The Value of Contrast-Enhanced Ultrasound in the Detection of Sentinel Lymph Nodes in Malignant Melanoma.

OBJECTIVE: To evaluate the location and characterization value of contrast-enhanced ultrasound (CEUS) in the detection of sentinel lymph nodes (SLNs) in malignant melanoma. METHODS: SLNs and the lymph node network were tracked by subcutaneous injection of ultrasonic contrast agent around the tumor and preoperative localization, and qualitative analyses were performed. The SLNs were also detected by the intraoperative subcutaneous injection of carbon nanoparticles, and the findings were compared with lymph nodes located by CEUS. The accuracy of the preoperative lymph node identification was evaluated by the results of postoperative pathology, which served as the gold standard of detection. RESULTS: In 47 patients with malignant melanoma, the mean number of SLNs detected by CEUS was 1.72 ± 0.10, while that by carbon nanoparticle administration it was 1.79 ± 1.07 (P = .371 > .05). Seven cases of lymph node metastasis were detected by CEUS, with a sensitivity of 70.0%, specificity of 97.3%, positive predictive value of 87.5%, negative predictive value of 92.3%, and accuracy of 91.5%. There was high consistency between the findings of CEUS and pathology in differentiating benign and malignant lymph nodes (kappa = 0.726, χ2  = 25.243, P < .001). CONCLUSIONS: CEUS can localize and differentiate SLNs in malignant melanoma, and thus, may potentially guide clinical treatment in the future.

Monitoring of pH changes in a live rat brain with MoS2/PAN functionalized microneedles.

Monitoring the dynamic pH changes in vivo remains very essential to comprehend the function of pH in various physiological processes. In this study, we report a high-performance electrochemical pH microneedle based on an acupuncture needle (AN) for real-time monitoring of pH changes in a rat brain. The pH microneedle was prepared by a layer-to-layer assembly of molybdenum disulfide (MoS2) nanosheets and polyaniline (PAN), with an attempt to achieve a highly sensitive detection of hydrogen ions (H+). The as-prepared PAN/MoS2/AN exhibited a high Nernstian response of -51.2 mV per pH over a wide pH range from 3.0 to 9.0, and excellent selectivity toward pH against other potential interfering species in the brain. Moreover, the corresponding open circuit potential rapidly increased and decreased when Na2CO3 or NaH2PO4 was injected into the rat brain, respectively, demonstrating that the PAN/MoS2/AN has an excellent response toward pH changes in vivo. This work provides a new potentiometric method for real-time monitoring of dynamic pH changes in vivo with high reliability and stability.

MoS2/Pt nanocomposite-functionalized microneedle for real-time monitoring of hydrogen peroxide release from living cells.

This work describes the adaptive use of a conventional stainless steel acupuncture needle as the electrode substrate for construction of a molybdenum disulfide (MoS2) and platinum nanoparticles (PtNPs) layer-modified microneedle sensor for real-time monitoring of hydrogen peroxide (H2O2) release from living cells. To construct the nanocomposite-functionalized microneedle, the needle surface was first coated with a gold film by ion sputtering to enhance the conductivity. Subsequently, an electrochemical deposition method was successfully employed to deposit MoS2 nanosheet and Pt nanoparticles on the needle tip as the sensing interface. Electrochemical study demonstrated that the MoS2/PtNPs nanocomposite-modified needle exhibited excellent catalytic performance and low over-potential toward the reduction of H2O2. Not only did the microneedle achieve a wide linear range from 1 to 100 µmol L-1 with a limit of detection down to 0.686 µmol L-1, but it also realized the highly specific detection of H2O2. Owing to these remarkable analytical advantages, the prepared microneedle was applied to determine H2O2 release from living cells with satisfactory results. The MoS2/PtNPs nanocomposite-functionalized microneedle sensor is simple and affordable, and can serve as a promising electrochemical nonenzymatic sensing platform. Moreover, this superfine needle sensor shows great potential for real-time monitoring of reactive oxygen species in vivo with minimal damage.

[Diagnostic value of Kimura's disease with ultrasonography].

OBJECTIVE: To explore the diagnostic value of ultrasonography for Kimura's disease (KD). METHODS: Retrospectively analyzed the results of two dimension and color Doppler of 21 Kimura's disease carried by 19 patients who were resected and confirmed by pathologhy. RESULTS: Twenty-one KD cases were detected by the ultrasound while none of them was diagnosed by ultrasonography. 21 cases were showed in the lymph nodes (42.9%, 9/21), parotid gland (4.8%, 1/21) and soft tissues (52.4%, 11/21). The masses both in the lymph and in the parotid gland marked hypoechogenicity and round or like-round. Cases in the soft tissues marked hypoechogencity or hyperechogenicity. Color Doppler flow pattern II to III were showed in 19 cases (90.5%, 19/21). CONCLUSION: Ultrasonography enables a confident preoperative diagnosis of Kimura's disease.

The role of anti-VEGF agents in the treatment of advanced gastric cancer: a meta-analysis of randomized controlled trials.

Inhibition of vascular epithelial growth factor (VEGF) signaling pathways has proven to be an effective strategy for the treatment of several common solid tumors, but its role in the management of advanced gastric cancer (AGC) is yet to be defined. We performed a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and safety of anti-VEGF agents in the treatment of AGC. Several databases were searched, including PubMed, Embase, and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3 or 4 adverse events (AEs). The pooled hazard ratio (HR) or relative risk (RR) and 95 % confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Seven RCTs which involved 2,340 patients were ultimately identified. The pooled analysis demonstrated that anti-VEGF therapy significantly improved OS (HR 0.74, 95 % CI 0.61-0.91, p = 0.003), PFS (HR 0.59, 95 % CI 0.44-0.78, p < 0.001), and ORR (RR 1.43, 95 % CI 1.14-1.79, p = 0.002) when compared to non-anti-VEGF therapy. Sensitivity analysis further confirmed this association. Additionally, more incidences of grade 3 or 4 thrombocytopenia, diarrhea, and hypertension were observed in anti-VEGF therapy. The anti-VEGF therapy offers a significant survival benefit in patients with AGC, especially for those previously treated patients, when compared to non-anti-VEGF therapy. With the present available data from randomized clinical trials, we could not clearly set the role of specific anti-VEGF agents in the treatment of AGC. Further studies are recommended to identify patients who could derive greater benefits from specific anti-VEGF agents.

Congestive heart failure risk in cancer patients treated with vascular endothelial growth factor tyrosine kinase inhibitors: a systematic review and meta-analysis of 36 clinical trials.

AIMS: Congestive heart failure (CHF) associated with vascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) has emerged as a relevant problem in clinical and scientific communities. We performed an up-to-date, comprehensive meta-analysis to determine the overall incidence and risk of CHF in cancer patients receiving VEGFR-TKIs. METHODS: The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to August 31 2013 were searched for relevant articles. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies. RESULTS: A total of 10 553 patients from 36 clinical trials were included. The overall incidence of all grade and high grade CHF associated with VEGFR-TKIs was 3.2% (95% CI 1.8%, 5.8%) and 1.4% (95% CI 0.9%, 2.3%), respectively. The use of VEGFR-TKIs significantly increased the risk of developing all grade (OR 2.37, 95% CI 1.76, 3.20, P < 0.001) and high grade (OR 3.51, 95% CI 1.74, 7.05, P < 0.001) CHF. In subgroup analyses, the risk of CHF did not significantly vary with tumour types (P = 0.071 for all grade; P = 0.72 for high grade) and VEGFR-TKIs (P = 0.55 for all grade; P = 0.99 for high grade). Meta-regression indicated that CHF might possibly occur early in the treatment of VEGFR-TKIs. No evidence of publication bias was observed. CONCLUSION: The use of VEGFR-TKIs is associated with a significantly increased risk of developing congestive heart failure in cancer patients. Clinicians should be aware of this risk and provide close monitoring in patients receiving these therapies.

Bevacizumab increases the risk of gastrointestinal perforation in cancer patients: a meta-analysis with a focus on different subgroups.

BACKGROUND: The aim of this meta-analysis was to gather current data and evaluate not only the risk of gastrointestinal (GI) perforation with bevacizumab, but also the potential risk factors for this adverse event. MATERIALS AND METHODS: We carried out a literature search in PubMed for randomized controlled trials (RCTs) reported from January 2000 to December 2013. Summary incidence, relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies. RESULTS: A total of 26,833 patients from 33 RCTs were included in the meta-analysis. Bevacizumab-containing therapy significantly increased the risk of developing all-grade (RR 3.35, 95% CI 2.35-4.79, P < 0.001) and fatal GI perforation (RR 3.08, 95%CI: 1.04-9.08, P = 0.042). On subgroup analysis, no significant risk differences were found based on bevacizumab dosage, treatment duration, treatment line, type of clinical trial and median age. When stratified by tumor types, a significantly increased risk of GI perforation with bevacizumab was observed in colorectal cancer (RR 2.84, 95% CI 1.43-5.61, P = 0.003), gynecologic cancer (RR 3.37, 95% CI 1.71-6.62, P < 0.001) and prostate cancer (RR 6.01, 95% CI 1.78-20.28, P = 0.004). Additionally, the use of bevacizumab significantly increased the risk of GI perforation when used in conjunction with taxanes (RR 3.09, 95% CI 1.92-4.96, P < 0.001) or oxaliplatin (RR 2.85, 95% CI 1.07-7.57, P = 0.036). CONCLUSIONS: Bevacizumab treatment is associated with a significantly increased risk of developing GI perforation, and clinicians should be aware of the risks of GI perforation with the administration of this drug in cancer patients.

Treatment-related mortality with aflibercept in cancer patients: a meta-analysis.

PURPOSE: Aflibercept, a fully humanized vascular endothelial growth factor (VEGF)-targeted agent, has emerged as an effective therapy in the treatment of various solid tumors. We carried out an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in cancer patients treated with aflibercept. METHODS: We searched databases such as PubMed and Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) meetings for records up to August 2013 to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating aflibercept in cancer patients with adequate data on FAEs. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95 % confidence intervals (CIs) by using either random effects or fixed-effect models according to the heterogeneity of included studies. RESULTS: A total of 3,060 patients with a variety of solid tumors from ten clinical trials were included in our analysis. The overall incidence of FAEs associated with aflibercept was 5.1 % (95%CI: 3.8-6.8 %). The use of aflibercept significantly increased the risk of FAEs compared to patients treated with control medication (OR 1.81, 95 % CI: 1.20-2.72, p = 0.004). Additionally, the most common causes of FAEs were infection (38.8 %), hemorrhage (5.9 %) and GI perforation (5.9 %), respectively. CONCLUSIONS: With available evidence, the use of aflibercept is associated with an increased risk of FAEs compared to controls. Further studies are still needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept remains justified in its approved indications.

Risk of osteonecrosis of the jaw in cancer patients receiving denosumab: a meta-analysis of seven randomized controlled trials.

AIMS: The aim of this study is to gain a better understanding of the overall incidence and risk of osteonecrosis of the jaw (ONJ) in cancer patients receiving denosumab. METHODS: We performed a meta-analysis of relevant randomized controlled trials identified in Pubmed, Embase, and Cochrane databases. Abstracts presented at the conferences were also searched. Overall incidence rates, relative risk (RR), and 95 % confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. RESULTS: A total of 8963 patients with a variety of solid tumors from 7 randomized controlled trials (RCTs) were included for the meta-analysis. The overall incidence of ONJ in cancer patients receiving denosumab was 1.7 % [95 % CI: 0.9-3.1 %]. Also, the use of denosumab was associated with significantly increased risk of ONJ in comparison with bisphosphonates (BPs)/placebo treatment (RR 1.61, 95 % CI: 1.05-2.48, P = 0.029). Subgroup analysis based on controlled therapies demonstrated an increased risk of ONJ in denosumab therapy, when compared with BPs (RR 1.48, 95 % CI: 0.96-2.29, P = 0.078) or placebo (RR 16.28, 95 % CI: 1.68-158.05, P = 0.017). Similar results were observed in prostate cancer (RR 3.358, 95 % CI: 1.573-7.166, P = 0.002) while there was a non-significantly increased risk of denosumab-related osteonecrosis of the jaw (DONJ) in non-prostate cancers (RR 1.142, 95 % CI: 0.678-1.921, P = 0.618). CONCLUSIONS: The use of denosumab is associated with an increased risk of developing ONJ when compared with BP treatment or placebo, although the increased risk was not statistically significant between denosumab and BP treatment. Further studies are still needed to establish guidelines for the prevention and effective treatment of ONJ.

Herbal Insomnia Medications that Target GABAergic Systems: A Review of the Psychopharmacological Evidence.

Insomnia is a common sleep disorder which is prevalent in women and the elderly. Current insomnia drugs mainly target the γ-aminobutyric acid (GABA) receptor, melatonin receptor, histamine receptor, orexin, and serotonin receptor. GABAA receptor modulators are ordinarily used to manage insomnia, but they are known to affect sleep maintenance, including residual effects, tolerance, and dependence. In an effort to discover new drugs that relieve insomnia symptoms while avoiding side effects, numerous studies focusing on the neurotransmitter GABA and herbal medicines have been conducted. Traditional herbal medicines, such as Piper methysticum and the seed of Zizyphus jujuba Mill var. spinosa, have been widely reported to improve sleep and other mental disorders. These herbal medicines have been applied for many years in folk medicine, and extracts of these medicines have been used to study their pharmacological actions and mechanisms. Although effective and relatively safe, natural plant products have some side effects, such as hepatotoxicity and skin reactions effects of Piper methysticum. In addition, there are insufficient evidences to certify the safety of most traditional herbal medicine. In this review, we provide an overview of the current state of knowledge regarding a variety of natural plant products that are commonly used to treat insomnia to facilitate future studies.

[Evaluation of the sedative and hypnotic effects of H1208].

This study is to investigate the sedative and hypnotic effects of a novel compound H1208. The sedative activity of H1208 was investigated by recording the spontaneous locomotor activity of mice. The hypnotic property was evaluated by the latency and duration of sleep (loss of righting reflex) in mice and the effect of hypnotics on sleep pattern of electroencephalogram were studied in conscious, freely moving mice with chronically implanted electrodes. The brain monoamine neurotransmitters levels in mice were measured by high performance liquid chromatography-electrochemical detection. The spontaneous locomotor activity was decreased by 56.7% and 80.2% in H1208 (5 and 25 mg x kg(-1), ip) treated mice, respectively. The loss of righting reflex was directly induced in mice after H1208 (60 mg x kg(-1), ip) administration. The non-rapid eye movement sleep increased significantly by 131% and 259%, respectively, within 3 hours after H1208 (30 and 60 mg x kg(-1), ip) administration. However, the rapid eye movement sleep decreased significantly. The contents of DA in the striatum and cortex and 5-HT in the cortex decreased significantly. These results demonstrated that H1208 has potent sedative and hypnotic effects, which may be closely related to the decreased contents of DA and 5-HT in mouse brain.

Nomogram Based on US and Clinicopathologic Characteristics: Axillary Nodal Evaluation Following Neoadjuvant Chemotherapy in Patients With Node-Positive Breast Cancer.

BACKGROUND: To develop a convenient modality to predict axillary response to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: In this multi-center study, a total of 1019 breast cancer patients with biopsy-proven positive lymph node (LN) receiving NAC were randomly assigned to the training and validation groups at a ratio of 7:3. Clinicopathologic and ultrasound (US) characteristics of both primary tumors and LNs were used to develop corresponding prediction models, and a nomogram integrating clinicopathologic and US predictors was generated to predict the axillary response to NAC. RESULTS: Axillary pathological complete response (pCR) was achieved in 47.79% of the patients. The expression of estrogen receptor, human epidermal growth factor receptor -2, Ki-67 score, and clinical nodal stage were independent predictors for nodal response to NAC. Location and radiological response of primary tumors, cortical thickness and shape of LNs on US were also significantly associated with nodal pCR. In the validation cohort, the discrimination of US model (area under the curve [AUC], 0.76) was superior to clinicopathologic model (AUC, 0.68); the combined model (AUC, 0.85) demonstrates strong discriminatory power in predicting nodal pCR. Calibration curves of the nomogram based on the combined model demonstrated that substantial agreement can be observed between the predictions and observations. This nomogram showed a false-negative rates of 16.67% in all patients and 10.53% in patients with triple negative breast cancer. CONCLUSION: Nomogram incorporating routine clinicopathologic and US characteristics can predict nodal pCR and represents a tool to aid in treatment decisions for the axilla after NAC in breast cancer patients.

Alterations in Serum Lipids and Lipoproteins Induced by Neoadjuvant Chemotherapy in Patients with Osteosarcoma around the Knee Joint: A Retrospective Analysis.

OBJECTIVE: To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy. METHODS: After retrospectively screening the data of 742 patients between January 2007 and July 2020, 50 patients aged 13 to 39 years with Enneking stage II disease were included in the study. Serum lipid levels, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein-α [Lp(a)], and apolipoprotein A1, B, and E (ApoA1, ApoB, and ApoE), and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy. RESULTS: The mean levels of TC, TG, and ApoB were significantly increased following neoadjuvant chemotherapy (16%, 38%, and 20%, respectively, vs. pretreatment values; P<0.01). The mean levels of LDL-C and ApoE were also 19% and 16% higher, respectively (P<0.05). No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy. An increase in Lp(a) was strongly correlated with the Ki-67 index (R=0.31, P=0.023). Moreover, a trend toward longer disease-free survival (DFS) was observed in patients with decreased TG and increased LDL-C following chemotherapy, although this difference was not statistically significant (P=0.23 and P=0.24, respectively). CONCLUSION: Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma. There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy. The scale of increase in serum Lp(a) might have a potential prognostic role in osteosarcoma. Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.

Overall survival benefits for irinotecan-containing regimens as first-line treatment for advanced gastric cancer: an updated meta-analysis of ten randomized controlled trials.

The standard treatment for patients with advanced gastric cancer (AGC) is still debated, and the available data on the benefit of irinotecan-containing regimen as first-line treatment for those patients are controversial. We performed a systematic review and meta-analysis of randomized controlled trials to determine the survival benefits of irinotecan-containing regimens in this setting. A total of 1,837 patients from ten trials were included in the analysis. Our results showed that irinotecan-containing regimens significantly improved overall survival [OS: hazard ratio (HR) 0.86, 95% CI = 0.78-0.94, p = 0.002] and progression-free survival [HR = 0.82, 95% CI = 0.69-0.97, p = 0.026); however, the improvement of time to failure (HR = 0.90; 95% CI = 0.77-1.04, p = 0.15), 1-year survival rate [1-year SR: relative risk (RR) 1.10, 95% CI = 0.97-1.24, p = 0.13] and overall response rate (RR = 1.16, 95% CI = 0.91-1.49, p = 0.24] were nonsignificant. Equivalent frequencies of toxicities were found between the two groups excluding more Grade 3 or 4 fatigue (p = 0.001) in irinotecan-containing regimens. This updated meta-analysis provided strong evidence for a survival benefit of irinotecan-containing regimen as first-line treatment for AGC. A clear advantage of irinotecan-containing over nonirinotecan-containing regimen had not been established. These results should help to inform decisions about patient management and design of future trials.

Risk of venous thromboembolic events associated with VEGFR-TKIs: a systematic review and meta-analysis.

Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have been widely used in advanced cancers. Concerns have arisen regarding the risk of venous thromboembolism with the use of these drugs. Currently, the contribution of VEGFR-TKIs to venous thromboembolism is still unknown. We performed a meta-analysis to determine the incidence and relative risk (RR) of venous thromboembolism events (VTEs) associated with these agents. Eligible studies included phase II and III prospective trials evaluating US Food and Drug Administration approved VEGFR-TKIs (pazopanib, sunitinib, sorafenib and vandetanib), and data on VTEs were available. Overall incidence rates, RR and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of included trials. A total of 14 studies (4,430 patients) were selected for this meta-analysis. The incidence of VTEs related to VEGFR-TKIs was 3% (95%CI: 1.7-5.1%), and there was no statistically significant increase in the risk of VTEs for VEGFR-TKIs versus controls in overall population (RR0.912, 95%CI: 0.617-1.348, p = 0.643). On subgroup analysis, no significant increase in the risk of VTEs was found among different VEGFR-TKIs or tumor types. No evidence of publication bias was observed. The use of VEGFR-TKIs does not significantly increase the risk of VTEs, the risk of VTEs in patients with cancer is driven predominantly by tumor types, host factors and concomitant usage of anticancer agents. These results would provide important information for clinicians who use VEGFR-TKIs to treat patients with solid cancer.

Risk of venous and arterial thromboembolic events in cancer patients treated with gemcitabine: a systematic review and meta-analysis.

AIMS: Gemcitabine has been associated with an increased risk of arterial and venous thromboembolic events (ATEs and VTEs), although the overall risk remains unclear. As indications for its use in oncology are expanding, a comprehensive characterization of these complications becomes imperative. METHODS: Pubmed was searched for articles published from 1 January 1990 to 31 December 2012. Eligible studies included prospective randomized controlled phase II and III trials evaluating gemcitabine based vs. non-gemcitabine based chemotherapy in patients with solid tumours. Data on VTEs and ATEs were extracted. Overall incidence rates, odds ratio (OR), and 95% confidence intervals (CIs) were calculated employing fixed or random effects models depending on the heterogeneity of included trials. RESULTS: A total of 4845 patients from 19 trials were included. Among patients treated with gemcitabine based chemotherapy, the overall incidence of VTEs (13 studies comprising 3823 patients) and ATEs (eight studies consisting of 2431 patients) was 2.1% (95% CI 1.2%, 3.8%) and 2.2% (95% CI 1.4%, 3.2%). The associated ORs of VTEs and ATEs were 1.56 (95% CI 0.86, 2.83, P = 0.15) and 1.82 (95% CI 0.89, 3.75, P = 0.10) compared with non-gemcitabine based therapy. A tendency to increase the risk of ATE and VTEs was also detected in any prespecified subgroup. CONCLUSION: The use of gemcitabine does not significantly increase the risk of VTEs and ATEs in patients with solid tumours when compared with non-gemcitabine based chemotherapy.

Incidence and risk of hypertension with vandetanib in cancer patients: a systematic review and meta-analysis of clinical trials.

AIM: To perform a systematic review and meta-analysis of published clinical trials to determine incidence rate and overall risk of hypertension with vandetanib in cancer patients. METHODS: A comprehensive literature search for studies published up to March 2012 was performed. Summary incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. RESULTS: A total of 11 trials with 3154 patients were included for the meta-analysis. The summary incidences of all-grade and high-grade hypertension in patients with cancer were 24.2% [95% confidence interval (CI), 18.1-30.2%] and 6.4% (95% CI, 3.3-9.5%), respectively. Subgroup analysis demonstrated that the pooled incidences of all-grade and high-grade hypertension were 21.8% [95% CI, 15-30.5%] and 7.6% (95% CI, 2.8-18.8%), respectively, among non-small-cell lung cancer (NSCLC) patients, and 32.1% (95% CI: 27.3-37.3%) and 8.8% (5.9%-12.9%), respectively, among MTC patients, and 15.4 (95% CI: 3.2-33.7%) and 3.4% (95% CI: 1%-11.1%) respectively, among non-MTC/NSCLC tumors patients. Furthermore, vandetanib was associated with a significant increased risk of all-grade hypertension (RR 5.1, 95% CI: 3.76-6.92, P = 0.000) and high-grade hypertension (RR 8.06, 95% CI: 3.41-19.04, P = 0.000) in comparison with controls. CONCLUSIONS: There is a significant risk of developing hypertension in cancer patients receiving vandetanib. Appropriate monitoring and treatment is strongly recommended to prevent cardiovascular complications.

Efficacy of Children Neuropsychological and Behavioral Scale in Screening for Autism Spectrum Disorders through a Combination of Developmental Surveillance.

OBJECTIVE: This study aimed to explore the clinical value of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) for Autism Spectrum Disorder (ASD) screening in the presence of developmental surveillance. METHODS: All participants were evaluated by the CNBS-R2016 and Gesell Developmental Schedules (GDS). Spearman's correlation coefficients and Kappa values were obtained. Taking GDS as a reference assessment, the performance of the CNBS-R2016 for detecting the developmental delays of children with ASD was analyzed with receiver operating characteristic (ROC) curves. The efficacy of the CNBS-R2016 to screen for ASD was explored by comparing Communication Warning Behavior with Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). RESULTS: In total, 150 children aged 12-42 months with ASD were enrolled. The developmental quotients of the CNBS-R2016 were correlated with those of the GDS (r=0.62-0.94). The CNBS-R2016 and GDS had good diagnostic agreement for developmental delays (Kappa=0.73-0.89), except for Fine Motor. There was a significant difference between the proportions of Fine Motor, delays detected by the CNBS-R2016 and GDS (86.0% vs. 77.3%). With GDS as a standard, the areas under the ROC curves of the CNBS-R2016 were above 0.95 for all the domains except Fine Motor, which was 0.70. In addition, the positive rate of ASD was 100.0% and 93.5% when the cut-off points of 7 and 12 in the Communication Warning Behavior subscale were used, respectively. CONCLUSION: The CNBS-R2016 performed well in developmental assessment and screening for children with ASD, especially by Communication Warning Behaviors subscale. Therefore, the CNBS-R2016 is worthy of clinical application in children with ASD in China.

Efficacy and safety of gemcitabine-docetaxel combination therapy for recurrent or refractory high-grade osteosarcoma in China: a retrospective study of 18 patients.

OBJECTIVE: In this study, we describe experiences with gemcitabine-docetaxel combination therapy as salvage treatment for Chinese patients with recurrent or refractory high-grade osteosarcoma. METHODS: We retrospectively reviewed the medical records of 18 patients with recurrent or refractory high-grade osteosarcoma who had undergone gemcitabine-docetaxel combination treatment as salvage chemotherapy. Gemcitabine at 675 mg/m(2) was administered on Days 1 and 8, and docetaxel at 75-100 mg/m(2) was administered on Day 8. The combination therapy was repeated every 3 weeks. Treatment was continued until evidence of disease progression or unacceptable toxicity. RESULTS: The patients (ages 12-57 years) received a total of 44 cycles of chemotherapy (median: 2 courses; range: 2-6 courses). The overall response rate was 5.6% and the disease control rate was 22.3%, with one partial response and three patients with stable disease. The median time to progression and overall survival time were 2 months (range: 2-6 months) and 8 months (range: 3-21 months), respectively. Major severe toxicities were hematologic toxicities, including Grade 3 or 4 anemia (9.1%), leucopenia (29.5%) and thrombocytopenia (18.1%) in total cycles; mild toxicities included Grade 1 or 2 nausea and vomiting (31.8%), fatigue (38.6%) and alopecia (20.5%). There were no treatment-related deaths. CONCLUSIONS: In the current study, gemcitabine-docetaxel combination therapy at this dosage and schedule was found to be well tolerated and marginally effective, which could be considered as salvage therapy for patients with recurrent or refractory high-grade osteosarcoma.

BAP1 is a good prognostic factor in advanced non-small cell lung cancer.

PURPOSE: Non-small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting epidermal growth factor receptor (EGFR) mutations have been developed, most advanced NSCLC is still incurable and new targets for anticancer drugs are in demand. BRCA1-associated protein-1 (BAP1) is a component of the ubiquitin proteasome system (UPS). UPS has emerged as a potential target for anticancer drugs. The aim of the present study was to investigate the expression of BAP1 protein in patients with NSCLC. METHODS: BAP1 expression was measured using Western blot analysis in 103 cases patients with advanced NSCLC. RESULTS: Results revealed 49 (47.5%) patients were classified with high expression of BAP1. Squamous cell carcinomas were more likely to be observed in BAP1 high expressers compared with adenocarcinomas (55.8% vs. 32.3%, p = 0.001). High BAP1 expression was associated with no lymph node metastasis (p = 0.002). There was also a significant association between BAP1 expression and histological type (p = 0.014), while expression of BAP1 was not correlated with other clinical or pathological characteristics. Kaplan-Meier survival analysis showed that patients with high BAP1 expression had a longer median survival compared with patients with low BAP1 expression (23.2 vs. 14.7 months, p = 0.021). Multivariate analysis revealed that high BAP1 expression was an independent lower risk for all 103 patients (HR = 0.61, 95% CI 0.32-0.71, p = 0.003). CONCLUSIONS: BAP1 may be a useful prognostic factor of NSCLC patients and potential target for anticancer drugs.