comparison of TA and RS for treatment of PTMC. The recurrence rate, recurrence-free survival (RFS), complication rate, operation time, postoperative length of stay, and cost during the perioperative period were extracted as main indices. The pooled standardized mean difference (SMD) or odds ratio (OR) with 95% confidence intervals (CI) were calculated and analyzed. Chi-square test and I2 statistic were applied to determine the heterogeneity among studies. The sensitivity analysis was applied to explore the origin of heterogeneity, and the publication bias was evaluated by Egger's test. RESULTS: Seven retrospective studies with a total of 867 patients met the eligibility criteria and were included in the final meta-analysis. Our study demonstrated that TA showed significant reduction in complication with a pooled OR 0.24 (95% CI 0.13 to 0.43), postoperative length of stay with a pooled SMD -3.14 (95% CI -4.77 to -1.51) and cost during the perioperative period with a pooled SMD of -1.69 (95% CI -3.18 to -0.20). It also demonstrated that both TA and RS had similar pooled proportion of recurrence of OR 0.93 (95% CI 0.38 to 2.30) and recurrence-free survive (RFS). The sensitivity analysis showed that each included study had no significant effect on the results and the results were stable and reliable. The Egger's test demonstrated publication bias was acceptable. CONCLUSIONS: TA may not be oncologically inferior to RS, and it is a relatively safe and economical alternative for the treatment of PTMC.

Comparison of microwave ablation treatments in patients with renal secondary and primary hyperparathyroidism.

Purpose: Microwave ablation (MWA) is feasible for severe renal secondary hyperparathyroidism (SHPT) and primary hyperparathyroidism (PHPT) patients ineligible for parathyroidectomy (PTX). Here we compared the clinical manifestations and characteristics of parathyroid glands in these two groups, and summarized the techniques, safety and efficacy of MWA.Methods: Baseline clinical characteristics, ablation-related techniques, adverse events/complications, and efficacy were recorded.Results: In SHPT group, malnutrition, cardiovascular/pulmonary complications, and abnormal bone metabolism were severe. SHPT patients had more hyperplastic parathyroid glands. The volume of each gland was smaller, and the time of ablation for a single parathyroid was shorter in the SHPT group, although there were no significant differences compared with patients in the PHPT group. Three patients in both groups had recurrent laryngeal nerve injuries and all recovered, except for one SHPT patient. By the end of follow-up, serum iPTH levels had decreased from 2400.26 ± 844.26 pg/mL to 429.39 ± 407.93 pg/mL (p < .01) in SHPT and from 297.73 ± 295.32 pg/mL to 72.22 ± 36.51 pg/mL in PHPT group (p < .01). Hypocalcemia was more common (p < .001) and serum iPTH levels were prone to rebound in SHPT patients after MWA.Conclusion: MWA can be reserved for those who had high surgical risks because of less invasiveness. Injuries of recurrent laryngeal nerves should be noticed. The health status, perioperative, and intraoperative procedures were more complicated and all parathyroids found by ultrasound should be ablated completely in SHPT patients.

The Impact of Frequency Scale on the Response Sensitivity and Reliability of Cortical Neurons to 1/fß Input Signals.

What type of principle features intrinsic inside of the fluctuated input signals could drive neurons with the maximal excitations is one of the crucial neural coding issues. In this article, we examined both experimentally and theoretically the cortical neuronal responsivity (including firing rate and spike timing reliability) to input signals with different intrinsic correlational statistics (e.g., white-type noise, showed 1/f0 power spectrum, pink noise 1/f, and brown noises 1/f2) and different frequency ranges. Our results revealed that the response sensitivity and reliability of cortical neurons is much higher in response to 1/f noise stimuli with long-term correlations than 1/f0 with short-term correlations for a broad frequency range, and also higher than 1/f2 for all frequency ranges. In addition, we found that neuronal sensitivity diverges to opposite directions for 1/f noise comparing with 1/f0 white noise as a function of cutoff frequency of input signal. As the cutoff frequency is progressively increased from 50 to 1,000 Hz, the neuronal responsiveness increased gradually for 1/f noise, while decreased exponentially for white noise. Computational simulations of a general cortical model revealed that, neuronal sensitivity and reliability to input signal statistics was majorly dominated by fast sodium inactivation, potassium activation, and membrane time constants.

US-guided microwave ablation for primary hyperparathyroidism: a safety and efficacy study.

OBJECTIVES: To evaluate the safety and efficacy of microwave ablation (MWA) with the assistance of continuous cool saline injection (CCSI) in patients with primary hyperparathyroidism (PHPT). METHODS: Between November 1, 2014, and February 29, 2016, 22 patients with PHPT were enrolled and treated with ultrasound-guided MWA assisted by CCSI. The levels of parathyroid hormone (PTH) and serum calcium were recorded before and after the MWA. Patients were divided into two groups (normalized and unnormalized groups) according to treatment efficacy. Fisher's exact test and the Mann-Whitney test were used to compare data between the two groups. Timing differences in serum PTH and calcium levels were analyzed with repeated measures analysis of variance. RESULTS: Normalized outcomes for both PTH and calcium levels were achieved in 19 of 22 (86.36%) patients with PHPT. In the normalized group, PTH levels remained normal for 12 months after MWA. PTH levels in the unnormalized group were outside the reference range at six of seven follow-ups within 12 months following MWA. By contrast, serum calcium levels gradually decreased in all patients in both groups. The mean serum PTH and mean calcium levels at 6 months after therapy were significantly lower than those before MWA (both p < 0.05). A transient voice change developed in eight patients. One patient experienced hypocalcaemia, which was corrected by oral calcium supplementation within 2 months. CONCLUSIONS: US-guided MWA assisted by CCSI is safe and effective for destroying parathyroid gland tissue and may serve as a therapeutic alternative for patients with PHPT. KEY POINTS: • Microwave ablation is a new option for patients with hypercalcemic or normocalcemic primary hyperparathyroidism. • Microwave ablation can decrease PTH and calcium levels with sustained efficacy in most patients. • Treatment is safe and causes only transient side effects.

Handgrip exercise reduces peripherally-inserted central catheter-related venous thrombosis in patients with solid cancers: A randomized controlled trial.

BACKGROUND: Peripherally-inserted central catheter-related venous thrombosis has serious complications including the loss of vascular access, recurrent venous thrombosis, and post-thrombotic syndrome. Current guidelines recommend non-pharmacological strategies to prevent peripherally-inserted central catheter-related venous thrombosis. There is little evidence for the effectiveness of handgrip exercise on the prevention of peripherally-inserted central catheter-related venous thrombosis. OBJECTIVES: To examine the effectiveness of handgrip exercise using an elastic ball to prevent peripherally-inserted central catheter-related venous thrombosis in patients with solid cancers. DESIGN: A randomized controlled trial. SETTINGS: One teaching hospital in Nanjing, China. PARTICIPANTS: In total, 120 subjects with solid cancers were eligible; each had a new peripherally-inserted central catheter. They were recruited and randomly assigned into two exercise groups and one control group. METHODS: Subjects from exercise groups 1 and 2 performed a 3-week, 25-repetition handgrip exercise, 3 and 6 times daily, respectively. The control group subjects performed a gentle limb exercise with no frequency and intensity requirements. Ultrasound was used to detect venous thrombosis development and examine axillary vein blood flow over the three points. RESULTS: There were 32 cases of peripherally-inserted central catheter-related venous thrombosis detected. Two venous thrombosis cases in the control group were symptomatic, but all venous thrombosis cases in the exercise groups were asymptomatic. All venous thromboses were partial. There were significant differences in the incidence of venous thrombosis among the three groups (χ2 = 12.813, p = 0.002; χ2 = 9.340, p = 0.009; χ2 = 11.480, p = 0.003; and χ2 = 10.534, p = 0.005, respectively) at days 2, 3 and 21. The incidence of venous thrombosis in the two exercise groups was lower than that in the control group over the 3 time points (all, p < 0.05). The between-group effects and interaction effect in vein maximum velocity and time-mean flow velocity showed significant differences (F = 4.180, p = 0.025; F = 4.010, p = 0.045; and F = 2.928, p = 0.025) at days 2, 3, and 21, respectively. The axillary vein blood flow parameters in the control group were lower than those in the two exercise groups at day 21 (all, p < 0.05). However, no significant differences occurred in the incidence of venous thrombosis and axillary vein blood flow parameters between the two exercise groups. CONCLUSION: Handgrip exercise using an elastic ball daily for three weeks could decrease the incidence of peripherally-inserted central catheter-related venous thrombosis. The method is simple, with no negative consequence reported. Further studies are required to confirm this conclusion and to explore the optimal frequency of handgrip exercise.