Efficacy and safety of propofol target-controlled infusion combined with butorphanol for sedated colonoscopy

BACKGROUND Propofol is a short-acting,rapid-recovering anesthetic widely used in sedated colonoscopy for the early detection,diagnosis and treatment of colon diseases.However,the use of propofol alone may require high doses to achieve the induction of anesthesia in sedated colonoscopy,which has been associated with anesthesia-related adverse events(AEs),including hypoxemia,sinus bradycardia,and hypotension.Therefore,propofol co-administrated with other anesthetics has been proposed to reduce the required dose of propofol,enhance the efficacy,and improve the satisfaction of patients receiving colonoscopy under sedation.AIM To evaluate the efficacy and safety of propofol target-controlled infusion(TCI)in combination with butorphanol for sedation during colonoscopy.METHODS In this controlled clinical trial,a total of 106 patients,who were scheduled for sedated colonoscopy,were prospectively recruited and assigned into three groups to receive different doses of butorphanol before propofol TCI:Low-dose butorphanol group(5μg/kg,group B1),high-dose butorphanol group(10μg/kg,group B2),and control group(normal saline,group C).Anesthesia was achieved by propofol TCI.The primary outcome was the median effective concentration(EC50)of propofol TCI,which was measured using the up-and-down sequential method.The secondary outcomes included AEs in perianesthesia and recovery characteristics.RESULTS The EC50 of propofol for TCI was 3.03μg/mL[95%confidence interval(CI):2.83-3.23μg/mL]in group B2,3.41μg/mL(95%CI:3.20-3.62μg/mL)in group B1,and 4.05μg/mL(95%CI:3.78-4.34μg/mL)in group C.The amount of propofol necessary for anesthesia was 132 mg[interquartile range(IQR),125-144.75 mg]in group B2 and 142 mg(IQR,135-154 mg)in group B1.Furthermore,the awakening concentration was 1.1μg/mL(IQR,0.9-1.2μg/mL)in group B2 and 1.2μg/mL(IQR,1.025-1.5μg/mL)in group B1.Notably,the propofol TCI plus butorphanol groups(groups B1 and B2)had a lower incidence of anesthesia AEs,when compared to group C.Furthermore,no significant differences were observed in the rates of AEs in perianesthesia,including hypoxemia,sinus bradycardia,hypotension,nausea and vomiting,and vertigo,among group C,group B1 and group B2.CONCLUSION The combined use with butorphanol reduces the EC50 of propofol TCI for anesthesia.The decrease in propofol might contribute to the reduced anesthesia-related AEs in patients undergoing sedated colonoscopy.

Propofol Target-Controlled Infusion Modeling in Rabbits:Pharmacokinetic and Pharmacodynamic Analysis

This study aimed to establish a new propofol target-controlled infusion（TCI） model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol（10 mg/kg） was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using Win Nonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend. The pharmacodynamics was analyzed using a sigmoidal inhibitory maximal effect model for narcotrend index（NI） versus effect-site concentration. The results showed the pharmacokinetics of propofol in Japanese white rabbits was best described by a two-compartment model. The target plasma concentrations of propofol required at light anesthetic depth was 9.77±0.23 μg/m L, while 12.52±0.69 μg/m L at deep anesthetic depth. NI was 76.17±4.25 at light anesthetic depth, while 27.41±5.77 at deep anesthetic depth. The effect-site elimination rate constant（ke0） was 0.263/min, and the propofol dose required to achieve a 50% decrease in the NI value from baseline was 11.19 μg/m L（95% CI, 10.25–13.67）. Our results established a new propofol TCI animal model and proved the model controlled the anesthetic depth accurately and stably in rabbits. The study provides a powerful method for exploring general anesthetic mechanisms at different anesthetic depths in vivo.

Effect of etomidate added to propofol target-controlled infusion in bidirectional endoscopy:A randomized clinical trial

BACKGROUND Propofol has been widely used in bidirectional gastrointestinal endoscopy sedation;however,it frequently leads to cardiovascular adverse events and respiratory depression.Propofol target-controlled infusion(TCI)can provide safe sedation but may require higher dosages of propofol.On the contrary,etomidate offers hemodynamic stability.AIM To evaluate the effect of different dose etomidate added to propofol TCI sedation during same-visit bidirectional endoscopy.METHODS A total of 330 patients from Fujian Provincial Hospital were randomly divided into three groups:P,0.1EP,and 0.15EP.Patients in the P group received propofol TCI only,with an initial effect-site concentration of the propofol TCI system of 3.0 mg/mL.Patients in the 0.1EP and 0.15EP groups received 0.1 and 0.15 mg/kg etomidate intravenous injection,respectively,followed by propofol TCI.RESULTS Patients in the 0.15EP group had higher mean blood pressure after induction than the other groups(P group:78 mmHg,0.1EP group:82 mmHg,0.15EP group:88 mmHg;P<0.05).Total doses of propofol consumption significantly decreased in the 0.15EP group compared with that in the other groups(P group:260.6 mg,0.1EP group:228.1 mg,0.15EP group:201.2 mg;P<0.05).The induction time was longer in the P group than in the other groups(P group:1.9±0.7 minutes,0.1EP group:1.2±0.4 minutes,0.15EP group:1.1±0.3 minutes;P<0.01).The recovery time was shorter in the 0.15EP group than in the other groups(P group:4.8±2.1 minutes,0.1EP group:4.5±1.6 minutes,0.15EP group:3.9±1.4 minutes;P<0.01).The incidence of hypotension(P group:36.4%,0.1EP group:29.1%,0.15EP group:11.8%;P<0.01)and injection pain was lower in the 0.15EP group than in the other groups(P<0.05).Furthermore,the incidence of respiratory depression was lower in the 0.15EP group than in the P group(P<0.05).Additionally,the satisfaction of the patient,endoscopist,and anesthesiologist was higher in the 0.15EP group than in the other groups(P<0.05).CONCLUSION Our findings suggest that 0.15 mg/kg etomidate plus propofol TCI can significantly reduce propofol consumption,which is followed by fewer cardiovascular adverse events and respiratory depression,along with higher patient,endoscopist,and anesthesiologist satisfaction.

Pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese surgical patients

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. Pharmacokinetics adjusted to the individual patient should improve the accuracy of TCI systems.

Relationship between depth of anesthesia and effect-site concentration of propofol during induction with the target-controlled infusion technique in elderly patients

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 （r=-0.580, P 〈0.01）. Systolic blood pressure （SBP） before intubation was significantly lower in Group S1 than in Groups S2 and S3. SBP and HR after intubation in the three groups were significantly increased when compared with pre-intubation values, but they did not exceed baseline values Conclusions During the TCI induction, Ce of propofol with （1.9±0.3） pg/ml may make the elderly patients unconscious. When remifentanil with a Ce of 4.0 ng/ml is added a Ce of propofol with （2.8±0.3） pg/ml is suitable for intubation. The Ce of propofol has a close correlation with the BIS values. Also, a two-step TCI technique seems to be a more suitable method of anesthesia induction in elderly patients compared with the no-stepwise TCI technique and three-step TCI technique.

Two-stage analysis of pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese patients

Background Sufentanil is a suitable choice for target-controlled infusion （TCI） because of its shorter context-sensitive half-time. The current study was to estimate the pharmacokinetics of sufentanil TCI in Chinese patients using the two-stage analysis. Methods Twelve adult patients with American Society of Anesthesiologists （ASA） physical status I or II undergoing elective surgery under general anesthesia were included. Anesthesia was induced with propofol, rocuronium and sufentanil administered by TCI lasting for 30 minutes, with target effect-site concentration of sufentanil 4 or 6 ng/ml. Frequent arterial blood samples （1.5 ml） were taken during and up to 24 hours after sufentanil TCI. Before the end of surgery, another arterial blood sample （1.0 ml） was drawn for the blood-gas analysis. Plasma sufentanil concentrations were determined by liquid chromatography-tandem mass spectrometry （limit of quantitation was 5 pg/ml）. The data were analyzed with the two-stage approach, linear regression and correlation analysis. Results The pharmacokinetics of sufentanil TCI were adequately described by a three-compartment model. The variables were derived as follows： the volume of central compartment （V1） was 5.4 L, volume of distribution at steady-state （Vdss） was 222.6 L, metabolic clearance （CI1） was 0.84 L/min and elimination half-life （t~/2y） was 389 minutes. Patients＇ age, gender and PaCO2 correlated significantly with the pharmacokinetic parameters. The Vdss, volume of slowly equilibrating compartment （V3） and t1/2 y increased, and rapid distribution clearance （012） decreased with increasing patient age. Male patients had larger values of Vdss, volume of rapidly equilibrating compartment （V2） and V3 than female patients. The Vdss and V3 increased with higher PaCO2 values. There were no significant correlations between the pharmacokinetic variables and body weight, height, lean body mass, plasma albumin, sufentanil dose, duration of surgery, pH or base excess of blood （BE-B）. Conclusions The pharmacokinetics of sufentanil TCI in Chinese patients can be optimally described by a three-compartment model. The pharmacokinetic analysis technique may affect the pharmacokinetic parameters and correlations.

Comparison of C50 for Propofol-remifentanil Target-controlled Infusion and Bispectral Index at Loss of Consciousness and Response to Painful Stimulus in Elderly and Young Patients

Background：In this prospective randomized study,we compared the predicted blood and effect-site C50 for propofol and remifentanil target-controlled infusion （TCI） and the bispectral index （BIS） values at loss of consciousness （LOC） and response to a standard noxious painful stimulus （LOS） in elderly and young patients,respectively.We hypothesized that the elderly patients will require lower target concentration of both propofol and remifentanil at above two clinical end-points.Methods：There were 80 American Society of Anesthesiologists （ASA） physical status Ⅰ Ⅱ unpremedicated patients enrolled in this study,they were divided into elderly group （age ≥65 years,n =40） and young group （aged 18-54 years,n =40）.Propofol was initially given to a predicted blood concentration of 1.2 μg/ml and thereafter increased by 0.3 μg/ml every 30 s until Observer＇s Assessment of Alertness and Sedation score was 1.The propofol level was kept constant,and remifentanil was given to provide a predict blood concentration of 2.0 ng/ml,and then increased by 0.3 ng/ml every 30 s until loss of response to a tetanic stimulus.BIS （version 3.22,BIS Quattro sensor） was also recorded.Results：In elderly group,the propofol effect-site C50 at LOC of was 1.5 （1.4-1.6） μg/ml,was significantly lower than that of young group,which was 2.2 （2.1-2.3） μg/ml,the remifentanil effect-site C50 at LOS was 3.5 （3.3-3.7） ng/ml in elderly patients,was similar with 3.7 （3.6-3.8） ng/ml in young patients.Fifty percent of patients lost consciousness at a BIS value of 57.3 （56.4-58.1）,was similar with that of young group,which was 55.2 （54.0-56.3）.Conclusion：In elderly patients,the predicted blood and effect-site concentrations of propofol at LOC were lower than that of young patients.At same sedation status,predicted blood and effect-site concentrations of remifentanil required at LOS were similar in elderly and young patients.BIS were not affected by age.Low-propofol/high-opioid may be optional TCI strategy for elderly patients.

Concentrations of propofol in cerebral spinal fluid: target-controlled infusion

Background Although the performance of target-controlled infusion (TCI) have been studied extensively, the accuracy and safety of a TCI system that targets the effect site remains to be demonstrated. This study was to investigate the relations of TCI of propofol to its concentrations in cerebral spinal fluid (CSF), the effect-site concentrations and bispectral index (BIS).Methods Twelve mongrel dogs were used for investigations. The target effect-site concentration was set at 3μg/ml and the infusion was lasted for 15 minutes. CSF and blood samples were then collected and propofol concentrations were determined by using high performance liquid chromatography with fluorescence detection. BIS and hemodynamic data were monitored continuously.Results The predicted plasma concentrations were generally overestimated. Median performance error (MDPE) and absolute median performance error (MDAPE) were -10.0% and 29.9% respectively. Propofol CSF concentrations were much lower than its effect-site concentrations. Changes in BIS were consistent with propofol concentrations in CSF, both of which changed direction at 5 minutes while the effect-site concentrations relatively lagged behind. Better correlation ( r2 = 0. 9195) was found between BIS and CSF concentrations, when compared with that between BIS and effect-site concentrations (r2=0. 554).Conclusion With 1% enflurane inhaled, the inconsistency of drug effect to the effect-site concentrations may result from inaccuracy of pharmacokinetic parameters. CSF may show effect-site concentrations more accurately than plasma when using target effect-site concentration infusion.

Advancing treatment strategies:Insights from network meta-analysis of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.

Hepatic artery infusion chemotherapy:A resurgence

In this manuscript,we comment on the article by Zhou et al,who assessed the efficacy of hepatic arterial infusion chemotherapy(HAIC)and its combination strategies for advanced hepatocellular carcinoma(HCC)using network metaanalysis methodology.We focus specifically on the potential advantages and role of HAIC in the treatment algorithm for advanced HCC.However,there remains numerous knowledge gaps before the role of HAIC can be established.There is significant heterogeneity of HAIC regimes with difficult interpretation of the clinical outcomes.Additionally,there is a lack of direct comparative data between HAIC,systemic chemotherapy,novel immunotherapies and targeted therapies.The underlying biochemical mechanisms that might explain the efficacy of HAIC and its effect on the HCC microenvironment requires further research.In the developing era of nanotechnology and targeted drug delivery systems,there is potential for integration of HAIC with novel technologies to effectively treat advanced HCC whilst minimising systemic complications.

Hepatic arterial infusion pump chemotherapy for colorectal liver metastases: Revisiting traditional techniques to explore new frontiers

Hepatic arterial infusion(HAI)chemotherapy,first introduced in the 1980s,has gained recognition as an effective locoregional treatment for colorectal liver metastasis(CRLM).Initially used for unresectable liver metastases,HAI’s app-lication has expanded to the adjuvant setting following hepatic resection,with early studies indicating improved hepatic disease-free survival.Recent research demonstrates that combining HAI with modern systemic therapies enhances conversion to resectability and prolongs both recurrence-free and overall survival,even in heavily pretreated patients with diverse RAS mutational statuses.Person-alization through approaches like microsatellite instability status and dose mo-difications further optimize outcomes.However,the complexity of HAI requires expertise across multidisciplinary teams,limiting its widespread adoption to specialized centers.Ongoing clinical trials continue to investigate HAI’s role in CRLM management,highlighting its potential to become a cornerstone of liver-directed therapy.We explore how HAI chemotherapy,in combination with personalized medicine,can advance treatment strategies for metastatic colorectal cancer.

Anticipation for hepatic arterial infusion chemotherapy in the treatment of hepatocellular carcinoma

Hepatic arterial infusion chemotherapy (HAIC) is an advanced targeted therapeuticapproach for hepatocellular carcinoma (HCC), the most common type ofprimary liver cancer. HAIC has demonstrated significant potential in managingadvanced HCC, particularly in regions with high prevalence rates. Despite itspromise, several challenges and areas for future research remain. Clinical studieshave substantiated the efficacy of HAIC in enhancing survival outcomes forpatients with advanced hepatic carcinoma. Notably, combination therapiesinvolving immune checkpoint inhibitors, such as lenvatinib and programmeddeath-1 inhibitors, have shown substantial improvements in median overallsurvival and progression-free survival compared to systemic chemotherapy.These combination therapies have also exhibited superior response rates anddisease control, with manageable and often less severe adverse events relative tosystemic treatments. This article is based on the review by Zhou et al and aims todiscuss the current status and future directions in the treatment of HCC, emphasizingthe role of HAIC and its integration with novel therapeutic agents.

Innovative applications and research progress of hepatic arterial infusion chemotherapy in the treatment of advanced hepatocellular carcinoma

This article provides an in-depth analysis of the study conducted by Wang et al,which explores hepatic arterial infusion chemotherapy and its synergistic strategies in managing advanced hepatocellular carcinoma(HCC).HCC ranks as the fourth most common cause of cancer-related mortality globally and is frequently associated with portal vein tumor thrombus(PVTT).The approach to managing HCC,particularly when PVTT is present,diverges markedly between Eastern and Western practices.These differences are rooted in variations in epidemiology,etiology,pathology,comorbidities,and prognosis.The paper delves into the diagnosis,classification,and treatment strategies for HCC with PVTT,as well as the evolving role and advancements of hepatic arterial infusion chemotherapy in the therapeutic landscape of HCC.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma:A network meta-analysis

BACKGROUND With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concentrations.However,there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study.The outcomes of interest comprised overall survival(OS),progression-free survival(PFS),tumor response and adverse events.Hazard ratios(HR)and odds ratios(OR)with a 95% confidence interval(CI)were calculated and agents were ranked based on their ranking probability.RESULTS HAIC outperformed Sorafenib(HR=0.55,95%CI:0.42-0.72;HR=0.51,95%CI:0.33-0.78;OR=2.86,95%CI:1.37-5.98;OR=5.45,95%CI:3.57-8.30;OR=7.15,95%CI:4.06-12.58;OR=2.89,95%CI:1.99-4.19;OR=0.48,95%CI:0.25-0.92,respectively)and transarterial chemoembolization(TACE)(HR=0.50,95%CI:0.33-0.75;HR=0.62,95%CI:0.39-0.98;OR=3.08,95%CI:1.36-6.98;OR=2.07,95%CI:1.54-2.80;OR=3.16,95%CI:1.71-5.85;OR=2.67,95%CI:1.59-4.50;OR=0.16,95%CI:0.05-0.54,respectively)in terms of efficacy and safety.HAIC+lenvatinib+ablation,HAIC+ablation,HAIC+anti-programmed cell death 1(PD-1),and HAIC+radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone.HAIC+TACE+S-1,HAIC+lenvatinib,HAIC+PD-1,HAIC+TACE,and HAIC+sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC.HAIC+PD-1,HAIC+TACE+S-1 and HAIC+TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.CONCLUSION HAIC proved more effective and safer than sorafenib and TACE.Furthermore,combined with other interventions,HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Camrelizumab,apatinib and hepatic artery infusion chemotherapy combined with microwave ablation for advanced hepatocellular carcinoma

BACKGROUND Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib(TRIPLET protocol)is promising for advanced hepatocellular carcinoma(Ad-HCC).However,the usefulness of microwave ablation(MWA)after TRIPLET is still controversial.AIM To compare the efficacy and safety of TRIPLET alone(T-A)vs TRIPLET-MWA(TM)for Ad-HCC.METHODS From January 2018 to March 2022,217 Ad-HCC patients were retrospectively enrolled.Among them,122 were included in the T-A group,and 95 were included in the T-M group.A propensity score matching(PSM)was applied to balance bias.Overall survival(OS)was compared using the Kaplan-Meier curve with the log-rank test.The overall objective response rate(ORR)and major complications were also assessed.RESULTS After PSM,82 patients were included both the T-A group and the T-M group.The ORR(85.4%)in the T-M group was significantly higher than that(65.9%)in the T-A group(P<0.001).The cumulative 1-,2-,and 3-year OS rates were 98.7%,93.4%,and 82.0%in the T-M group and 85.1%,63.1%,and 55.0%in the T-A group(hazard ratio=0.22;95%confidence interval:0.10-0.49;P<0.001).The incidence of major complications was 4.9%(6/122)in the T-A group and 5.3%(5/95)in the T-M group,which were not significantly different(P=1.000).CONCLUSION T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.

Anthocyanins from purple corn affect gut microbiota and metabolome in inflammatory bowel disease patients under infliximab infusion: the SiCURA pilot study

Nowadays,inflammatory bowel disease(IBD)-patient therapies are mainly based on corticosteroid,thiopurine,and immunomodulator treatments.Patients with active disease,that do not respond to corticosteroid and/or thiopurine treatment,can switch to the usage of the chimeric monoclonal antibody infliximab(IFX).However,to date,no treatment appeared to be conclusive in lowering the incidence of IBD relapses.With the aim to increase the effectiveness of IFX treatment,we combined it with an adjuvant purple corn supplementation enriched in anthocyanins.IBD-patients were enrolled before they underwent to the IFX-infusion,and they were allocated in 2 different study arms.Patients in the intervention-arm followed a dietary supplementation with purple corn water-soluble extract,whereas control patients had a daily consumption of red fruit tea.16S rDNA gene-sequencing and high-resolution mass-spectrometry metabo-lipidomics analyses were conducted on stool and sera samples,respectively.As a result,the experimental intervention mainly affected the serum metabolome of IBD-patients by decreasing the concentration of specific lipids.Focusing on IBD patient annotated taxa,a significant decrease in Lactobacillus and Bifi dobacterium relative abundances was found.As far as it concerns the ulcerative colitis patient subset,the experimental intervention led to a decrease in Alistipes and Erysipelotrichaceae UCG-003 genus abundances and a concomitant Parabacteroides increase.On the contrary,after treatment,Crohn’s disease patients did not exhibit metataxonomics differences at the genus level.At the end of the treatment that led to a reshaped microbiota community,the gathered data paves the way for the usage of a specifically designed probiotic supplementation as a valuable strategy for IBD-patients under IFX infusion.

Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.

Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma

Hepatic artery infusion chemotherapy(HAIC)has good clinical efficacy in the treatment of advanced hepatocellular carcinoma(HCC);however,its efficacy varies.This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications.As of October 25,2023,51 articles have been retrieved based on keyword predictions and HAIC.Sixteen eligible articles were selected for inclusion in this study.Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing,gene testing,and imaging testing.The above indicators and their combined forms showed excellent predictive effects in retrospective studies.This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC,analyzed each marker's ability to predict HAIC efficacy,and provided a reference for the clinical application of the prediction system.