Volume therapy for cardiac arrest: a systematic review and meta-analysis.

Can PHOENICS resurrect hydroxyethyl starch? A cautious view.

The immunosuppressive tumor microenvironment and poor drug targeting remain major obstacles in bladder cancer (BC) therapy. To address this, a combination strategy integrating chemotherapy and immunotherapy was employed by co-delivering epirubicin (EPI) and the immune modulator imiquimod (IMQ) using a folate-modified nanocarrier. A hydroxyethyl starch-based epirubicin prodrug modified with folic acid (FA-HES-EPI) was first synthesized to improve tumor selectivity. FA-HES-EPI/IMQ micelles were then fabricated via nanoprecipitation by encapsulating IMQ into the hydrophobic core, aiming to achieve synergistic therapeutic efficacy. Folate modification conferred tumor-targeting capability to the micelles and promoted efficient cellular uptake via folate receptor-mediated endocytosis. The acid-sensitive hydrazone bond enabled controlled release of both EPI and IMQ in the acidic tumor microenvironment, thereby enhancing their combined chemo-immunotherapeutic effects. In an orthotopic BC model, FA-HES-EPI/IMQ micelles significantly enhanced drug accumulation at the tumor site, repolarized M2-type tumor-associated macrophages (TAMs) toward the M1 phenotype, remodeled the tumor stroma, and achieved a tumor inhibition rate of 96.7%, markedly surpassing that of FA-HES-EPI micelles (86.6%) and free EPI (62.3%), with negligible systemic toxicity. This pH-responsive co-delivery system represents a promising approach to improve both efficacy and safety in bladder cancer treatment.

The PHOENICS study: current evidence on the use of hydroxyethyl starch

Full-profile bioanalysis of polydisperse macromolecular hydroxyethyl starch 130/0.4 in rat plasma via LC-IS-CID coupled with MRM

To evaluate whether international decisions to withdraw medicines for safety, efficacy, or commercial reasons were reflected in the regulatory actions of Ecuador, Colombia, andPeru. A retrospective, descriptive, cross-sectional analysis identified active pharmaceutical ingredients (APIs) withdrawn globally by Stringent Regulatory Authorities (SRAs) between January 1, 2014, and June 30, 2025. Data were obtained from published SRA communications and verified in national regulatory databases-ARCSA (Ecuador), INVIMA (Colombia), and DIGEMID (Peru)-to determine current marketing status. APIs were categorized as never registered (no evidence in current or archival databases), previously registered (formally canceled/suspended with a safe of efficacy rationale), previously registered (authorization expired without an explicit safety rationale), or currently registered (active marketing authorization). Fifty-three APIs were withdrawn internationally, predominantly for safety concerns (69.81 %), followed by lack of efficacy (22.64 %) and manufacturer decisions (7.55 %). The European Medicines Agency issued most withdrawals, particularly for oncologic and hormonal agents. Despite these actions, Ecuador retained 16.98 % of withdrawn APIs on its market, Peru 7.55 %, and Colombia 7.55 %. Persisting products included modified-release paracetamol, hydroxyethyl starch, and ulipristal 5 mg-drugs associated with hepatotoxicity or fatal adverse events. Regulatory databases often list expired or active authorizations without public withdrawal notices. Substantial misalignment persists between international and Andean regulatory decisions. The continued regulatory authorization of withdrawn medicines highlights weaknesses in pharmacovigilance and transparency, underscoring the urgent need for regional harmonization and public disclosure of regulatory actions.

Video-assisted thoracic surgery (VATS) relies on one-lung ventilation (OLV) to achieve optimal surgical conditions. However, the lung protective ventilation strategies commonly employed during OLV diminish the accuracy of traditional dynamic parameters in predicting fluid responsiveness. The tidal volume challenge (TVC) has been proposed to overcome this limitation, yet its effectiveness in OLV patients remains to be validated. In this study, we used LiDCO to evaluate TVC-induced changes in SVV(ΔSVV_TVC) and PPV(ΔPPV_TVC), and assessed their ability to predict fluid responsiveness in patients receiving lung-protective OLV during VATS. All patients received OLV in lateral position after general anesthesia induction. Upon achieving hemodynamic stability, the study protocol was initiated. Hemodynamic and respiratory parameters, including heart rate, mean arterial pressure, stroke volume variation (SVV), pulse pressure variation (PPV), stroke volume index (SVI), cardiac index, peak inspiratory pressure, and dynamic lung compliance were recorded at four time points: before TVC (T1, tidal volume 6 mL/kg), 1min after TVC (T2, tidal volume 8 mL/kg), 2min after returning to baseline tidal volume (T3, pre-fluid challenge), and after volume loading test (VLT, T4). The VLT consisted of infusing 7 mL/kg hydroxyethyl starch over 20-30min. ΔSVV_TVC and ΔPPV_TVC were calculated as changes from T1 to T2, and the fluid responsiveness was defined as stroke volume index ≥ 10% increase after VLT. Among the 60 patients, 26 (43%) were fluid responders. ROC analysis showed that the area under the curve (AUC) of ΔSVV_TVC for predicting fluid responsiveness was 0.83 (95% CI, 0.71-0.91), with an optimal cutoff value of > 2%, sensitivity of 77%, specificity of 76%, and a gray zone range of 1%-3% encompassing 23 patients (38%). For ΔPPV_TVC, the AUC was 0.86 (95% CI, 0.74-0.93), with a cutoff of > 3%, sensitivity of 85%, specificity of 80%, and a gray zone of 2%-4% including 13 patients (22%).Subgroup analysis revealed no significant difference in the predictive AUC values of ΔSVV_TVC or ΔPPV_TVC between the left and right lateral decubitus positions. Tidal volume challenge -induced changes in SVV and PPV effectively predict fluid responsiveness in OLV patients, and their predictive performance is not influenced by patient position. This trial was registered with Chinese Clinical Trial Registry, ChiCTR2300075285, August 31, 2023.

Objective: This study aimed to compare the effects of hydroxyethyl starch (6% HES 130/0.4) administered as preload or coload on the incidence of maternal hypotension and neonatal outcomes in elective cesarean sections performed under spinal anesthesia.Methods: This prospective, randomized trial included 162 parturients aged 18–45 years with American Society of Anesthesiologists physical status II and a gestational age greater than 36 weeks undergoing elective cesarean delivery under spinal anesthesia. Participants received 500 mL of HES either 30 minutes before spinal anesthesia (preload group) or at the onset of cerebrospinal fluid flow (coload group). Maternal hemodynamic parameters were monitored throughout the procedure. Umbilical cord blood gas analysis, Apgar scores at 1 and 5 minutes, and total ephedrine consumption were recorded.Results: The incidence of maternal hypotension was 51.1% in the preload group and 48.9% in the coload group, with no statistically significant difference between groups (p = 0.83). Systolic arterial pressure at the onset of hypotension was 86.41 ± 8.63 mmHg in the preload group and 82.20 ± 9.14 mmHg in the coload group (p = 0.19). Total ephedrine requirement and umbilical cord blood gas parameters were comparable between groups. While 1-minute Apgar scores were similar, the 5-minute Apgar score was significantly higher in the preload group (p = 0.01).Conclusion: Colloid preload and coload administration were associated with comparable effects on maternal hypotension, vasopressor requirements, and neonatal outcomes in cesarean deliveries performed under spinal anesthesia.

Characterizing the cryobiological response of a mouse cardiac endothelial cell line to interrupted slow cooling (graded freezing).

BACKGROUNDThe choice of priming and volume replacement fluids during cardiopulmonary bypass (CPB) in cardiac surgery impacts hemodynamic stability, coagulation, renal function, and patient outcomes. Hydroxyethyl starch (HES) 130/0.4 and human albumin are commonly used colloids, but their relative safety and efficacy remain debated.AIMTo compare the outcomes of 6% HES 130/0.4 vs 5% albumin in patients undergoing cardiac surgery with CPB.METHODSA comprehensive literature search was performed in PubMed, EMBASE, ScienceDirect, and grey literature sources up to August 2025. Randomized controlled trials and controlled observational studies comparing 6% HES 130/0.4 with 5% albumin in patients who underwent cardiac surgery were included. Data extraction and risk of bias assessment followed PRISMA and Cochrane guidelines. Meta-analyses were conducted using RevMan 5.4, applying random-effects models. Heterogeneity was assessed with I2 statistics, and meta-regression explored baseline covariables. Publication bias was evaluated with funnel plots and the Egger’s test.RESULTSTwelve studies involving 908 patients (455 in the HES group, 453 in the albumin group) were included. No significant differences were observed between the HES and albumin groups for postoperative blood loss [mean difference = 42.4 mL, 95% confidence interval (CI): -90.0 to 174.9; P = 0.53], packed red blood cell transfusion [odds ratio (OR) = 0.78, 95%CI: 0.65-1.10; P = 0.16)], mortality (OR = 1.11, 95%CI: 0.63-1.96; P = 0.80), intensive care unit stay, hospital stay, or postoperative platelet count and creatinine levels. However, HES was associated with a significantly higher risk of acute kidney injury (AKI) (OR = 1.79, 95%CI: 1.08-2.97; P = 0.02), indicating that while many clinical outcomes showed no significant difference, there is a specific safety concern related to renal function with HES use. Meta-regression did not identify baseline factors explaining heterogeneity in bleeding or AKI outcomes (all P > 0.10). No significant publication bias was detected.CONCLUSIONThe 6% HES 130/0.4 and 5% albumin exhibit similar efficacy for volume management in cardiac surgery with CPB; however, HES is associated with a higher risk of AKI.

As an important anticoagulant molecule, antithrombin III (ATIII) has been confirmed to inhibit inflammation and to alleviate renal ischemia-reperfusion injury. The present study aimed to explore the relationship between serum ATIII level and acute kidney injury (AKI) in patients with traumatic brain injury (TBI). The clinical data of patients diagnosed with TBI and hospitalized in the West China Hospital (Chengdu, China) between January 2015 and June 2019 were collected. Logistic regression analysis was performed to analyze the relationship between ATIII and AKI and to construct predictive models. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the predictive value of ATIII and models were constructed. As a result, 203 patients with TBI were included in the present study. A total of 43 (19.7%) patients developed AKI at 24 h after admission. Compared with the non-AKI group, the AKI group had a lower Glasgow Coma Scale, injury severity score and ATIII, but had a higher glucose level, prothrombin time, levels of blood urea nitrogen and serum creatinine (SCr) and higher transfusion rate of fresh frozen plasma (FFP), red blood cell and hydroxyethyl starch. The mortality of the AKI group was 65.1%, which was higher compared with the 30.0% of the non-AKI group. SCr, ATIII and transfusion of FFP were independently associated with development of AKI after TBI. The AUC of the constructed three-factors predictive model was 0.850, which was higher compared with the AUC of 0.759 of only ATIII. Overall, ATIII was an effective predictive marker of AKI after TBI. Evaluating serum ATIII level and maintaining normal ATIII level may be beneficial for physicians to reduce the occurrence of AKI in patients with TBI.

Tailored iron oxide nanoparticles for biomedical applications: Hydroxyethyl starch coating enhances endothelial biocompatibility.

BackgroundIn an immunosuppressive microenvironment created by melanoma cells, interleukin (IL)-10 can promote tumor growth and impair the function of antigen-presenting cells, particularly dendritic cells. One of the leading strategies to counteract IL-10’s action is the administration of antibodies against its receptor. The tumor microenvironment can also be modulated by cytokines and/or cellular vaccines such as modified dendritic cells that overproduce IL-12, IL-15/IL-15Rα, and IL-18. These cellular vaccines serve as a source of cytokines and stimulate the immune system by presenting tumor antigens to lymphocytes. Furthermore, the efficacy of the dendritic cell vaccine can be achieved through the nanoconjugate of methotrexate and hydroxyethyl starch (HES-MTX), which reduces the activity of IL-10 and eliminates immunosuppressive cells.MethodsTwo experiments were conducted: one focusing on immunotherapy and the other on chemoimmunotherapy. The immunotherapy involved two administrations of cellular vaccines, preceded by anti-IL-10R antibody treatment. The chemoimmunotherapy additionally included a single administration of the HES-MTX nanoconjugate. The effectiveness of both therapies was evaluated through tumor growth inhibition measurements and analysis of lymphoid and myeloid cell populations in tumor tissues. Additionally, subpopulations of restimulated splenocytes were analyzed, and the production levels of interferon gamma (IFN-γ), IL-10, and IL-4 were evaluated.ResultsModified dendritic cells, which carry proinflammatory cytokines, were used in immuno- and chemoimmunotherapeutic experiments. The developed therapies effectively inhibited tumor growth, but the rate of tumor growth depended on the type of vaccine used. Incorporating the nanoconjugate prior to immunological treatment primarily reduced the population of suppressor cells. The most effective treatment was observed in two cases: as a result of immunotherapy including the use of a two-component vaccine DC/IL-12/TAg + DC/IL-18/TAg (TGI 62.3%) or after administration of HES-MTX nanoconjugate followed by immunotherapy with three-component vaccine - DC/IL-12/TAg + DC/IL-15/IL-15Rα/TAg + DC/IL-18/TAg (TGI 59.1%).

The optimal type of fluid for intraoperative fluid therapy remains uncertain and limited volumes of unbalanced crystalloids and hydroxyethyl starch appear to be safe in surgical patients. A mildly positive intraoperative fluid balance is generally recommended for patients having major non-cardiac surgery. Fluid responsiveness can help guide fluid administration, but should not be the only factor leading to fluid administration.

Saline versus balanced hydroxyethyl starch: does it matter? RETRACTION.

Intraoperative hydroxyethyl starch 130/0.4 infusion and graft function following donation-after-cardiac-death kidney transplantation

Interrupted slow cooling of mouse cardiac endothelial cell monolayers.

Background. Cells isolated from the testes of mammals and humans can be used for scientific purposes, maintaining certain animal lines and breeds, preserving biological material from endangered species, as well as in reproductive technologies. Most approaches for cryopreserving such cells utilize blood serum (or its derivatives) and dimethyl sulfoxide (DMSO). This can lead to unstable results, the spread of infections, altered expression of certain cell genes, and the manifestation of DMSO’s toxic effects. In our previous studies, serum-free media for testicular interstitial cells (ICs) were develo­ped; the aim of this work was to investigate their ability to synthesize testo­sterone after cryopreservation. Materials and Methods. ICs were obtained from mature rats via enzymatic digestion and cryopreserved in solutions containing 0.7 M DMSO and 100 mg/mL of one of the following polymers: dextran 40, hydroxyethyl starch, polyethylene oxide, or 1.4 M DMSO and 10% fetal bovine serum (FBS). The cooling rate was 1 °C/min. After cryopreservation, the cells were thawed in a water bath, the DMSO was removed, and their ability for basal and stimulated testosterone synthesis in vitro was assessed. Additionally, ICs were transplanted into castrated animals, and changes in free testosterone blood levels, seminal vesicle weight, and sexual behavior were examined. Results. The capacity for stimulated testosterone synthesis was preserved only in cells cryopreserved in the solution containing dextran 40 (0.7DMSO + D40) and FBS (1.4DMSO + FBS). Cryopreserved ICs enhanced sexual behavior parameters in castrated rats upon transplantation without removing the cryoprotective medium (0.7DMSO + D40), including mount and intromission latency, the mount and intromission frequency, ejaculation ability, and copulatory efficiency. Moreover, they helped maintain free testosterone blood levels and seminal vesicle weight in castrated animals after transplantation. Conclusions. It was demonstrated that ICs cryopreserved in the serum-free medium (0.7DMSO + D40) retained their ability to synthesize and secrete testosterone. Furthermore, the use of 0.7DMSO + D40 allows the immediate use of cells after thawing, bypassing the step of cryoprotectant removal, which could facilitate the translation of experimental protocols into practice.

BACKGROUNDHydroxyethyl starch (HES) is often used for maintaining vascular volume during major surgery. Long-term high-dose HES in septic patients promotes renal injury, whereas meta-analyses of current HES products in surgical patients do not show such effects.OBJECTIVEWe studied if the peri-operative use of HES is noninferior to crystalloids in terms of acute kidney injury. Secondary outcome was the noninferiority of HES on worsening of renal injury and/or the incidence of a composite endpoint of major complications and mortality until postoperative day 90.DESIGNRandomised double-blind trial in patients undergoing elective abdominal surgery with expected blood loss at least 500 ml.SETTINGMulticentre trial at 53 study sites in 10 European countries.PATIENTSOne thousand nine hundred and fifty-eight (HES 977, crystalloid-only 981) patients aged 40 to 85 years with ASA status II-III.INTERVENTIONEither 6% HES 130/0.4 or a crystalloid solution. Dosing was guided by mean arterial pressure and/or routine haemodynamic variables.MAIN OUTCOME MEASUREChange from pre-operative to lowest cystatin C-based eGFR during the first 3 postoperative days. Key secondary outcome was a composite endpoint of mortality and major postoperative complications after 90 days.RESULTSMean change in eGFR from baseline to minimum was -3.4 ± 17.7 ml min-1 1.73 m-2 in HES patients and -1.0 ± 17.1 ml min-11.73 m-2 in crystalloid-only patients (P < 0.001 for noninferiority). The key secondary endpoint occurred in 35% of patients in each group. There were no clinically relevant differences in any safety endpoint including 90-day renal function. Any cause mortality-difference until the end of 1-year follow-up was not significantly different (8.6% in HES and 10.1% in crystalloid patients).CONCLUSIONPeri-operative use of HES was noninferior to crystalloids in short-term renal function or a composite of mortality and major complications at 90 days. PHOENICS provides robust evidence that peri-operative in-label use of HES is well tolerated.TRIAL REGISTRATION AND FUNDINGEudraCT no. 2016-002162-30, clinicaltrials.gov ID NCT03278548.

Hemorrhage may suppress the amplitude of transcranial motor evoked potentials (TcMEPs). We compared the effects of hemorrhage, subsequent fluid resuscitation, and transient anesthetic deepening on the recently developed transesophageal motor evoked potentials (TeMEPs) with those on conventional TcMEPs. Twelve swine (26.0 ± 0.5kg) were anesthetized with 8-13% desflurane during preparation and then switched to propofol and remifentanil anesthesia. After baseline measurements, 700mL of blood was withdrawn over 30min to induce hypovolemia. Hypovolemia was then treated with 700mL of hydroxyethyl starch for 30min (fluid resuscitation). Subsequently, 5mg of remimazolam was administered, followed by 50mg of propofol after the effects of remimazolam had reversed. TcMEPs and TeMEPs were recorded at the end of each condition and immediately before and after the administration of remimazolam or propofol. In all conditions and in all limbs, TeMEPs' amplitudes were greater than those of TcMEPs. Massive hemorrhage reduced the amplitudes of both TeMEPs and TcMEPs in the bilateral lower limbs and this reduction was not reversed by fluid resuscitation. Following bolus administration of remimazolam or propofol, TcMEPs were markedly suppressed, whereas TeMEPs remained unchanged. Similar to TcMEPs, TeMEPs amplitudes may decrease after hemorrhage, and this suppression is not reversed by fluid resuscitation. However, unlike TcMEPs, TeMEPs are resistant to transient anesthetic deepening, suggesting that the observed suppression may be attributable to reduced oxygen delivery to the spinal cord rather than to anesthetic deepening.