BACKGROUND Accidental dural puncture(ADP)and subsequent post-dural puncture headache(PDPH)remain common complications of epidural procedures for obstetric anesthesia and analgesia.No clear consensus exists on the best...BACKGROUND Accidental dural puncture(ADP)and subsequent post-dural puncture headache(PDPH)remain common complications of epidural procedures for obstetric anesthesia and analgesia.No clear consensus exists on the best way to prevent PDPH after ADP.CASE SUMMARY We report our findings in twenty parturients who underwent an incorporated strategy of epidural analgesia followed by epidural hydroxyethyl starch(HES)to prevent PDPH after ADP with a 16-gauge Tuohy needle during epidural procedures.ADP with a 16-gauge Tuohy needle occurred in nine parturients undergoing a cesarean section(CS)and in eleven parturients receiving labor analgesia.An epidural catheter was re-sited at the same or adjacent intervertebral space in all patients.After CS,the epidural catheter was used for postoperative pain relief over a 48-h period.After delivery in eleven cases,epidural infusion was maintained for 24 h.Thereafter,15 mL of 6%HES 130/0.4 was administered via the epidural catheter immediately prior to catheter removal.None of the parturients developed PDPH or neurologic deficits over a follow-up period of at least two months to up to one year postpartum.CONCLUSION An incorporated strategy of epidural analgesia followed by epidural hydroxyethyl starch may have great efficacy in preventing PDPH after ADP.展开更多
The position and quantity of the hydroxyethyl groups in hydroxyethyl starch (HES) were studied by GC/MS and NMR. Quantitative characterization was carried out based on the results of both methods.
Photodynamic therapy(PDT)can produce high levels of reactive oxygen species(ROS)to kill tumor cells and induce antitumor immunity.However,intracellular antioxidant systems,including glutathione(GSH)system and thioredo...Photodynamic therapy(PDT)can produce high levels of reactive oxygen species(ROS)to kill tumor cells and induce antitumor immunity.However,intracellular antioxidant systems,including glutathione(GSH)system and thioredoxin(Trx)system,limit the accumulation of ROS,resulting in compromised PDT and insufficient immune stimulation.Herein,we designed a nanomedicine PtHPs co-loading photosensitizer pyropheophorbide a(PPa)and cisplatin prodrug Pt-COOH(Ⅳ)(Pt(Ⅳ))based on hydroxyethyl starch(HES)to inhibit both GSH and Trx antioxidant systems and achieve potent PDT as well as antitumor immune responses.Specifically,HES-PPa and HES-Pt were obtained by coupling HES with PPa and Pt(Ⅳ),and assembled into nanoparticle PtHPs by emulsification method to achieve the purpose of co-delivery of PPa and Pt(Ⅳ).PtHPs improved PPa photostability while retaining PPa photodynamic properties.In vitro experiments showed that PtHPs reduced GSH,inhibited Trx system and had better cell-killing effect and ROS generation ability.Subcutaneous tumormodels showed that PtHPs had good safety and tumor inhibition effect.Bilateral tumor models suggested that PtHPs promoted the release of damage-associated molecular patterns and the maturation of dendritic cells,induced T cell-mediated immune responses,and thus suppressed the growth of both primary and distal tumors.This study reports a novel platinum-based nanomedicine and provides a newstrategy for boosting PDT therapy-mediated antitumor immunity by overcoming intrinsic antioxidant systems.展开更多
Purpose: The primary aim of this study was to investigate volume effect and safety of up to 50 mL/kg BW 6% hydroxyethyl starch (HES) 130/0.4 in adult and pediatric patients undergoing major elective surgery. The need ...Purpose: The primary aim of this study was to investigate volume effect and safety of up to 50 mL/kg BW 6% hydroxyethyl starch (HES) 130/0.4 in adult and pediatric patients undergoing major elective surgery. The need to infuse human albumin may be reduced or avoided in Japan if these large doses 6% HES 130/0.4 can be infused. Methods: The study was an uncontrolled, open-labeled, multi-center trial. Fifteen adult and 5 pediatric patients undergoing major elective surgery received 6% HES 130/0.4 (Voluven®) with a maximum dose of 50 mL/kg from the start of surgery until 2 hours after the end of surgery according to a treatment algorithm. The primary efficacy endpoint was the volume effect of 6% HES 130/0.4 determined by the volume of saved albumin during the investigational period and the time course of hemodynamic stability in adult and pediatric patients. Safety parameters were fluid balance, hemodynamic and laboratory parameters ECG, local and systemic tolerance and adverse events. Results: Adult patients received a mean of 32.0 mL/kg of 6% HES 130/0.4. For 12 out of 15 adult patients an average amount of 1033.8 mL (18.6 mL/kg) albumin could be saved. The other 3 adult patients did not receive more than 1000 mL of HES 130/0.4. All pediatric patients received approximately 50 mL/kg of HES 130/0.4;for these patients an average amount of 39.9 mL/kg body weight albumin could be saved. The majority of adult patients, and all pediatric patients were hemodynamically stable at all 3 time points. The observed changes of the assessed laboratory parameters including hematological and coagulation parameters or in any other safety parameter determined did not reveal any safety concern related to the administration of 6% HES 130/0.4 up to doses of 50 mL/kg body weight. Conclusion: The study results indicate that 6% HES 130/0.4 has a reliable volume effect, could contribute to significant human albumin savings and was safe and well tolerated up to a maximum dose of 50 mL/kg body weight in adult and pediatric patients undergoing major elective surgery.展开更多
Background: In June 2013, the FDA issued a Black Box Warning on synthetic colloids resulting from data indicating an increased risk of mortality, renal injury, and excess bleeding incidence in septic patients admitted...Background: In June 2013, the FDA issued a Black Box Warning on synthetic colloids resulting from data indicating an increased risk of mortality, renal injury, and excess bleeding incidence in septic patients admitted to the Intensive Care Unit (ICU), and patients undergoing coronary artery bypass graft (CABG) surgery. The purpose of this study was to compare the incidence of mortality, incidence/severity of renal injury and bleeding in septic ICU patients, and patients undergoing CABG surgery who have received hydroxyethyl starch 130/0.4 or albumin. Methods: This was a retrospective, single center, cohort study conducted at a 433 bed tertiary care hospital in Lexington, Kentucky. Computer generated lists provided patients who received hydroxyethyl starch 130/0.4 or albumin during inpatient stay as either a sepsis patient in the ICU or post coronary artery bypass graft patient. All cause mortality was the primary endpoint and secondary endpoints included overall renal dysfunction, incidence of bleeding, and overall length of stay. Results: A total of 89 patients were evaluated that received albumin or hydroxyethyl starch 130/0.4 alone with either septic ICU or CABG diagnosis codes. There was no significant difference in all cause mortality (p = 0.64). Overall renal dysfunction showed no statistically significance between the two groups (p = 0.66). There was no statistically significant difference between the albumin or HES 130/0.4 arms with respect to bleeding (TIMI Minimal p = 0.57, TIMI Minor p = 0.69, TIMI Major p = 0.35). Patient who received albumin had a statistically significant longer hospital overall length of stay (p = 0.003). Conclusion: There was no difference between HES 130/0.4 and albumin in mortality, renal dysfunction, and bleeding in septic ICU and CABG patients. Patients receiving albumin had an increased overall length of stay. These findings suggest that hydroxyethyl starch 130/0.4 may be safe in the studied patient populations;however, further investigation into specific HES agents should be conducted.展开更多
Background The optimal colloid for use during kidney transplantation is not clear. Patients undergoing living-related kidney transplantation （LRKT） were used to compare the protective effects of 6% hydroxyethyl star...Background The optimal colloid for use during kidney transplantation is not clear. Patients undergoing living-related kidney transplantation （LRKT） were used to compare the protective effects of 6% hydroxyethyl starch 130/0.4 （HES 130/0.4） and 4% succinylated gelatine, as donor kidney procurement, ischemia time and surgical conditions are comparable. Stroke volume variation （SVV） was used to monitor intravascular volume to avoid renal allograft hypoperfusion.Methods Eighty patients undergoing LRKT were divided into two groups： group H received 6% HES 130/0.4 and group G received 4% succinylated gelatine. All donors and recipients received 15-25 ml/kg of the relevant colloid during surgery. Arterial blood pressure （ABP）, heart rate （HR）, central venous pressure （CVP）, SVV and cardiac index （CI）,electrocardiography （ECG） and SpO2 were monitored continuously. SVV was kept between 6%-13% and mean arterial pressure at 100-130 mmHg. Samples of venous blood and urine were obtained 30 minutes after unclamping and on the mornings of post-operative days （POD） 1-4 to measure serum and urine β2-microglobulin, urine α1-microglobulin,microalbumin and N-acetyl-β-D-glucosaminidase. Blood urea nitrogen （BUN） and creatine were determined pre-operation （to）, 3 hours after surgery （t1） and on PODs 1 （t2）, 2 （t3）, 4 （t4）, 7 （t5） and 10 （t6）. Urine output was recorded at t1, t2, t5, t6.Results Age, body weight, body surface area （BSA）, operation time, urine output and the colloid volume infused were comparable between the groups and hemodynamics were stable during surgery. BUN, serum creatine, serum β2-microglobulin and urine β2-microglobulin decreased significantly after surgery in both groups relative to the baseline.BUN decreased significantly in group H compared with group G at t1, t2 and t4. Urine microalbumin decreased significantly in group H on POD 4 compared with group G. Urine α1-microglobulin was not significantly different between the two groups.Conclusion Both colloids can be safely used for LRKT, but HES130/0.4 was associated with a more rapid recovery of renal function.展开更多
Background The effects of hydroxyethyl starch 130/0.4 （HES130/0.4） on myocardial ischemia/reperfusion （I/R） injury and its mechanism are uncertain.The aim of this study was to investigate the protective effects of...Background The effects of hydroxyethyl starch 130/0.4 （HES130/0.4） on myocardial ischemia/reperfusion （I/R） injury and its mechanism are uncertain.The aim of this study was to investigate the protective effects of HES 130/0.4 on myocardial I/R injury.Methods Forty-eight Sprague-Dawley rats were assigned to sham-operation group （S group）,ischemia-reperfusion group （I/R group）,albumin-I/R group （A-I/R group） and HES130/0.4-I/R group （H-I/R group）.The fluids were administered at 25 minutes after ischemia.H-I/R group was given 7.5 ml/kg of HES 130/0.4;I/R group and A-I/R group received the same volume of normal saline and 5% albumin,respectively.The rats in S group were sham operated and received the same fluid as I/R group.After 30 minutes of ischemia and 3 hours of reperfusion,blood samples were taken for cytokines assay,myocardium was excised for detection of NF-κB activity and myocardial infarction areas were taken for immunohistochemical analysis.Results Hemodynamic parameters of H-I/R group were better than I/R and A-I/R groups at all designated time points.The results of 2,3,5-triphenyl-tetrazolium（TTC） and HE staining were better in the H-I/R group.Myeloperoxidase （MPO）,NF-κB activity and concentrations of TNF-α,IL-1β were elevated markedly in I/R groups.HES130/0.4 lessened the release of TNF-α and IL-1β consistent with the reduction of MPO activity,and HES 130/0.4 inhibited the activity of NF-κB in H-I/R group.The number of apoptotic cells in the H-I/R group was also significantly reduced compared with I/R and A-I/R group Conclusion HES130/0.4 has a protective effect on I/R injured myocardium,probably by inhibiting NF-κB activity,reducing the release of pro-inflammatory cytokines and interfering with the apoptosis of cardiomyocytes.展开更多
Background： This meta-analysis was to determine the association of the cumulative dose of 130/0.4 or 0.42 （hydroxyethyl starch [HES] 130/0.4＊） or delta daily fluid balance （i.e., daily fluid balance in HES group ...Background： This meta-analysis was to determine the association of the cumulative dose of 130/0.4 or 0.42 （hydroxyethyl starch [HES] 130/0.4＊） or delta daily fluid balance （i.e., daily fluid balance in HES group over or below control group） with the heterogeneity of risk ratio （RR） for mortality in randomized control trials （RCTs）. Methods： Three databases （PubMed, EMBASE, Cochrane） were searched to identify prospective RCTs reporting mortality in adult patients with sepsis to compare HES 130/0.4＊ with crystalloids or albumin. Meta-analysis was performed using random effects. Sensitivity and meta-regression analyses were used to examine the heterogeneity sources of RR for mortality, Results： A total number of 4408 patients from 11 RCTs were included. The pooled RR showed no significant difference for overall mortality in patients with administration of liES130/0.4＂ compared with treatment of control fluids （RR： 1.02, 95% confidence interval： 0.9-1.17; P = 0.73）. Heterogeneity was moderate across recruited trials （l^2 = 34%, P = 0.13）. But, a significant variation was demonstrated in subgroup with crystalloids as control fluids （l^2 = 42%, P 〈 0.1）. Sensitivity analysis revealed that trials with high risk of bias did not significantly impact the pooled estimates for mortality. Meta-regression analysis also did not determine a dose-effect relationship of HES 130/0.4＊ with mortality （P - 0.298）, but suggested daily delta fluid balance being likely associated with mortality in septic patients receiving HES130/130/0.4＊ （P = 0.079）.Conclusions： Inappropriate daily positive fluid balance was likely an important source of heterogeneity in these trials reporting HES 130/0.4＊ associated with excess mortality in septic patients.展开更多
Cancer-associated fibroblasts(CAFs)play an important role in facilitating the progression of triple-negative breast cancer(TNBC)by deteriorating the tumor mechanical microenvironment(TMME).Herein,we designed a CAFs-ta...Cancer-associated fibroblasts(CAFs)play an important role in facilitating the progression of triple-negative breast cancer(TNBC)by deteriorating the tumor mechanical microenvironment(TMME).Herein,we designed a CAFs-targeting nanomedicine by conjugating doxorubicin(DOX)-loaded hydroxyethyl starch-IR780 nanoparticles(NPs)with Cys-Arg-Glu-Lys-Ala(CREKA)peptide,which had a special affinity for fibronectin overexpressed on CAFs.After systemic administration,the NPs efficiently targeted CAFs and generated hyperthermia upon light irradiation,decreasing CAFs through the combination of chemo-and photothermal-therapies.Thus,a series of changes in TMME were achieved by reducing CAFs,which further disrupted the niche of cancer stem cells(CSCs)to affect their survival.As a result,the tumor growth was significantly inhibited in 4T1 tumors.The strategy of TMME modulation and CSCs elimination through targeting and depleting CAFs provides a novel therapeutic treatment for desmoplastic solid tumors.展开更多
Objective To investigate the effectiveness of using a medium molecular weight hydroxyethyl starch solution (HES) administered as a replacement for estimated blood loss (EBL) during cytoreductive surgery for ovarian c...Objective To investigate the effectiveness of using a medium molecular weight hydroxyethyl starch solution (HES) administered as a replacement for estimated blood loss (EBL) during cytoreductive surgery for ovarian cancer on splanchnic oxygenation Methods Forty two patients undergoing cytoreductive surgery for ovarian cancer were enrolled in this prospective randomized study As soon as the EBL exceeded 10% but was less than 20% of the estimated blood volume, the patients were randomly assigned to receive either a volume of lactated Ringer's solution (LRS) equal to three times the EBL (LRS group, n=22) or a volume of 6% HES equal to the EBL (HES group, n=20) Tissue oxygenation was assessed indirectly by measuring tonometric parameters, including the difference between gastric intramucosal PsCO 2 and arterial PaCO 2 (Ps a CO 2 gap), gastric intramucosal pH (pHi) and arterial lactate acid concentration at 30 min after induction of anesthesia (baseline value), 1 hour and 2 hours after skin incision, and at the end of surgery Results At the end of surgery,the Ps a CO 2 gap in the HES group (8 7±1 6 mmHg) was significantly lower than that of the LRS group (18 74±4 4 mmHg, P <0 01), while the pHi (7 30±0 05 mmHg) in the HES group was significantly higher than that of the LRS group (7 21±0 07 mmHg, P <0 01) There was no significant difference between the two groups in terms of arterial lactate acid concentration Conclusion In patients undergoing major surgery with relatively large blood losses, volume resuscitation with medium molecular weight hydroxyethyl starch solution may improve splanchnic blood flow and tissue oxygenation展开更多
Many types of drugs and agents used for cancer diagnosis and therapy often have low bioavailability and insufficient efficacy,as well as causing various side effects due to their nonspecific delivery.Nanocarriers with...Many types of drugs and agents used for cancer diagnosis and therapy often have low bioavailability and insufficient efficacy,as well as causing various side effects due to their nonspecific delivery.Nanocarriers with purposely-designed compositions and structures have shown varying degrees of abilities to deliver these compounds towards cancers in passive or active manners.Despite the availability of a variety of materials for the construction of nanocarriers,natural polymers with good biocompatibility and biodegradability are preferable for such usage because of their high in vivo safety as well as easy removal of degradation products.Among the natural polymers intended for building nanocarriers,hydroxyethyl starch and its derivatives have gained tremendous attention in the field of drug delivery in the form of nanomedicines over the last decade.There is growing optimism that ever more hydroxyethyl starch-based nanomedicines will be a significant addition to the armoury currently used for cancer diagnosis and therapy.展开更多
Background:No convincing modalities have been shown to completely prevent postdural puncture headache(PDPH)after accidental dural puncture(ADP)during obstetric epidural procedures.We aimed to evaluate the role of epid...Background:No convincing modalities have been shown to completely prevent postdural puncture headache(PDPH)after accidental dural puncture(ADP)during obstetric epidural procedures.We aimed to evaluate the role of epidural administration of hydroxyethyl starch(HES)in preventing PDPH following ADP,regarding the prophylactic efficacy and side effects.Methods:Between January 2019 and February 2021,patients with a recognized ADP during epidural procedures for labor or cesarean delivery were retrospectively reviewed to evaluate the prophylactic strategies for the development of PDPH at a single tertiary hospital.The development of PDPH,severity and duration of headache,adverse events associated with prophylactic strategies,and hospital length of stay postpartum were reported.Results:A total of 105 patients experiencing ADP received a re-sited epidural catheter.For PDPH prophylaxis,46 patients solely received epidural analgesia,25 patients were administered epidural HES on epidural analgesia,and 34 patients received two doses of epidural HES on and after epidural analgesia,respectively.A significant difference was observed in the incidence of PDPH across the groups(epidural analgesia alone,31[67.4%];HES-Epidural analgesia,ten[40.0%];HES-Epidural analgesia-HES,five[14.7%];P<0.001).No neurologic deficits,including paresthesias and motor deficits related to prophylactic strategies,were reported from at least 2 months to up to more than 2 years after delivery.An overall backache rate related to HES administration was 10%.The multivariable regression analysis revealed that the HES-Epidural analgesia-HES strategy was significantly associated with reduced risk of PDPH following ADP(OR=0.030,95%confidence interval:0.006-0.143;P<0.001).Conclusions:The incorporated prophylactic strategy was associated with a great decrease in the risk of PDPH following obstetric ADP.This strategy consisted of re-siting an epidural catheter with continuous epidural analgesia and two doses of epidural HES,respectively,on and after epidural analgesia.The efficacy and safety profiles of this strategy have to be investigated further.展开更多
文摘BACKGROUND Accidental dural puncture(ADP)and subsequent post-dural puncture headache(PDPH)remain common complications of epidural procedures for obstetric anesthesia and analgesia.No clear consensus exists on the best way to prevent PDPH after ADP.CASE SUMMARY We report our findings in twenty parturients who underwent an incorporated strategy of epidural analgesia followed by epidural hydroxyethyl starch(HES)to prevent PDPH after ADP with a 16-gauge Tuohy needle during epidural procedures.ADP with a 16-gauge Tuohy needle occurred in nine parturients undergoing a cesarean section(CS)and in eleven parturients receiving labor analgesia.An epidural catheter was re-sited at the same or adjacent intervertebral space in all patients.After CS,the epidural catheter was used for postoperative pain relief over a 48-h period.After delivery in eleven cases,epidural infusion was maintained for 24 h.Thereafter,15 mL of 6%HES 130/0.4 was administered via the epidural catheter immediately prior to catheter removal.None of the parturients developed PDPH or neurologic deficits over a follow-up period of at least two months to up to one year postpartum.CONCLUSION An incorporated strategy of epidural analgesia followed by epidural hydroxyethyl starch may have great efficacy in preventing PDPH after ADP.
文摘The position and quantity of the hydroxyethyl groups in hydroxyethyl starch (HES) were studied by GC/MS and NMR. Quantitative characterization was carried out based on the results of both methods.
基金This work was financially supported by grants from the National Research and Development Program of China(2020YFA0211200,2020YFA0710700)the National Science Foundation of China(82172757)+2 种基金the Program for HUST Academic Frontier Youth Team(2018QYTD01)the HCP Program for HUSTthe Opening fund of Hubei Key Laboratory of Bioinorganic Chemistry&Materia Medica(No.BCMM202302).
文摘Photodynamic therapy(PDT)can produce high levels of reactive oxygen species(ROS)to kill tumor cells and induce antitumor immunity.However,intracellular antioxidant systems,including glutathione(GSH)system and thioredoxin(Trx)system,limit the accumulation of ROS,resulting in compromised PDT and insufficient immune stimulation.Herein,we designed a nanomedicine PtHPs co-loading photosensitizer pyropheophorbide a(PPa)and cisplatin prodrug Pt-COOH(Ⅳ)(Pt(Ⅳ))based on hydroxyethyl starch(HES)to inhibit both GSH and Trx antioxidant systems and achieve potent PDT as well as antitumor immune responses.Specifically,HES-PPa and HES-Pt were obtained by coupling HES with PPa and Pt(Ⅳ),and assembled into nanoparticle PtHPs by emulsification method to achieve the purpose of co-delivery of PPa and Pt(Ⅳ).PtHPs improved PPa photostability while retaining PPa photodynamic properties.In vitro experiments showed that PtHPs reduced GSH,inhibited Trx system and had better cell-killing effect and ROS generation ability.Subcutaneous tumormodels showed that PtHPs had good safety and tumor inhibition effect.Bilateral tumor models suggested that PtHPs promoted the release of damage-associated molecular patterns and the maturation of dendritic cells,induced T cell-mediated immune responses,and thus suppressed the growth of both primary and distal tumors.This study reports a novel platinum-based nanomedicine and provides a newstrategy for boosting PDT therapy-mediated antitumor immunity by overcoming intrinsic antioxidant systems.
文摘Purpose: The primary aim of this study was to investigate volume effect and safety of up to 50 mL/kg BW 6% hydroxyethyl starch (HES) 130/0.4 in adult and pediatric patients undergoing major elective surgery. The need to infuse human albumin may be reduced or avoided in Japan if these large doses 6% HES 130/0.4 can be infused. Methods: The study was an uncontrolled, open-labeled, multi-center trial. Fifteen adult and 5 pediatric patients undergoing major elective surgery received 6% HES 130/0.4 (Voluven®) with a maximum dose of 50 mL/kg from the start of surgery until 2 hours after the end of surgery according to a treatment algorithm. The primary efficacy endpoint was the volume effect of 6% HES 130/0.4 determined by the volume of saved albumin during the investigational period and the time course of hemodynamic stability in adult and pediatric patients. Safety parameters were fluid balance, hemodynamic and laboratory parameters ECG, local and systemic tolerance and adverse events. Results: Adult patients received a mean of 32.0 mL/kg of 6% HES 130/0.4. For 12 out of 15 adult patients an average amount of 1033.8 mL (18.6 mL/kg) albumin could be saved. The other 3 adult patients did not receive more than 1000 mL of HES 130/0.4. All pediatric patients received approximately 50 mL/kg of HES 130/0.4;for these patients an average amount of 39.9 mL/kg body weight albumin could be saved. The majority of adult patients, and all pediatric patients were hemodynamically stable at all 3 time points. The observed changes of the assessed laboratory parameters including hematological and coagulation parameters or in any other safety parameter determined did not reveal any safety concern related to the administration of 6% HES 130/0.4 up to doses of 50 mL/kg body weight. Conclusion: The study results indicate that 6% HES 130/0.4 has a reliable volume effect, could contribute to significant human albumin savings and was safe and well tolerated up to a maximum dose of 50 mL/kg body weight in adult and pediatric patients undergoing major elective surgery.
文摘Background: In June 2013, the FDA issued a Black Box Warning on synthetic colloids resulting from data indicating an increased risk of mortality, renal injury, and excess bleeding incidence in septic patients admitted to the Intensive Care Unit (ICU), and patients undergoing coronary artery bypass graft (CABG) surgery. The purpose of this study was to compare the incidence of mortality, incidence/severity of renal injury and bleeding in septic ICU patients, and patients undergoing CABG surgery who have received hydroxyethyl starch 130/0.4 or albumin. Methods: This was a retrospective, single center, cohort study conducted at a 433 bed tertiary care hospital in Lexington, Kentucky. Computer generated lists provided patients who received hydroxyethyl starch 130/0.4 or albumin during inpatient stay as either a sepsis patient in the ICU or post coronary artery bypass graft patient. All cause mortality was the primary endpoint and secondary endpoints included overall renal dysfunction, incidence of bleeding, and overall length of stay. Results: A total of 89 patients were evaluated that received albumin or hydroxyethyl starch 130/0.4 alone with either septic ICU or CABG diagnosis codes. There was no significant difference in all cause mortality (p = 0.64). Overall renal dysfunction showed no statistically significance between the two groups (p = 0.66). There was no statistically significant difference between the albumin or HES 130/0.4 arms with respect to bleeding (TIMI Minimal p = 0.57, TIMI Minor p = 0.69, TIMI Major p = 0.35). Patient who received albumin had a statistically significant longer hospital overall length of stay (p = 0.003). Conclusion: There was no difference between HES 130/0.4 and albumin in mortality, renal dysfunction, and bleeding in septic ICU and CABG patients. Patients receiving albumin had an increased overall length of stay. These findings suggest that hydroxyethyl starch 130/0.4 may be safe in the studied patient populations;however, further investigation into specific HES agents should be conducted.
文摘Background The optimal colloid for use during kidney transplantation is not clear. Patients undergoing living-related kidney transplantation （LRKT） were used to compare the protective effects of 6% hydroxyethyl starch 130/0.4 （HES 130/0.4） and 4% succinylated gelatine, as donor kidney procurement, ischemia time and surgical conditions are comparable. Stroke volume variation （SVV） was used to monitor intravascular volume to avoid renal allograft hypoperfusion.Methods Eighty patients undergoing LRKT were divided into two groups： group H received 6% HES 130/0.4 and group G received 4% succinylated gelatine. All donors and recipients received 15-25 ml/kg of the relevant colloid during surgery. Arterial blood pressure （ABP）, heart rate （HR）, central venous pressure （CVP）, SVV and cardiac index （CI）,electrocardiography （ECG） and SpO2 were monitored continuously. SVV was kept between 6%-13% and mean arterial pressure at 100-130 mmHg. Samples of venous blood and urine were obtained 30 minutes after unclamping and on the mornings of post-operative days （POD） 1-4 to measure serum and urine β2-microglobulin, urine α1-microglobulin,microalbumin and N-acetyl-β-D-glucosaminidase. Blood urea nitrogen （BUN） and creatine were determined pre-operation （to）, 3 hours after surgery （t1） and on PODs 1 （t2）, 2 （t3）, 4 （t4）, 7 （t5） and 10 （t6）. Urine output was recorded at t1, t2, t5, t6.Results Age, body weight, body surface area （BSA）, operation time, urine output and the colloid volume infused were comparable between the groups and hemodynamics were stable during surgery. BUN, serum creatine, serum β2-microglobulin and urine β2-microglobulin decreased significantly after surgery in both groups relative to the baseline.BUN decreased significantly in group H compared with group G at t1, t2 and t4. Urine microalbumin decreased significantly in group H on POD 4 compared with group G. Urine α1-microglobulin was not significantly different between the two groups.Conclusion Both colloids can be safely used for LRKT, but HES130/0.4 was associated with a more rapid recovery of renal function.
基金This work was supported by the grants from the Key Technologies R＆D Program of People＇s Liberation Army during the 11th Five-Year Plan Period （No. 08G071） and National Natural Science Foundation of China （No. 30772092）.Acknowledgements： We are grateful to CHEN Wen, for his help in statistical analysis.
文摘Background The effects of hydroxyethyl starch 130/0.4 （HES130/0.4） on myocardial ischemia/reperfusion （I/R） injury and its mechanism are uncertain.The aim of this study was to investigate the protective effects of HES 130/0.4 on myocardial I/R injury.Methods Forty-eight Sprague-Dawley rats were assigned to sham-operation group （S group）,ischemia-reperfusion group （I/R group）,albumin-I/R group （A-I/R group） and HES130/0.4-I/R group （H-I/R group）.The fluids were administered at 25 minutes after ischemia.H-I/R group was given 7.5 ml/kg of HES 130/0.4;I/R group and A-I/R group received the same volume of normal saline and 5% albumin,respectively.The rats in S group were sham operated and received the same fluid as I/R group.After 30 minutes of ischemia and 3 hours of reperfusion,blood samples were taken for cytokines assay,myocardium was excised for detection of NF-κB activity and myocardial infarction areas were taken for immunohistochemical analysis.Results Hemodynamic parameters of H-I/R group were better than I/R and A-I/R groups at all designated time points.The results of 2,3,5-triphenyl-tetrazolium（TTC） and HE staining were better in the H-I/R group.Myeloperoxidase （MPO）,NF-κB activity and concentrations of TNF-α,IL-1β were elevated markedly in I/R groups.HES130/0.4 lessened the release of TNF-α and IL-1β consistent with the reduction of MPO activity,and HES 130/0.4 inhibited the activity of NF-κB in H-I/R group.The number of apoptotic cells in the H-I/R group was also significantly reduced compared with I/R and A-I/R group Conclusion HES130/0.4 has a protective effect on I/R injured myocardium,probably by inhibiting NF-κB activity,reducing the release of pro-inflammatory cytokines and interfering with the apoptosis of cardiomyocytes.
文摘Background： This meta-analysis was to determine the association of the cumulative dose of 130/0.4 or 0.42 （hydroxyethyl starch [HES] 130/0.4＊） or delta daily fluid balance （i.e., daily fluid balance in HES group over or below control group） with the heterogeneity of risk ratio （RR） for mortality in randomized control trials （RCTs）. Methods： Three databases （PubMed, EMBASE, Cochrane） were searched to identify prospective RCTs reporting mortality in adult patients with sepsis to compare HES 130/0.4＊ with crystalloids or albumin. Meta-analysis was performed using random effects. Sensitivity and meta-regression analyses were used to examine the heterogeneity sources of RR for mortality, Results： A total number of 4408 patients from 11 RCTs were included. The pooled RR showed no significant difference for overall mortality in patients with administration of liES130/0.4＂ compared with treatment of control fluids （RR： 1.02, 95% confidence interval： 0.9-1.17; P = 0.73）. Heterogeneity was moderate across recruited trials （l^2 = 34%, P = 0.13）. But, a significant variation was demonstrated in subgroup with crystalloids as control fluids （l^2 = 42%, P 〈 0.1）. Sensitivity analysis revealed that trials with high risk of bias did not significantly impact the pooled estimates for mortality. Meta-regression analysis also did not determine a dose-effect relationship of HES 130/0.4＊ with mortality （P - 0.298）, but suggested daily delta fluid balance being likely associated with mortality in septic patients receiving HES130/130/0.4＊ （P = 0.079）.Conclusions： Inappropriate daily positive fluid balance was likely an important source of heterogeneity in these trials reporting HES 130/0.4＊ associated with excess mortality in septic patients.
基金the National Research and Development Program of China(Nos.2018YFA0208900,2020YFA0211200,and 2020YFA0710700)the National Natural Science Foundation of China(Nos.82172757 and 31972927)+2 种基金the Scientific Research Foundation of Huazhong University of Science and Technology(No.3004170130)the Program for HUST Academic Frontier Youth Team(No.2018QYTD01)the HCP Program for HUST.
文摘Cancer-associated fibroblasts(CAFs)play an important role in facilitating the progression of triple-negative breast cancer(TNBC)by deteriorating the tumor mechanical microenvironment(TMME).Herein,we designed a CAFs-targeting nanomedicine by conjugating doxorubicin(DOX)-loaded hydroxyethyl starch-IR780 nanoparticles(NPs)with Cys-Arg-Glu-Lys-Ala(CREKA)peptide,which had a special affinity for fibronectin overexpressed on CAFs.After systemic administration,the NPs efficiently targeted CAFs and generated hyperthermia upon light irradiation,decreasing CAFs through the combination of chemo-and photothermal-therapies.Thus,a series of changes in TMME were achieved by reducing CAFs,which further disrupted the niche of cancer stem cells(CSCs)to affect their survival.As a result,the tumor growth was significantly inhibited in 4T1 tumors.The strategy of TMME modulation and CSCs elimination through targeting and depleting CAFs provides a novel therapeutic treatment for desmoplastic solid tumors.
文摘Objective To investigate the effectiveness of using a medium molecular weight hydroxyethyl starch solution (HES) administered as a replacement for estimated blood loss (EBL) during cytoreductive surgery for ovarian cancer on splanchnic oxygenation Methods Forty two patients undergoing cytoreductive surgery for ovarian cancer were enrolled in this prospective randomized study As soon as the EBL exceeded 10% but was less than 20% of the estimated blood volume, the patients were randomly assigned to receive either a volume of lactated Ringer's solution (LRS) equal to three times the EBL (LRS group, n=22) or a volume of 6% HES equal to the EBL (HES group, n=20) Tissue oxygenation was assessed indirectly by measuring tonometric parameters, including the difference between gastric intramucosal PsCO 2 and arterial PaCO 2 (Ps a CO 2 gap), gastric intramucosal pH (pHi) and arterial lactate acid concentration at 30 min after induction of anesthesia (baseline value), 1 hour and 2 hours after skin incision, and at the end of surgery Results At the end of surgery,the Ps a CO 2 gap in the HES group (8 7±1 6 mmHg) was significantly lower than that of the LRS group (18 74±4 4 mmHg, P <0 01), while the pHi (7 30±0 05 mmHg) in the HES group was significantly higher than that of the LRS group (7 21±0 07 mmHg, P <0 01) There was no significant difference between the two groups in terms of arterial lactate acid concentration Conclusion In patients undergoing major surgery with relatively large blood losses, volume resuscitation with medium molecular weight hydroxyethyl starch solution may improve splanchnic blood flow and tissue oxygenation
基金This work was financially supported by the National Key Research and Development Program of China(No.2017YFC1103800).
文摘Many types of drugs and agents used for cancer diagnosis and therapy often have low bioavailability and insufficient efficacy,as well as causing various side effects due to their nonspecific delivery.Nanocarriers with purposely-designed compositions and structures have shown varying degrees of abilities to deliver these compounds towards cancers in passive or active manners.Despite the availability of a variety of materials for the construction of nanocarriers,natural polymers with good biocompatibility and biodegradability are preferable for such usage because of their high in vivo safety as well as easy removal of degradation products.Among the natural polymers intended for building nanocarriers,hydroxyethyl starch and its derivatives have gained tremendous attention in the field of drug delivery in the form of nanomedicines over the last decade.There is growing optimism that ever more hydroxyethyl starch-based nanomedicines will be a significant addition to the armoury currently used for cancer diagnosis and therapy.
文摘Background:No convincing modalities have been shown to completely prevent postdural puncture headache(PDPH)after accidental dural puncture(ADP)during obstetric epidural procedures.We aimed to evaluate the role of epidural administration of hydroxyethyl starch(HES)in preventing PDPH following ADP,regarding the prophylactic efficacy and side effects.Methods:Between January 2019 and February 2021,patients with a recognized ADP during epidural procedures for labor or cesarean delivery were retrospectively reviewed to evaluate the prophylactic strategies for the development of PDPH at a single tertiary hospital.The development of PDPH,severity and duration of headache,adverse events associated with prophylactic strategies,and hospital length of stay postpartum were reported.Results:A total of 105 patients experiencing ADP received a re-sited epidural catheter.For PDPH prophylaxis,46 patients solely received epidural analgesia,25 patients were administered epidural HES on epidural analgesia,and 34 patients received two doses of epidural HES on and after epidural analgesia,respectively.A significant difference was observed in the incidence of PDPH across the groups(epidural analgesia alone,31[67.4%];HES-Epidural analgesia,ten[40.0%];HES-Epidural analgesia-HES,five[14.7%];P<0.001).No neurologic deficits,including paresthesias and motor deficits related to prophylactic strategies,were reported from at least 2 months to up to more than 2 years after delivery.An overall backache rate related to HES administration was 10%.The multivariable regression analysis revealed that the HES-Epidural analgesia-HES strategy was significantly associated with reduced risk of PDPH following ADP(OR=0.030,95%confidence interval:0.006-0.143;P<0.001).Conclusions:The incorporated prophylactic strategy was associated with a great decrease in the risk of PDPH following obstetric ADP.This strategy consisted of re-siting an epidural catheter with continuous epidural analgesia and two doses of epidural HES,respectively,on and after epidural analgesia.The efficacy and safety profiles of this strategy have to be investigated further.
