Gabapentin enhances the antinociceptive effect of intrathecal morphine in refractory cancer pain patients.

PURPOSE: Morphine infusion through Intrathecal Drug Delivery System (IDDS) is widely used to relieve refractory cancer pain. However, continuous escalation of morphine dose caused by opioid tolerance and/or progress of cancer was commonly observed. Combining morphine with medications of different analgesic mechanisms is applied to blunt the rate of morphine increase. The purpose of this study was to determine the analgesic efficacy and safety of combining gabapentin with morphine after IDDS implantation. METHODS: This study compared patients that received IDDS implantation from January 1, 2017 to November 10, 2018 in our institute. Key outcomes included change in mean pain score, dose of morphine used in patients, percentage of patients with 30% and 50% reduction in mean pain score, Patient Global Impression of Change scores, breakthrough pain characters and side effects. RESULTS: 34 patients in the combination group (morphine + gabapentin) and 40 patients in the monotherapy group(morphine)were analyzed. The results showed that both therapy groups achieved similar analgesic efficacy, demonstrated by Numerical rating scale (2.42 ± 0.88 vs 2.57 ± 0.85; Combination vs Monotherapy), PGIC and responder status. Mean daily dose of morphine was significantly lower in combination group compared to monotherapy group (3.54 ± 1.29 mg vs 4.64 ± 1.28 mg, P = 0.007). More patients experienced dizziness and somnolence after receiving combination therapy compared to morphine-alone treatment although no statistical significance was found (P = 0.49). CONCLUSION: Addition of gabapentin achieved similar analgesic efficacy with lower dose of morphine compared to morphine alone accompanying with higher incidence of dizziness and somnolence.

Negative Impact of Intra-Operative Blood Transfusion on Survival Outcomes of Hepatocellular Carcinoma Patients.

Background: Studies have reported that blood transfusion may have an association with survival outcomes of cancer patients. This study was aimed at finding the effect of intra-operative blood transfusion on the prognosis of patients of hepatocellular carcinoma (HCC). Methods: This was a retrospective study. HCC patients who underwent tumor resection from January 2013 to November 2018 at Harbin Medical University Cancer Hospital were included. The survival time of patients receiving or not receiving blood transfusion during the operation were compared. Results: Of HCC patients, 21.1% (102/484) received intra-operative blood transfusion. After propensity score matching, 87 pairs of patients were included in the study. In the subset of patients with a tumor size of >4 cm, univariable analysis found that there were significant differences in recurrence-free survival (RFS; P=0.004) and overall survival (OS; P=0.028) between blood transfusion and non-blood transfusion groups. After multivariable Cox regression analysis, intra-operative blood transfusion was an independent risk factor for RFS (HR: 2.011, 95% CI: 1.146-3.529, P=0.015), but not for OS (HR: 1.862, 95% CI: 0.933-3.715, P=0.078) in the subset of patients with a tumor size of >4 cm. Conclusion: Intra-operative blood transfusion was associated with worse RFS in HCC patients with a tumor size of >4 cm.

Peripheral blood markers predict immunotherapeutic efficacy in patients with advanced non-small cell lung cancer: A multicenter study.

This study aims to investigate the prognostic impact of peripheral blood markers in patients with advanced non-small cell lung cancer (NSCLC) undergoing immunotherapy. In the current multicenter study, 157 advanced NSCLC cases treated by immunotherapy at three institutions were included. Biochemical parameters in baseline peripheral blood were collected. The associations between biochemical parameters and prognosis were investigated by the Kaplan-Meier survival analyses and Cox regression, and the predictive performances of biomarkers were evaluated via receiver operating characteristic analysis. The neutrophil-to-lymphocyte ratio (NLR) (progression-free survival [PFS]: hazard ratio [HR], 1.766; 95% confidence interval [CI], 1.311-2.380; p < 0.001; overall survival [OS]: HR, 1.283; 95% CI, 1.120-1.469; p < 0.001) and red blood cell distribution width (RDW) (PFS: HR, 1.052; 95% CI, 1.005-1.102; p = 0.031; OS: HR, 1.044; 95% CI, 1.001-1.091; p = 0.042) were revealed as independent predictors for both PFS and OS. In addition, NLR ≥3.79 (1-year PFS, 24.2% [95% CI, 15.2%-38.4%] versus 27.3% [95% CI, 18.2%-41.1%], p = 0.041; 1-year OS, 44.2% [95% CI, 32.5%-60.1%] versus 71.8% [95% CI, 60.6%-85.2%], p < 0.001) or RDW ≥44.8 g/L (1-year PFS, 19.2% [95% CI, 11.4%-32.3%] versus 31.7% [95% CI, 21.9%-46.0%], p = 0.049; 1-year OS, 54.0% [95% CI, 42.7%-68.3%] versus 63.1% [95% CI, 50.6%-78.6%], p = 0.014) was significantly correlated to poorer PFS and OS than NLR < 3.79 or RDW <44.8 g/L. Moreover, NLR and RDW achieved areas under the curve with 0.651 (95% CI, 0.559-0.743) and 0.626 (95% CI, 0.520-0.732) for predicting PFS, and 0.660 (95% CI, 0.567-0.754) and 0.645 (95% CI, 0.552-0.739), for OS. Therefore, PLR and RDW could help predict the immunotherapeutic efficacy of advanced NSCLC.

Dose of intra-operative opioids has no impact on recurrence or survival in primary liver cancer.

BACKGROUND: Intra-operative use of opioid analgesics might have an impact on cancer recurrence and survival after surgery. The objective of this study was to investigate the association between the intra-operative fentanyl equivalents and survival outcomes in patients with primary liver cancer after receiving hepatectomy. METHODS: This was a retrospective single-center cohort study, and clinical data of 700 patients with primary liver cancer who underwent hepatectomy in Harbin Medical University Cancer Hospital from September 2013 to August 2018 were reviewed. After propensity matching, 376 patients were included. Patients were divided into high-dose and low-dose groups according to the median intra-operative fentanyl equivalents (1.500 mg). Kaplan Meier curve and Cox proportional hazards regression model were used. RESULTS: Results of univariable analysis showed there were no significant differences in recurrence-free survival (RFS) (p = 0.136) and overall survival (OS) (p = 0.444) between high-dose fentanyl equivalents and low-dose fentanyl equivalents group. The multivariable Cox regression analysis found that the dose of intra-operative fentanyl equivalents was not associated with RFS (HR: 1.119, 95%CI: 0.851-1.472, p = 0.422) or OS (HR: 0.939, 95%CI: 0.668-1.319, p = 0.715). CONCLUSIONS: The amounts of intra-operative fentanyl equivalents had no impact on recurrence-free or overall survival in patients with primary liver cancer after curative hepatectomy.

The combined analgesic effect of pregabalin and morphine in the treatment of pancreatic cancer pain, a retrospective study.

BACKGROUND: Pregabalin is commonly used to relieve neuropathic pain. However, data are lacking on its efficacy for the treatment of chronic cancer pain. The purpose of this study was to determine the analgesic efficacy of pregabalin combined with morphine in the management of pancreatic cancer pain. METHODS: This study reviewed patients who were prescribed morphine and 150 mg/d pregabalin between 1 January 2017 and 10 November 2018 in our institute. The primary outcomes of this study were the average pain score and dose of morphine. Secondary outcomes included characters of breakthrough cancer pain, functional interference related to pain, anxiety/depression status, and incidence of treatment-related adverse events during the study. RESULTS: A total of 240 patients with pain related to pancreatic cancer were included in the study. The results showed that patients of both combination therapy group (pregabalin+morphine) and monotherapy group (morphine) achieved similar analgesic efficacy, demonstrated by NRS (2.4 ± 0.9 vs. 2.6 ± 0.9; combination vs. monotherapy) at the end of the study. Mean daily dose of morphine used in the combination group was significant lower compared to monotherapy group (39.5 ± 16.0 mg vs. 61.5 ± 19.3 mg, net difference 23.5, 95% CI: 18.4-28.6, p < â€Š0.001). The change of functional interference score related to pain was significantly different between combination and monotherapy group (12.0 ± 0.4 vs. 9.8 ± 4.9; net difference, 2.3; 95% CI: 1.1-3.3; p < 0.001). Patients in combination therapy group had experienced shorter duration of breakthrough cancer pain than those in monotherapy group (X2 p < 0.001, Cramer's V:0.36). The incidence of somnolence, dizziness, and cognitive dysfunction were significantly higher in the combination group compared to monotherapy group. No serious treatment-related side effects were observed. CONCLUSIONS: The findings of this study supported the use of pregabalin with morphine to relieve pain in patients of pancreatic cancer.

Bone pain from spinal metastases: Iodine-125 brachytherapy.

OBJECTIVES: This study evaluated the analgesic efficacy and safety of CT-guided iodine-125 (125I) brachytherapy in patients with spinal metastasis-induced pain who were not suitable to receive radiotherapy. METHODS: A cohort of 68 patients with spinal metastasis induced pain not fully relieved by opioids and did not receive external beam radiation therapy due to poor general status were enrolled and underwent CT-guided 125I brachytherapy for analgesic treatment. RESULTS: Patients were followed for 8 weeks after brachytherapy. Mean Numerical Rating Scale score before brachytherapy was 7.3±1.3 and decreased to 3.3±0.9, 2.6±0.8, 2.7±0.8, 2.9±0.9 and 3.3±1.1 at weeks 1, 2, 4, 6 and 8, respectively, after brachytherapy. Daily dose of morphine equivalent was 105.1±28.0 mg before brachytherapy and decreased to 45.3±13.7, 39.9±14.2, 40.4±14.9, 48.5±18.0 and 62.4±17.5 mg at weeks 1, 2, 4, 6 and 8, respectively, after brachytherapy. Patients had fewer daily episodes of breakthrough pain after brachytherapy (p<0.001). Patients had improvement in pain-related functional interference and in hospital anxiety and depression score after brachytherapy. CONCLUSIONS: CT-guided 125I brachytherapy is an effective and safe intervention for patients with spinal metastasis-induced pain who are not able to receive radiation therapy.

Gridded emission inventory of organophosphorus flame retardants in China and inventory validation.

The bioaccumulation and adverse effects of organophosphorus flame retardants (OPFRs) on human health have become a global concern. China produces the largest amount of OPFRs globally and has the highest global market share. However, little is known about its emission level and environmental cycling, thereby causing uncertainties in the assessment of the environmental and health impacts of OPFRs. We developed a gridded annual OPFRs emission inventory at 1/4° longitude by 1/4° latitude resolution over China from 2014 to 2018. The results show that the annual OPFRs emissions increased from approximately 670 tons/yr in 2014 to 1000 tons/yr in 2018 in China. Higher OPFR emissions were identified in Jiangxi, Shandong, Beijing-Tianjin-Hebei (BTH), Yangtze River Delta (YRD), and Pearl River Delta (PRD). In total, 2400 tons of OPFRs were released into the atmosphere during the multi-year period, in which production accounting for 56.6% of total OPFR emissions in China. An atmospheric transport model, the Canadian Model for Environmental Transport of Organochlorine Pesticides (CanMETOP), was employed to verify the gridded emission inventory and elucidate the atmospheric environmental fate of OPFRs. Modeled OPFRs in the air and soil agreed reasonably well with observed data, suggesting that the developed inventory was, to a large extent, reliable. The modeled atmospheric and surface soil concentrations of OPFRs across China ranged from 0 to 119 ng/m3 and 0 to 428 ng/g, respectively. East China is subjected to more intense OPFR contamination than the rest of the country. The results provide a valuable dataset and assessment of OPFRs, which may aid policy-makers and the scientific community in developing emission control strategies and evaluating the health and environmental consequences of OPFRs in China.

Multiple exposure pathways of first-year university students to heavy metals in China: Serum sampling and atmospheric modeling.

In this study, we collected 308 serum samples from 17 to 20 year old first-year university students who were recruited from Lanzhou University in China a few days after their enrollment to measure the serum Pb, Cd, Hg, and As levels, and specific questionnaires for age, sex, settlement and dietary structure were designed. A 3-D atmospheric transport model was used to simulate the atmospheric concentration and dry deposition across China based on gridded Pb emission inventory to examine the association between the spatial distribution of serum concentrations and environmental fates of Pb. The mean serum Pb, Cd, Hg, and As concentrations averaged over all participating young students were 21.38, 1.46, 3.86, and 4.69 µg/L, respectively. The Pb, Cd, and Hg levels in 3%, 7%, and 20% serum samples exceeded the standards. The minimum serum As and Hg concentrations and the maximum serum Pb and Cd concentrations occurred in urban areas. Seafood diet habits (P < 0.05), sex (P < 0.05), and relocation (P < 0.01) caused significant differences in serum As, Pb, and Cd concentrations. A cluster analysis was carried out to classify the exposure pathways for target contaminants. The results indicated that 4 heavy metals in the serum of volunteers from northern China could be grouped into the same category, in which significant positive correlations were found between the serum heavy metal levels and background concentrations of surface soil. However, in other provinces and metropolises, the atmospheric pollution level played a critical role involving in the inhalation exposure pathway. We demonstrated that serum Pb levels in freshman students were related to the atmospheric transport and dry deposition of Pb.

WRF-Chem simulations of ozone pollution and control strategy in petrochemical industrialized and heavily polluted Lanzhou City, Northwestern China.

As the largest petrochemical industrialized city in northwestern China since the 1950s, Lanzhou has been well-known for its heavy surface ozone pollution. Given abundant emission sources of ozone precursors and the favorable environmental conditions for O3 formation, this study performed extensive atmospheric chemistry modeling investigations subject to 11 emission control scenarios. These scenarios increased and decreased emission levels of total volatile organic compound (TVOC) and nitrogen oxides (NOx), the two surface ozone (O3) precursor gases, to examine the relationships between O3 and NOx and TVOC. The modeling investigation was carried out for the summer of 2016 in the downtown and petrochemical industrial suburb in the city of Lanzhou. The results revealed that surface O3 in the downtown area of Lanzhou was controlled by VOCs and in the petrochemical-industrialized western suburb by NOx. Higher ozone levels were simulated in the west suburb of the city as compared with the downtown area, agreeing with measured data. The relationships between modeled TVOC/NOx ratios and O3 reductions, as well as the titration effect, were also discussed. The model results provided useful references for the mitigation strategy of ozone reduction in Lanzhou and other major cities in northwest China with similar climate and topography conditions.

[Pollution Characteristics, Dry Deposition Fluxes, and Sources for Atmospheric Polycyclic Aromatic Hydrocarbons in the Bosten Lake Watershed].

Passive air samplers (PAS-PUF) and passive dry deposition (PAS-DD) samplers were applied in the Bosten Lake watershed located in Xinjiang to estimate the atmospheric concentrations and dry deposition fluxes for 15 US EPA priority polycyclic aromatic hydrocarbons (PAHs) during a heating period in 2016 and no-heating period in 2017, respectively. The results showed that the atmospheric PAHs concentrations in the Bosten oasis area ranged from 6.38 ng·m-3 to 245.43 ng·m-3 during the heating period and 2.33 ng·m-3 to 74.76 ng·m-3 during the non-heating period. The highest atmospheric PAHs concentrations were found in the residential area, followed by regions near Bosten Lake and Tazhong. The atmospheric dry deposition fluxes of PAHs in the Bosten Lake watershed ranged from 0.45 µg·(m2·d)-1 to 18.10 µg·(m2·d)-1 during the heating period and 0.25 µg·(m2·d)-1to 8.15 µg·(m2·d)-1 during the non-heating period. During the heating period, the atmospheric dry deposition fluxes in the residential area were significantly higher than those in the regions near Bosten Lake and Tazhong. However, the atmospheric PAHs dry deposition flux in Tazhong was much higher than that in other sites during the heating and no-heating periods. In general, the atmospheric PAHs dry deposition fluxes during the heating period were significantly higher than those during the non-heating period. PAH composition for the atmosphere and dry deposition were dominated by 3 and 4 ring congeners, especially by phenanthrene, fluorine, fluoranthene, and pyrene during two sampling periods. In addition, the congener diagnostic ratio shows that coal and biomass combustion were possible sources of atmospheric PAHs in the Bosten Lake watershed. The forward and backward trajectory analysis based on the HYSPLIT model demonstrated that the higher atmospheric PAH emissions from the residential area would be transported to Bosten Lake, which can affect the aquatic environment of this lake by dry deposition.

[Pollution Characteristics and Occupational Exposure Risk of Heavy Metals in Indoor and Outdoor Ambient Particles at a Scaled Electronic Waste Dismantling Plant, Northwest China].

Atmospheric particle samples (PM1.0、PM2.5、PM10) were collected from three sampling sites (indoor and outdoor workplaces of a formal e-waste dismantling plant, and upwind area) in an arid area of Northwest China. The contents of six heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn) were analyzed using ICP-OES. Based on this data, the concentration levels, size distribution characteristics, and occupational exposure risks of heavy metals at the indoor and outdoor dismantling workplaces were studied. Particle analysis showed that Zn (4890 ng·m-3 indoors, 1245 ng·m-3 outdoors)、Pb (indoors 1201 ng·m-3, outdoors 240 ng·m-3), and Cu (indoors 1200 ng·m-3, outdoors 110 ng·m-3) showed higher pollution levels indoors and outdoors at the dismantling workplace. Moreover, the indoor concentration was much higher than that outdoors, indicating that the dismantling activity was the main cause of the high levels of heavy metal contamination. The indoor and outdoor air pollution characteristics were closely related to the types of electronic waste dismantled. Occupational exposure risk assessments showed that the total non-carcinogenic hazard quotient (HQ) of the indoor and outdoor dismantling workshops was 1.62×10-3, and 3.60×10-4, respectively, and the carcinogenic risk values were 2.69×10-7 and 2.59×10-9. Cd caused the greatest carcinogenic and non-carcinogenic risks at both indoor and outdoor dismantling workplaces, but it was still far below the limits (1.0) and acceptable ranges (1×10-6) stipulated by U.S. EPA, indicating that the health risks caused by heavy metals were minor or negligible. Heavy metals in the ambient particulate matter released from an adequately equipped and formally managed e-waste dismantling plant would not lead to any public health risk. The sedimentation characteristics of particulate heavy metals in different organs of the human respiratory system exhibited that the smaller the particle size was, the greater the proportion of deposition in the depths of the respiratory system was. Enterprises should make scientific and effective decisions on the respiratory health risks caused by such fine particles to the health of professional workers.