Analysis of the therapeutic effect of transhepatic arterial embolization combined with microwave ablation for hepatic epithelioid hemangioendothelioma

Objective:To analyze the imaging results of hepatic epithelioid hemangioendothelioma(HEHE)and the effect of transhepatic arterial embolization(TAE)combined with microwave ablation(MWA)in the treatment of HEHE.Methods:A retrospective analysis of four patients with HEHE diagnosed by pathological diagnosis of liver biopsy was performed.

Role of peripheral amyloid-β aggregates in Alzheimer’s disease: mechanistic, diagnostic, and therapeutic implications

Compelling evidence demonstrates that the levels of peripheral amyloid-β(Aβ)fluctuate in Alzheimer’s disease(AD)patients.Moreover,Aβdeposits have been identified in peripheral tissues.However,the relevance of peripheral Aβ(misfolded or not)in pathological situations,and the temporal appearance of these pathological fluctuations,are not well understood.The presence of misfolded Aβin peripheral compartments raises concerns on potential inter-individual transmissions considering the well-reported prion-like properties of this disease-associated protein.The latter is supported by multiple reports demonstrating that Aβmisfolding can be transmitted between humans and experimental animals through multiple routes of exposure.In this mini-review,we discuss the potential implications of peripheral,disease-associated Aβin disease mechanisms,as well as in diagnostic and therapeutic approaches.

In vivo direct neuronal conversion as a therapeutic strategy for ischemic stroke

Stroke causes neuronal loss,which ultimately results in persistent neurological dysfunction.Globally,stroke was the third-leading cause of death and disability combined in all ages in 2019,after neonatal disorders and ischemic heart disease.In that year,there were 12.2 million incident strokes,101 million prevalent strokes,and 143 million disability-adjusted life-years due to stroke.

PI3K/AKT signaling and neuroprotection in ischemic stroke:molecular mechanisms and therapeutic perspectives

It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers.This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling pathway.The key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke.Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.

Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

Transanal eco-Doppler evaluation after hemorrhoidal artery embolization

BACKGROUND Hemorrhoidal artery embolization(Emborrhoid)is a novel method for the treatment of severe hemorrhoidal bleeding.Despite having a technical success rate of 93%-100%,the clinical success ranges between 63%and 94%,with a rebleeding rate of 13.6%.AIM To evaluate the effectiveness of this procedure in reducing hemorrhoidal flow and hemorrhoidal bleeding.METHODS This prospective observational pilot study was conducted at Division of General Surgery 1 and Tertiary Referral Pelvic Floor Center,Treviso Regional Hospital,Italy.In a 2 months period(February-March 2022),consecutive patients with hemorrhoidal bleeding scores(HBSs)≥4,Goligher scores of II or III,failure of non-operative management,and a candidate for Emborrhoid were included.Endoanal ultrasound with eco-Doppler was performed preoperatively and 1 month after the procedure.The primary endpoint was to quantify the changes in arterial hemorrhoidal flow after treatment.The secondary endpoint was to evaluate the correlation between the flow changes and the HBS.RESULTS Eleven patients underwent Emborrhoid.The overall pretreatment mean systolic peak(MSP)was 14.66 cm/s.The highest MSP values were found in the anterior left lateral(17.82 cm/s at 1 o’clock and 15.88 cm/s at 3 o’clock)and in the posterior right lateral(14.62 cm/s at 7 o’clock and 16.71 cm/s at 9 o’clock)quadrants of the anal canal.After treatment,the overall MSP values were significantly reduced(P=0.008)although the correlation between MSP and HBS changes was weak(P=0.570).A statistical difference was found between distal embolization compared with proximal embolization(P=0.047).However,the coil landing zone was not related to symptoms improvement(P=1.000).A significant difference in MSP changes was also reported between patients with type 1 and type 2 superior rectal artery(SRA)anatomy(P=0.040).No relationship between hemorrhoidal grades(P=1.000),SRA anatomy(P=1.000)and treatment outcomes was found.CONCLUSION The preliminary findings of this pilot study confirm that Emborrhoid was effective in reducing the arterial hemorrhoidal flow in hemorrhoidal disease.However,the correlation between the post-operative MSP and HBS changes was weak.Hemorrhoidal grade,SRA anatomy and type of embolization were not related to treatment outcomes.

Modulatory role of plant-derived metabolites on host-microbiota interactions:personalized therapeutics outlook

A diverse array of microbes in and on the human body constitute the microbiota.These micro-residents continuously interact with the human host through the language of metabolites to dictate the host’s physiology in health and illnesses.Any biotic and abiotic component ensuring a balanced host-microbiota interaction are potential microbiome therapeutic agents to overcome human diseases.Plant metabolites are continually being used to treat various illnesses.These metabolites target the host’s metabolic machinery and host-gut microbiota interactions to overcome human diseases.Despite the paramount therapeutic significance of the factors affecting host-microbiota interactions,a comprehensive overview of the modulatory role of plant-derived metabolites in host-microbiota interactions is lacking.The current review puts an effort into comprehending the role of medicinal plants in gut microbiota modulation to mitigate various human illnesses.It would develop a holistic understanding of hostmicrobiota interactions and the role of effectors in health and diseases.

Transarterial embolization is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive malignant neoplasm that requires liver transplantation(LT).Despite patients with HCC being prioritized by most organ allocation systems worldwide,they still have to wait for long periods.Locoregional therapies(LRTs)are employed as bridging therapies in patients with HCC awaiting LT.Although largely used in the past,transarterial embolization(TAE)has been replaced by transarterial chemoembolization(TACE).However,the superiority of TACE over TAE has not been consistently shown in the literature.AIM To compare the outcomes of TACE and TAE in patients with HCC awaiting LT.METHODS All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included.All patients underwent LRT with either TACE or TAE.Some patients also underwent percutaneous ethanol injection(PEI),concom-itantly or in different treatment sessions.The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus.The primary outcome was waitlist dropout due to tumor progression,and the secondary outcome was the occurrence of adverse events.In the subset of patients who underwent LT,complete pathological response and post-transplant recurrence-free survival were also assessed.RESULTS Twelve(18.5%)patients in the TACE group(only TACE and TACE+PEI;n=65)and 3(7.9%)patients in the TAE group(only TAE and TAE+PEI;n=38)dropped out of the waitlist due to tumor progression(P log-rank test=0.29).Adverse events occurred in 8(12.3%)and 2(5.3%)patients in the TACE and TAE groups,respectively(P=0.316).Forty-eight(73.8%)of the 65 patients in the TACE group and 29(76.3%)of the 38 patients in the TAE group underwent LT(P=0.818).Among these patients,complete pathological response was detected in 7(14.6%)and 9(31%)patients in the TACE and TAE groups,respectively(P=0.145).Post-LT,HCC recurred in 9(18.8%)and 4(13.8%)patients in the TACE and TAE groups,respectively(P=0.756).Posttransplant recurrence-free survival was similar between the groups(P log-rank test=0.71).CONCLUSION Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC.Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.

Therapeutic Effect of Transcatheter Arterial Chemoembolization Combined with Percutaneous Ethanol Injection in Hepatocellular Carcinoma

Objective To evaluate the clinical efficacy of the combined treatment with transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) on hepatocellular carcinoma (HCC) .Methods 312 patients with moderate or advanced HCCs were divided into two groups; 170 cases underwent TACE treatment alone, 142 cases were treated with TACE and PEI under B-ultrasound guidance.Results The rates of reduction in tumor diameter and the decline in serum AFP level were 41.2% and 40.4% in the TACE group and 75.4% and 74.1 % in the TACE + PEI group respectively. The 6, 12 and 24 months survival rates in the TACE group were 77.1 % , 34.1% and 18.8% ,respectively and in the TACE + PEI group 87.3% , 62.0% and 38.0% , respectively. Overall, there was a significant difference between the two treatment groups ( P < 0.05). Conclusion Treatment on HCCs with TACE + PEI is convenient, safe and results in better survival rates than TACE alone.

Advances in Zika virus vaccines and therapeutics:A systematic review

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

Portal vein embolization failure:Current strategies and future perspectives to improve liver hypertrophy before major oncological liver resection

Portal vein embolization(PVE)is currently considered the standard of care to improve the volume of an inadequate future remnant liver(FRL)and decrease the risk of post-hepatectomy liver failure(PHLF).PHLF remains a significant limitation in performing major liver surgery and is the main cause of mortality after resection.The degree of hypertrophy obtained after PVE is variable and depends on multiple factors.Up to 20%of patients fail to undergo the planned surgery because of either an inadequate FRL growth or tumor progression after the PVE procedure(usually 6-8 wk are needed before surgery).The management of PVE failure is still debated,with a lack of consensus regarding the best clinical strategy.Different additional techniques have been proposed,such as sequential transarterial chemoembolization followed by PVE,segment 4 PVE,intra-portal administration of stem cells,dietary supplementation,and hepatic vein embolization.The aim of this review is to summarize the up-to-date strategies to overcome such difficult situations and discuss future perspectives on improving FRL hypertrophy.

Comparative study between Embosphere®and Marine gel®as embolic agents for chemoembolization of hepatocellular carcinoma

BACKGROUND While gelatin sponge particles and calibrated microspheres are commonly used as embolic materials in conventional transarterial chemoembolization(cTACE),direct comparisons between these embolic agents are rare.AIM To compare the efficacy and safety of superselective cTACE using Embosphere®or Marine gel®in patients with early-stage hepatocellular carcinoma(HCC).METHODS This retrospective study included 70 patients with small(<4 cm)HCC who underwent cTACE with Embosphere®(n=33)or Marine gel®(n=37)as the embolic agent at a single center between March 2021 and July 2022.The radiologic images and clinical data were retrospectively reviewed,with an emphasis on tumor response,procedure-related complications,and local tumor recurrence.The primary index tumor was assessed on a 1-mo follow-up image,and local progression-free survival was obtained using the Kaplan-Meier method and was compared by the log-rank test.RESULTS The median tumor size of both groups was 1.5 cm,and 69 patients achieved a complete response one month after cTACE.The cumulative local recurrence rate at 12 mo was 15.5%in the Embosphere®group and 14.4%in the Marine gel®group.The local progression-free survival was not significantly different between the two groups(P=0.83).In the multivariate analysis,high serum alphafetoprotein was the only significant poor prognostic factor for local tumor progression(P=0.01).Postembolization syndrome occurred in 36.4%of the Embosphere®group and 35.1%of the Marine gel®group,and there were no cases of biloma,biliary duct dilation,or liver abscess in either group.CONCLUSION Calibrated gelatin sponge particles(Marine gel®)and calibrated microspheres(Embosphere®)have similar outcomes in terms of tumor response for superselective cTACE of small HCC.

Impact of uterine artery embolization on ovarian function and pregnancy outcome after uterine-fibroids treatment:A prospective study

Uterine fibroids are benign tumors that originate from smooth muscle cells of the uterus.It is the most common gynecological disorder,affecting up to 80%of women of reproductive age.Uterine fibroids can cause various symptoms such as abnormal uterine bleeding,pelvic pain,infertility,and pregnancy complications.The treatment options for uterine fibroids include medical therapy,surgical intervention,and minimally invasive techniques.AIM To compare ovarian function of women with uterine fibroids who did or did not undergo uterine artery embolization(UAE).METHODS This prospective cohort study enrolled 87 women with symptomatic uterine fibroids who underwent UAE,and 87 women with the same symptoms who did not undergo UAE but received conservative management or other treatments.The two groups were matched for age,body mass index,parity,and baseline characteristics of uterine fibroids.The primary outcome was ovarian function that was evaluated by serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),and anti-Müllerian hormone(AMH),as well as ovarian reserve tests,such as antral follicle count(AFC)and ovarian volume(OV).The secondary outcome was fertility that was evaluated based on the menstrual cycle,ovulation,conception,pregnancy,and delivery.The participants were followed-up for 36 months and assessed at 1,3,6,12,24,and 36 months after treatment.RESULTS The study found that the most common minor complication of UAE was postembolization syndrome in 73.6% of women,resolving within a week.No significant differences were observed between the UAE group and the control group in serum levels of reproductive hormones(FSH,LH,E2,AMH)and ovarian reserve indicators(AFC,OV)at any point up to 36 months post-treatment.Additionally,there were no significant differences in conception,pregnancy,or delivery rates,with the average time to conception and gestational age at delivery being similar between the two groups.Birth weights were also comparable.Finally,there was no significant correlation between ovarian function,fertility indicators,and the type or amount of embolic agent used or the change in fibroids posttreatment.CONCLUSION UAE resulted in significantly positive pregnancy outcomes,no adverse events post-treatment,and is a safe and effective treatment for uterine fibroids that preserves ovarian function and fertility.

Pyomyoma as a Complication of Uterine Artery Embolization (A Case Report)

Pyomoyoma is a rare complication of Uterine Artery Embolization (UAE). This case report reflects on this condition. A 45-year-old female, a known case of adenomyosis, presented with intermittent fever and foul vaginal discharge. These symptoms occurred shortly after the patient underwent UAE for menorrhagia secondary to adenomyosis. Computed tomography scan of the abdomen and pelvis aided in the diagnosis of Pyomyoma secondary to UAE. After a trial of broad spectrum antibiotics and Suction and Evacuation of the uterus had little to no help in the patient’s condition, she underwent Total Abdominal Hysterectomy in which a big, organized pus collection was removed from the uterus. Conclusion: Pyomyoma should be considered in the differentials for patients presenting with fever and vaginal discharge post UAE.

Spontaneous Paravesical and Broad Ligament Hematoma after Vaginal Delivery Had Uterine Artery Embolization after Evacuating the Hematoma

Broad ligament hematoma is typically seen during cesarean section due to rupture of branches of uterine and vaginal vessels and it’s rare to be seen post-normal vaginal delivery. Addressing puerperal hematomas postpartum presents considerable challenges for obstetric care providers. While hematomas such as those affecting the vulva, vulvovaginal region, or paravaginal area are frequently encountered, retroperitoneal hematomas are rare and notably pose a greater risk to the life of the patient. The medical literature contains scant case reports on retroperitoneal hematomas, with no consensus on a definitive treatment approach. Pelvic arterial embolization has emerged as both a sensible and increasingly preferred method for treating these hematomas recently, but its application is contingent upon the patient maintaining hemodynamic stability and the availability of a specialized interventional embolization unit. In our case, we are presenting a very rare case of a 31-year-old primigravida female with a history of in vitro fertilization pregnancy. She delivered a normal vaginal delivery at 31 weeks gestation. Unfortunately, she experienced multiple complications intrapartum, including preeclampsia and placental abruption. These complications increased her risk of developing a broad ligament hematoma.

Influence of transcatheter arterial embolization on symptom distress and fatigue in liver cancer patients

BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignancy,and transcatheter arterial embolization(TAE)has emerged as a pivotal therapeutic modality.How-ever,TAE may induce symptom distress and fatigue,adversely affecting the quality of life of patients.AIM To investigate symptom distress,fatigue,and associated factors in HCC patients undergoing TAE.METHODS We used a cross-sectional design and purposive sampling to enroll HCC patients who underwent TAE at our institution from January to December 2022.Question-naires were utilized to collect data on symptom distress and fatigue scores from the first to the third day after TAE.RESULTS Our study revealed a significant reduction in fatigue and symptom distress among patients after TAE.Pain,fatigue,insomnia,fever and abdominal dis-tension were the most common symptoms troubling patients during the first 3 d post-TAE.Marital status,presence of family support,physical functional status,age,and symptom distress were identified as predictors of fatigue in patients.CONCLUSION Healthcare professionals should educate HCC patients on symptom distress and INTRODUCTION Hepatocellular carcinoma(HCC)ranks as the fifth most prevalent cancer and the third leading cause of cancer-related mortality globally.Surgical intervention remains the cornerstone of HCC treatment;however,due to the challenges associated with early diagnosis and the lack of specific diagnostic markers,a considerable proportion of patients are diagnosed at advanced stages,rendering them ineligible for surgical interventions.Transcatheter arterial embolization(TAE)is an interventional therapeutic approach involving the insertion of a fine catheter via the femoral artery to reach the vasculature near the tumor site.TAE aims to obstruct the arterial supply to the tumor by deploying embolic agents,thereby inducing necrosis in cancer cells.This procedure is suitable for patients with good liver function and overall health,particularly those with large HCCs that have not invaded the portal vein[1,2].Nonetheless,following TAE,hepatocytes incur variable degrees of damage,leading to the development of a constel-lation of symptoms reminiscent of acute hepatitis.These symptoms include fatigue and systemic discomfort,such as nausea,vomiting,fever,abdominal pain,as well as transient elevations in aspartate aminotransferase(AST)and alanine aminotransferase(ALT),collectively referred to as postembolization syndrome[3,4].These symptoms may arise due to ischemia of the liver and gallbladder,temporary liver enlargement,and peritoneal irritation.While many studies have explored fatigue and symptom distress in cancer patients both nationally and internationally,with some focusing on symptom distress following transcatheter arterial chemoembolization,there has been limited in-depth investigation into the fatigue and symptom distress resulting from TAE treatment[5-8].Fatigue and pain are both subjective experiences,typically arising from the gradual depletion of energy reserves during the course of illness[9].Fatigue is particularly prevalent among cancer patients,with rates soaring as high as 90%.Despite extensive research exploring cancer-related fatigue and its influencing factors,a unanimous consensus remains elusive.Hence,the primary objective of this study was to investigate the symptom distress and fatigue experienced by liver cancer patients following TAE treatment and to analyze potential contributing factors.

Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics

In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and compliance.Pharmaceutical specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered appropriately.Conformance of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance criteria.Quality attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the specifications.Acceptance criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric specifications.Discussed in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial monographs.Outlooks are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.

Combined transarterial chemoembolization and tislelizumab for patients with unresectable hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)often presents as unresectable,necessitating effective treatment modalities.Combining transarterial chemoembolization(TACE)with immunotherapy and targeted therapy has shown promise,yet real-world evidence is needed.AIM To investigate effectiveness and safety of TACE with tislelizumab±targeted therapy for unresectable HCC in real-world setting.METHODS This retrospective study included patients with unresectable HCC receiving combined treatment of TACE and tislelizumab.The clinical outcomes included progression-free survival(PFS),overall survival(OS),objective response rate(ORR),and disease control rate(DCR).All patients were evaluated according to the mRECIST criteria.The adverse event(AE)was also assessed.RESULTS In this study of 56 patients with median follow-up of 10.9 months,7 had previous immunotherapy.Tislelizumab was administered before TACE in 21(37.50%)and after in 35(62.50%)patients,with 91.07%receiving concurrent targeted therapy.Median PFS was 14.0(95%CI:7.0-18.00)months,and OS was 28(95%CI:2.94-53.05)months.Patients with prior immunotherapy had shorter PFS(6 vs.18 months,P=0.006).Overall ORR and DCR were 82.14%and 87.50%.Grade≥3 treatment-related AEs included increased alanine aminotransferase(8.93%),aspartate aminotransferase(10.71%),and total bilirubin(3.57%).CONCLUSION The combination of TACE and tislelizumab,with or without targeted therapy,demonstrated promising efficacy and safety in unresectable HCC,especially in immunotherapy-naive patients,warranting further prospective validation studies.