Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on l...Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on large(> 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy(HAIC)might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX(mFOLFOX) regimen and those ofTACE in patients with massive unresectable HCC.Methods: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen(oxaliplatin, 85 mg/m^2 intra-arterial infusion; leucovorin,400 mg/m^2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m^2 continuous infusion)every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression(TTP), and safety were assessed.Results: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group(52.6% vs. 9.8%, P < 0.001;83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months(hazard radio[HR] = 2.35,95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection(10 vs. 3,P = 0.033). The proportions of grade 3-4 adverse events(AE) and serious adverse events(SAE) were lower in the HAIC group than in the TACE group(grade 3-4 AEs: 13 vs. 27, P = 0.007;SAEs: 6 vs. 15,p = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent(10 vs. 2,P = 0.026).Conclusions: HAIC with mFOLFOX yielded significantly bette展开更多
Background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. This study was conducted to determine the pharmacokinetics of TCI administered sufentanil in...Background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. This study was conducted to determine the pharmacokinetics of TCI administered sufentanil in Chinese surgical patients. Methods The pharmacokinetics of sufentanil was investigated in 12 adult patients, aged 23-76 years, scheduled for prolonged surgery under general anesthesia. Anesthetic induction was carried out with propofol, rocuronium and TCI administered sufentanil aiming for target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI lasted for 30 minutes. Frequent arterial blood samples （1.5 ml） were drawn during and up to 24 hours after sufentanil TCI. Plasma sufentanil concentrations were measured by liquid chromatography-tandem mass spectrometry; limit of sensitivity of mass spectrometry was 5 pg/ml. The data were analyzed with the nonlinear mixed-effect model program. Results The pharmacokinetics of TCI administered sufentanil were optimally described by a three-compartment model with the following parameters： the central volume of distribution （V1） = 5.4 L, the volume of distribution at steady-state （Vdss） = 195.4 L, systemic clearance （CI1） = 1.10 L/min, and elimination half-life （t1/2 Y） = 271.8 minutes. Both age and gender affected the pharmacokinetic parameters. The rapid distribution clearance （012） was negatively correlated with patient age, and the volume of slowly equilibrating compartment （V3） was positively correlated with age. The Cl2 and the volume of rapidly equilibrating compartment （V2） were influenced by gender with male patients showing higher values of Cl2 and V2 than female patients. There was no relationship of body weight, lean body mass, plasma albumin, or target effect-site concentration of sufentanil with any of the pharmacokinetic parameters studied. Conclusions The pharmacokinetics of TCI administered sufentanil in Chinese patients can be adequately described by a three-compartment model. Pharmacokinet展开更多
Background Sufentanil target controlled infusion （TCI） provides stable analgesia, better hemodynamic control than a bolus injection of intravenous anesthetics, anticipated recovery and improved quality of anesthesia...Background Sufentanil target controlled infusion （TCI） provides stable analgesia, better hemodynamic control than a bolus injection of intravenous anesthetics, anticipated recovery and improved quality of anesthesia during perioperative period. This study evaluated the accuracy and feasibility of TCI system for sufentanil at high concentrations in Chinese surgical patients. Methods Twelve low risk adult patients undergoing elective surgery under general anesthesia were included in this study. Sufentanil was administered with a specific TCI system incorporating the population pharmacokinetic data of sufentanil previously reported, using a target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI duration was 30 minutes. Frequent arterial blood samples were taken during and up to 24 hours after sufentanil TCI for determination of plasma sufentanil concentrations by liquid chromatography-mass spectrometry/mass spectrometry. The changes of circulatory system function during the procedure, recovery profile and adverse effects were recorded. Measured plasma sufentanil concentrations were compared with the values predicted by the TCI system. The bias （median performance error, MDPE）, precision （median absolute performance error, MDAPE） and wobble （variability of performance error） of the sufentanil TCI system were determined. Results All patients had stable cardiovascular variables during induction and maintenance of anesthesia. Time to eye opening and extubation were （5.6±1.7） minutes when TCI set to 4 ng/ml and （7.2±2.3） minutes when set to 6 ng/ml. There was no episode of agitation, muscle rigidity or intraoperative awareness. The bias （MDPE）, precision （MDAPE） and wobble of the sufentanil TCI system were -3.7%, 18.9% and 19.6% respectively during TCI, and the MDPE, MDAPE and wobble were -29.1%, 31.7% and 15.0% respectively after TCI （up to 8 hours）. Conclusions The TCI system programmed for sufentanil at 4 or 6 ng/ml was considered acceptable for clinical use i展开更多
Background There are few studies to assess whether the effect-site concentration of propofol can predict anesthetic depth during the target-controlled infusion （TCI） induction in elderly patients. This study aimed t...Background There are few studies to assess whether the effect-site concentration of propofol can predict anesthetic depth during the target-controlled infusion （TCI） induction in elderly patients. This study aimed to evaluate the relationship between effect-site concentration of propofol and depth of anesthesia during the TCI induction in elderly patients. Methods Ninety patients （60-80 years） with an American Society of Anesthesiologists （ASA） physical status of 1-3, undergoing scheduled abdominal and thoracic surgery under general anesthesia were randomly allocated into one of three groups, Group S1, S2 and S3 （30 patients in each group）. The patients in Group S1 received propofol with a target plasma concentration of 4.0 pg/ml; patients in Group S2 received propofol with an initial target plasma concentrations of 2.0 IJg/ml that was raised to 4.0 pg/ml 3 minutes later; patients in Group S3 received an infused scheme of 3 steps; starting from a target plasma concentration of 2.0 pg/ml that was increased stepwised by 1 pg/ml until a target plasma concentration of 4.0 pg/ml was achieved, the interval between the two steps was 3 minutes. When an Observer＇s Assessment of Alertness/Sedation （OANS） score of 1 was achieved, remifentanil （effect-site concentration （Ce） of 4.0 ng/ml） and rocuronium 0.9 mg/kg were administered. Tracheal intubation was started 2 minutes after rocuronium injection. Changes of propofol Ce, blood pressure （BP）, heart rate （HR）, and bispectral index （BIS） were recorded. Results When an OAA/S score of 1 was achieved, Ce of propofol were （1.7±0.4） pg/ml, （1.9±0.3） pg/ml, （1.9±0.4） pg/ml and the BIS values were 64±5, 65±8, and 62±8 in Groups S1, S2 and S3. Before intubation, Ce of propofol was （2.8±0.2） pg/ml, （2.8±0.3） pg/ml, （2.7±0.3） pg/ml, and the BIS values were 48±7, 51±7, and 47±5 in Groups S1, S2 and S3. By linear regression analysis, a significant correlation between Ce of propofol and BIS values was found （展开更多
No effective drug treatments are available for coronavirus disease 2019(COVID-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functi...No effective drug treatments are available for coronavirus disease 2019(COVID-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functional disability in survivors require clinical evaluation.We performed a parallel assigned controlled,non-randomized,phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells(UC-MSCs)infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease.The study enrolled 18 hospitalized patients with COVID-19(n=9 for each group).The treatment group received three cycles of intravenous infusion of UC-MSCs(3×107 cells per infusion)on days 0,3,and 6.Both groups received standard COVID-treatment regimens.Adverse events,duration of clinical symptoms,laboratory parameters,length of hospitalization,serial chest computed tomography(CT)images,the PaO2/FiO2 ratio,dynamics of cytokines,and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed.No serious UC-MSCs infusion-associated adverse events were observed.Two patients receiving UC-MSCs developed transient facial flushing and fever,and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion.Mechanical ventilation was required in one patient in the treatment group compared with four in the control group.All patients recovered and were discharged.Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated.Phase 2/3 randomized,controlled,double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.展开更多
基金supported by the National Natural Science Foundation of China(No.81625017 and No.81572385)the Fundamental Research Funds for the Central Universities of China(No.16ykjc36)
文摘Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on large(> 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy(HAIC)might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX(mFOLFOX) regimen and those ofTACE in patients with massive unresectable HCC.Methods: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen(oxaliplatin, 85 mg/m^2 intra-arterial infusion; leucovorin,400 mg/m^2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m^2 continuous infusion)every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression(TTP), and safety were assessed.Results: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group(52.6% vs. 9.8%, P < 0.001;83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months(hazard radio[HR] = 2.35,95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection(10 vs. 3,P = 0.033). The proportions of grade 3-4 adverse events(AE) and serious adverse events(SAE) were lower in the HAIC group than in the TACE group(grade 3-4 AEs: 13 vs. 27, P = 0.007;SAEs: 6 vs. 15,p = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent(10 vs. 2,P = 0.026).Conclusions: HAIC with mFOLFOX yielded significantly bette
文摘Background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. This study was conducted to determine the pharmacokinetics of TCI administered sufentanil in Chinese surgical patients. Methods The pharmacokinetics of sufentanil was investigated in 12 adult patients, aged 23-76 years, scheduled for prolonged surgery under general anesthesia. Anesthetic induction was carried out with propofol, rocuronium and TCI administered sufentanil aiming for target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI lasted for 30 minutes. Frequent arterial blood samples （1.5 ml） were drawn during and up to 24 hours after sufentanil TCI. Plasma sufentanil concentrations were measured by liquid chromatography-tandem mass spectrometry; limit of sensitivity of mass spectrometry was 5 pg/ml. The data were analyzed with the nonlinear mixed-effect model program. Results The pharmacokinetics of TCI administered sufentanil were optimally described by a three-compartment model with the following parameters： the central volume of distribution （V1） = 5.4 L, the volume of distribution at steady-state （Vdss） = 195.4 L, systemic clearance （CI1） = 1.10 L/min, and elimination half-life （t1/2 Y） = 271.8 minutes. Both age and gender affected the pharmacokinetic parameters. The rapid distribution clearance （012） was negatively correlated with patient age, and the volume of slowly equilibrating compartment （V3） was positively correlated with age. The Cl2 and the volume of rapidly equilibrating compartment （V2） were influenced by gender with male patients showing higher values of Cl2 and V2 than female patients. There was no relationship of body weight, lean body mass, plasma albumin, or target effect-site concentration of sufentanil with any of the pharmacokinetic parameters studied. Conclusions The pharmacokinetics of TCI administered sufentanil in Chinese patients can be adequately described by a three-compartment model. Pharmacokinet
文摘Background Sufentanil target controlled infusion （TCI） provides stable analgesia, better hemodynamic control than a bolus injection of intravenous anesthetics, anticipated recovery and improved quality of anesthesia during perioperative period. This study evaluated the accuracy and feasibility of TCI system for sufentanil at high concentrations in Chinese surgical patients. Methods Twelve low risk adult patients undergoing elective surgery under general anesthesia were included in this study. Sufentanil was administered with a specific TCI system incorporating the population pharmacokinetic data of sufentanil previously reported, using a target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI duration was 30 minutes. Frequent arterial blood samples were taken during and up to 24 hours after sufentanil TCI for determination of plasma sufentanil concentrations by liquid chromatography-mass spectrometry/mass spectrometry. The changes of circulatory system function during the procedure, recovery profile and adverse effects were recorded. Measured plasma sufentanil concentrations were compared with the values predicted by the TCI system. The bias （median performance error, MDPE）, precision （median absolute performance error, MDAPE） and wobble （variability of performance error） of the sufentanil TCI system were determined. Results All patients had stable cardiovascular variables during induction and maintenance of anesthesia. Time to eye opening and extubation were （5.6±1.7） minutes when TCI set to 4 ng/ml and （7.2±2.3） minutes when set to 6 ng/ml. There was no episode of agitation, muscle rigidity or intraoperative awareness. The bias （MDPE）, precision （MDAPE） and wobble of the sufentanil TCI system were -3.7%, 18.9% and 19.6% respectively during TCI, and the MDPE, MDAPE and wobble were -29.1%, 31.7% and 15.0% respectively after TCI （up to 8 hours）. Conclusions The TCI system programmed for sufentanil at 4 or 6 ng/ml was considered acceptable for clinical use i
文摘Background There are few studies to assess whether the effect-site concentration of propofol can predict anesthetic depth during the target-controlled infusion （TCI） induction in elderly patients. This study aimed to evaluate the relationship between effect-site concentration of propofol and depth of anesthesia during the TCI induction in elderly patients. Methods Ninety patients （60-80 years） with an American Society of Anesthesiologists （ASA） physical status of 1-3, undergoing scheduled abdominal and thoracic surgery under general anesthesia were randomly allocated into one of three groups, Group S1, S2 and S3 （30 patients in each group）. The patients in Group S1 received propofol with a target plasma concentration of 4.0 pg/ml; patients in Group S2 received propofol with an initial target plasma concentrations of 2.0 IJg/ml that was raised to 4.0 pg/ml 3 minutes later; patients in Group S3 received an infused scheme of 3 steps; starting from a target plasma concentration of 2.0 pg/ml that was increased stepwised by 1 pg/ml until a target plasma concentration of 4.0 pg/ml was achieved, the interval between the two steps was 3 minutes. When an Observer＇s Assessment of Alertness/Sedation （OANS） score of 1 was achieved, remifentanil （effect-site concentration （Ce） of 4.0 ng/ml） and rocuronium 0.9 mg/kg were administered. Tracheal intubation was started 2 minutes after rocuronium injection. Changes of propofol Ce, blood pressure （BP）, heart rate （HR）, and bispectral index （BIS） were recorded. Results When an OAA/S score of 1 was achieved, Ce of propofol were （1.7±0.4） pg/ml, （1.9±0.3） pg/ml, （1.9±0.4） pg/ml and the BIS values were 64±5, 65±8, and 62±8 in Groups S1, S2 and S3. Before intubation, Ce of propofol was （2.8±0.2） pg/ml, （2.8±0.3） pg/ml, （2.7±0.3） pg/ml, and the BIS values were 48±7, 51±7, and 47±5 in Groups S1, S2 and S3. By linear regression analysis, a significant correlation between Ce of propofol and BIS values was found （
基金supported by The National Key R&D Program of China(2020YFC0841900,2020YFC0844000)The Innovation Groups of the National Natural Science Foundation of China(81721002)+2 种基金The National Science and Technology Major Project(2017YFA0105703)The Military Emergency Research Project for COVID-19(BWS20J006)The Project for Innovation of Military Medicine of China(16CXZ045).
文摘No effective drug treatments are available for coronavirus disease 2019(COVID-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functional disability in survivors require clinical evaluation.We performed a parallel assigned controlled,non-randomized,phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells(UC-MSCs)infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease.The study enrolled 18 hospitalized patients with COVID-19(n=9 for each group).The treatment group received three cycles of intravenous infusion of UC-MSCs(3×107 cells per infusion)on days 0,3,and 6.Both groups received standard COVID-treatment regimens.Adverse events,duration of clinical symptoms,laboratory parameters,length of hospitalization,serial chest computed tomography(CT)images,the PaO2/FiO2 ratio,dynamics of cytokines,and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed.No serious UC-MSCs infusion-associated adverse events were observed.Two patients receiving UC-MSCs developed transient facial flushing and fever,and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion.Mechanical ventilation was required in one patient in the treatment group compared with four in the control group.All patients recovered and were discharged.Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated.Phase 2/3 randomized,controlled,double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.
