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Low-molecular weight heparin (LMWH) has been the standard of care for treatment of venous thromboembolism (VTE) in patients with cancer. Rivaroxaban was approved in 2012 for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), but no prior studies have been reported specifically evaluating the efficacy and safety of rivaroxaban for cancer-associated thrombosis (CAT). Under a Quality Assessment Initiative (QAI), we established a Clinical Pathway to guide rivaroxaban use for CAT and now report a validation analysis of our first 200 patients. A 200 patient cohort with CAT (PE or symptomatic, proximal DVT), whose full course of anticoagulation was with rivaroxaban, were accrued. In competing risk analysis, primary endpoints at 6 months included new or recurrent PE or symptomatic proximal lower extremity DVT, major bleeding, clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban, or death. In competing risk analysis, the 6 months cumulative incidence of new or recurrent VTE was 4.4 % (95 % CI = 1.4–7.4 %), major bleeding was 2.2 % (95 % CI = 0−4.2 %) and all-cause mortality 17.6 % (95 % CI = 11.7–23.0 %). In this cohort of 200 patients with active cancer and CAT the rates of new or recurrent VTE and major bleeding were comparable to the cancer subgroup analysis from the EINSTEIN studies. The results of our Clinical Pathway provide guidance on Rivaroxaban use for treatment of CAT, and suggest that safety and efficacy is preserved, compared with past-published experience with LMWH.

Low‐molecular‐weight heparin has been the preferred treatment of cancer‐associated thrombosis (CAT); however, emerging data support the use of direct oral anticoagulants (DOACs). The Memorial Sloan Kettering Cancer Center Clinical Pathway has served as the institutional guideline for the use of rivaroxaban to treat CAT since 2014. Key elements are to recommend against use of a DOAC in patients with active gastrointestinal (GI) or genitourinary tract lesions, and a prespecified dose reduction in the elderly (75+ years old). We present our institutional experience for treatment of CAT. From January 2014 through September 2016, 1072 patients began rivaroxaban treatment for CAT; 91.9% had a solid tumor, 8.1% had hematologic malignancies, and 75% of patients with solid tumors had metastatic disease. All patients with CAT treated with rivaroxaban were included in this analysis, regardless of adherence to the Clinical Pathway. The 6‐month cumulative incidence of recurrent venous thromboembolism and major bleeding were 4.2% (95% confidence interval [CI], 2.7%‐5.7%) and 2.2% (95% CI, 1.1%‐3.2%), respectively. The incidence of clinically relevant non–major bleeding leading to discontinuation of rivaroxaban for at least 7 days was 5.5% (95% CI,  3.7%‐7.1%), and 73.3% of major bleeds occurred in the GI tract. The 6‐month cumulative mortality rate was 22.2% (95% CI, 19.4%‐24.9%). The elderly had similar rates of recurrent thrombosis and bleeding as those aged under 75 years. Our institutional experience suggests that in appropriately selected patients, rivaroxaban may be used for treatment of CAT with promising safety and efficacy.

Abstract Rivaroxaban is broadly used for the primary prevention of stroke and systemic embolism in the general population with non-valvular atrial fibrillation (AF). However, there is little published evidence on the safety and efficacy of rivaroxaban for AF in patients with active cancer. The aim of this study was to assess the safety and efficacy of rivaroxaban in patients with active cancer and AF. Use of rivaroxaban in cancer patients at Memorial Sloan Kettering Cancer Center (MSKCC) is monitored in the setting of a Quality Assessment Initiative. Patients with active cancer and AF, treated with rivaroxaban from 1/1/2014 through 3/31/2016 are included in this analysis. Clinical endpoints were defined a priori and assessed through text searches of medical records. A total of 163 evaluable patients were identified. After adjusting for competing risks, the estimated 1 year cumulative incidence of ischemic stroke was 1.4% (95% CI=0-3.4%) and major bleeding was 1.2% (95% CI=0-2.9%). The risk of clinically-relevant non-major bleeding leading to discontinuation of anticoagulation at 1 year was 14.0% (95% CI=4.2-22.7%). The cumulative incidence of mortality was 22.6% (95% CI=12.2-31.7%) at one year, reflecting an active cancer population. One patient died after developing an acute ischemic cerebrovascular insult. In conclusion, the safety and efficacy of rivaroxaban treatment for non-valvular AF in patients with active cancer is comparable to the results of the ROCKET-AF study in the general population.

The development of thrombocytopenia in the setting of therapeutic anticoagulation for venous thromboembolic disease (VTE) is common in cancer patients, but guidelines for management are based on limited past data and have not been validated. In 2011, Memorial Sloan Kettering Cancer Center (MSKCC) implemented the following guidelines in this setting: administer full dose enoxaparin for a platelet count > 50,000/mcL, half-dose enoxaparin for a platelet count of 25,000–50,000/mcL, and hold anticoagulation for a platelet count < 25,000/mcL. We now report validation of safety and efficacy of these guidelines. As a Quality Assessment Initiative, we evaluated our guidelines for adult cancer patients at MSKCC who were on therapeutic-dose enoxaparin for VTE during the years 2011 through 2013 and experienced at least one 7-day period of thrombocytopenia (platelet count ≤ 50,000/mcL). We assessed adherence to the enoxaparin dose modification guidelines, major bleeding, clinically relevant non-major bleeding, recurrent VTE, and mortality during the thrombocytopenic episodes. We identified 99 patients with 140 episodes of thrombocytopenia of 7 or more days. The median duration of these thrombocytopenic episodes was 12 days. The enoxaparin dose was modified in 133 of the 140 episodes (95%), reflecting satisfactory adherence to our institutional guidelines. There were no recurrent VTE events or major bleeding episodes when the anticoagulant dose was reduced or held. In this cohort, there was only one major bleeding episode, a trauma-associated retroperitoneal hemorrhage that occurred on the third day of a thrombocytopenic episode, prior to enoxaparin dose modification. There were 13 clinically relevant non-major bleeding episodes. Lastly, 10 patients died of cancer-related causes during an episode of thrombocytopenia. This Quality Assessment Initiative supports the safety and efficacy of our guidelines for therapeutic enoxaparin dose modification.

Rivaroxaban is broadly used for the primary prevention of stroke and systemic embolism in the general population with nonvalvular atrial fibrillation (AF). However, there is little published evidence on the safety and efficacy of rivaroxaban for AF in patients with active cancer. The aim of this study was to assess the safety and efficacy of rivaroxaban in patients with active cancer and AF. The use of rivaroxaban in patients with cancer at the Memorial Sloan Kettering Cancer Center is monitored in the setting of a Quality Assessment Initiative. Patients with active cancer and AF, treated with rivaroxaban from January 1, 2014, to March 31, 2016, are included in this analysis. Clinical end points were defined a priori and assessed through text searches of medical records. A total of 163 evaluable patients were identified. After adjusting for competing risks, the estimated 1-year cumulative incidence of ischemic stroke was 1.4% (95% CI 0% to 3.4%) and major bleeding was 1.2% (95% CI 0% to 2.9%). The risk of clinically relevant nonmajor bleeding leading to discontinuation of anticoagulation at 1 year was 14.0% (95% CI 4.2% to 22.7%). The cumulative incidence of mortality was 22.6% (95% CI 12.2% to 31.7%) at 1 year, reflecting an active cancer population. One patient died after developing an acute ischemic cerebrovascular insult. In conclusion, the safety and efficacy of rivaroxaban treatment for nonvalvular AF in patients with active cancer is comparable to the results of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) study in the general population.

Soil heavy metal contaminated sites with multiple sources of pollution have caused worldwide public concern. However, the lack of correlation of risk assessment between source identification of heavy metal leads to unclear direction of source governance. An integrated methodology is established in this study by combining source apportionment and human health risks model to characterize source-identified risks of heavy metals based on spatial interplotation. Principal component analysis and positive matrix factorization model are used to identify and classify potential sources of heavy metals synthetically. The integrated results are incorporated into the health risk model to evaluate potential non-carcinogenic and carcinogenic risk of soil heavy metals. A case study was conducted in Suzhou city of China. The results indicate that concentrations of Cd and Hg were highly above the background values, accounting for percentages of 239.6% and 415.9% above background values, respectively. The source-contributed human health risk index of As contributed 76.9% to non-carcinogenic risk by pollutant sources of agriculture activities. The non-carcinogenic health risk index for adults and children are 0.308 and 1.00 respectively, indicating health threat to the children. Overall, the non-carcinogenic and carcinogenic risks of heavy metals are at an unacceptable level of risk and require environmental management. Furthermore, the health risk evaluation based on source contribution suggests that industrial processes contribute more to the health risk of heavy metals in soils. This study will provide a new insight for the treatment of mutil-sources of soil heavy metal pollution and also some reference value for the improvement of the risk assessment system.

The pH-responsive hydrogels were obtained through successive carboxymethylation and phosphorylase elongatation of phytoglycogen and their structure and functional characterizations were investigated. Phytoglycogen (PG) was first carboxymethylated to obtain carboxymethyl phytoglycogen (CM-PG) with degree of substitution (DS) at 0.15, 0.25, 0.30, and 0.40, respectively. Iodine staining and X-ray diffraction analysis suggested that the linear glucan chains were successfully phosphorylase-elongated from the non-reducing ends at the CM-PG surface and assembled into the double helical segments, leading to formation of the hydrogel. The DS of CM-PG significantly influenced elongation of glucan chains. Specifically, fewer glucan chains were elongated for CM-PG with higher DS and the final glucan chains were shorter, resulting in lower gelation rate of chain-elongated CM-PG and lower firmness of the corresponding hydrogels. Scanning electron microscope observed that the hydrogels exhibited a porous and interconnected morphology. The swelling ratio and volume of hydrogels was low at pH 3–5 and then became larger at pH 6–8 due to electrostatic repulsion resulting from deprotonated carboxymethyl groups. Particularly, the hydrogel prepared from chain-elongated CM-PG (DS = 0.25) showed the highest sensitivity to pH. These results suggested that phosphorylase-treated CM-PG formed the pH-responsive hydrogel and that the elongation degree and the properties of hydrogels depended on the carboxymethylation degree. Thus, it was inferred that these hydrogels was a potential carrier system of bioactive substances for their targeted releasing in small intestine.

Postoperative pain after open hepatectomy is significant. Preoperative coagulopathy limits the use of epidural analgesia, the gold standard for pain control in open abdominal surgery. Erector spinae plane block (ESPB) is a novel regional anesthesia technique that has been shown to provide effective analgesia in abdominal surgery. In this study, we compared the analgesic efficacy of patient-controlled continuous ESPB (CESPB) with hydromorphone patient-controlled intravenous analgesia (PCIA) after right subcostal incision hepatectomies in hepatocellular carcinoma patients with preoperative coagulopathy. In this randomized, controlled, unblinded, and noninferiority trial, 120 patients were randomized to receive either CESPB or PCIA as primary postoperative analgesia together with parecoxib (40mg Q12 h IV) for 3 days after surgery. The primary outcome was the average cough-elicited pain numeric rating scales (NRS) recorded at the seven follow-up time points of 20:00 on the day of surgery and 9:00 and 15:00 on the postoperative day 1 to day 3 (POD1 to POD3). The average cough-elicited pain NRS score was 2.402 in the CESPB group and 2.676 in the PCIA group. The mean difference (95% CI) was -0.274 (-0.620 to 0.072), which demonstrated the noninferiority of CESPB to PCIA. Patients in the CESPB group had less intraoperative opioid consumption, a lower incidence of moderate-to-severe pain and PONV at POD3, and early resumption of oral intake. CESPB provides analgesic efficacy noninferior to opioid PCIA in the context of multimodal analgesia after right subcostal incision open hepatectomy.

Rapid sequence induction and intubation (RSII) requires an agent that provides excellent intubating conditions with minimal hemodynamic disturbance. Propofol is standard but often causes hypotension. We compared the novel agent ciprofol with propofol for RSII in adult patients scheduled for elective non-cardiac surgery. In this prospective, randomized, double-blind, non-inferiority trial, 170 adult patients scheduled for elective non-cardiac surgery were allocated to receive intravenous ciprofol (0.4 mg/kg, n = 85) or propofol (2.0 mg/kg, n = 85) for induction, with remifentanil and rocuronium. The non-inferiority margin was set at -10% for the primary outcome. The primary outcome was the proportion of patients with excellent intubation conditions (Viby-Mogensen scale). Secondary outcomes included incidence of hypotension, induction success rate, time to loss of consciousness (LOC), bispectral index (BIS) values, and pain on injection. Excellent intubation conditions were achieved in 96.5% (82/85) of the ciprofol group and 95.3% (81/85) of the propofol group (difference 1.2%, 95% CI: -4.4% to 6.7%). The lower limit of the 95% CI exceeded the prespecified non-inferiority margin of -10%. The per-protocol analysis confirmed non-inferiority (difference 1.2%, 95% CI -4.2% to 6.7%). The incidence of post-induction hypotension was significantly lower in the ciprofol group (15.3% vs 43.5%; RR 0.35, 95% CI 0.20 to 0.61; P < 0.001). No patient reported injection pain with ciprofol, compared to 68.2% with propofol (P < 0.001). Time to LOC and induction success rates were similar between groups. In adult patients undergoing elective non-cardiac surgery under a standardized RSI protocol, ciprofol 0.4 mg/kg provided intubating conditions non-inferior to propofol 2.0 mg/kg and was associated with less post-induction hypotension and injection pain. Further studies are needed in emergency, critically ill, and high-risk RSI populations. Chinese Clinical Trial Registry (ChiCTR2500095742).