Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

Identification of the key genes and mechanisms associated with transcatheter arterial chemoembolisation refractoriness in hepatocellular carcinoma

BACKGROUND Transcatheter arterial embolisation(TACE)is the primary treatment for intermediate-stage hepatocellular carcinoma(HCC)patients while some HCC cases have shown resistance to TACE.AIM To investigate the key genes and potential mechanisms correlated with TACE refractoriness in HCC.METHODS The microarray datasets of TACE-treated HCC tissues,HCC and non-HCC tissues were collected by searching multiple public databases.The respective differentially expressed genes(DEGs)were attained via limma R package.Weighted gene co-expression network analysis was employed for identifying the significant modules related to TACE non-response.TACE refractoriness-related genes were obtained by intersecting up-regulated TACE-associated and HCC-associated DEGs together with the genes in significant modules related to TACE nonresponse.The key genes expression in the above two pairs of samples was compared respectively via Wilcoxon tests and standard mean differences model.The prognostic value of the key genes was evaluated by Kaplan-Meier curve.Multivariate analysis was utilised to investigate the independent prognostic factor in key genes.Single-cell RNA(scRNA)sequencing analysis was conducted to explore the cell types in HCC.TACE refractoriness-related genes activity was calculated via AUCell packages.The CellChat R package was used for the investigation of the cell–cell communication between the identified cell types.RESULTS HCC tissues of TACE non-responders(n=66)and TACE responders(n=81),HCC(n=3941)and non-HCC(n=3443)tissues were obtained.The five key genes,DLG associated protein 5(DLGAP5),Kinesin family member 20A(KIF20A),Assembly factor for spindle microtubules(ASPM),Kinesin family member 11(KIF11)and TPX2 microtubule nucleation factor(TPX2)in TACE refractoriness-related genes,were identified.The five key genes were all up-regulated in the TACE non-responders group and the HCC group.High expression of the five key genes predicted poor prognosis in HCC.Among the key genes,TPX2 was an independent prognostic factor.Four cell types,hepatocytes,embryonic stem cells,T cells and B cells,were identified in the HCC tissues.The TACE refractoriness-related genes expressed primarily in hepatocytes and embryonic stem cells.Hepatocytes,as the providers of ligands,had the strongest interaction with embryonic stem cells that provided receptors.CONCLUSION Five key genes(DLGAP5,KIF20A,ASPM,KIF11 and TPX2)were identified as promoting refractory TACE.Hepatocytes and embryonic stem cells were likely to boost TACE refractoriness.

First platelet transfusion refractoriness in a patient with acute myelocytic leukemia: A case report

BACKGROUND Platelet transfusion is of great significance in the treatment of thrombocytopenia caused by myelosuppression during intensive chemotherapy in patients with acute leukemia.In recent years,with platelet transfusion increasing,ineffective platelet transfusion has become increasingly prominent.Generally speaking,platelet antibodies can be produced after repeated transfusion,thus rendering subsequent platelet transfusion ineffective.We report a case of first platelet transfusion refractoriness(PTR)in a patient with acute myelocytic leukemia(AML).Due to the rarity of such cases in clinical practice,there have been no relevant case reports so far.CASE SUMMARY A 51-year-old female patient attended the hospital due to throat pain and abnormal blood cells for 4 d.Her diagnosis was acute myelocytic leukemia[M2 type Fms related receptor tyrosine kinase 3,Isocitrate Dehydrogenase 1,Nucleophosmin 1,Neuroblastoma RAS viral oncogene homolog(+)high-risk group].She was treated with"IA"(IDA 10 mg day 1-3 and Ara-C 0.2 g day 1-5)chemotherapy.When her condition improved,the patient was discharged from the hospital,instructed to take medicine as prescribed by the doctor after discharge,and returned to the hospital for further chemotherapy on time.CONCLUSION We report a rare case of first platelet transfusion failure in a patient with AML during induction chemotherapy,which may be related to the production of platelet antibodies induced by antibiotics and excessive tumor load.This also suggests that we should consider the influence of antibiotics when the rare situation of first platelet transfusion failure occurs in patients with AML.When platelet antibodies are produced,immunoglobulins can be used to block antibodies,thereby reducing platelet destruction.For patients with PTR,both immune and non-immune factors need to be considered and combined in clinical practice along with individualized treatment to effectively solve the problem.

Risk factors for proton pump inhibitor refractoriness in Chinese patients with non-erosive reflux disease

AIM:To analyze risk factors for refractoriness to proton pump inhibitors(PPIs) in patients with non-erosive reflux disease(NERD).METHODS:A total of 256 NERD patients treated with the PPI esomeprazole were enrolled.They were classified into symptom-free and residual symptoms groups according to Quality of Life in Reflux and Dyspepsia(QolRad) scale.All subjects completed questionnaires on psychological status(self-rating anxiety scale;selfrating depression scale) and quality of life scale(Short Form 36).Multivariate analysis was used to determine the predictive factors for PPI responses.RESULTS:According to QolRad,97 patients were confirmed to have residual reflux symptoms,and the remaining 159 patients were considered symptom free.There were no significant differences between the two groups in lifestyle factors(smoking and alcohol consumption),age,Helicobacter pylori infection,and hiatal hernia.There were significant differences between the two groups in relation to sex,psychological distress including anxiety and depression,body mass index(BMI),and irritable bowel syndrome(IBS)(P < 0.05).Logistic regression analysis found that BMI < 23,comorbid IBS,anxiety,and depression were major risk factors for PPI resistance.Symptomatic patients had a lower quality of life compared with symptom-free patients.CONCLUSION:Some NERD patients are refractory to PPIs and have lower quality of life.Residual symptoms are associated with psychological distress,intestinal disorders,and low BMI.

Development of a computed tomography-based radiomics nomogram for prediction of transarterial chemoembolization refractoriness in hepatocellular carcinoma

BACKGROUND Some patients with hepatocellular carcinoma(HCC)are more likely to experience disease progression despite continuous transarterial chemoembolization(TACE),which is called TACE refractoriness.At present,it is still difficult to predict TACE refractoriness,although some models/scoring systems have been developed.At present,radiological-based radiomics models have been successfully applied to predict cancer patient prognosis.AIM To develop and validate a computed tomography(CT)-based radiomics nomogram for the pre-treatment prediction of TACE refractoriness.METHODS This retrospective study consisted of a training dataset(n=137)and an external validation dataset(n=81)of patients with clinically/pathologically confirmed HCC who underwent repeated TACE from March 2009 to March 2016.Radiomics features were retrospectively extracted from preoperative CT images of the arterial phase.The pre-treatment radiomics signature was generated using least absolute shrinkage and selection operator Cox regression analysis.A CT-based radiomics nomogram incorporating clinical risk factors and the radiomics signature was built and verified by calibration curve and decision curve analyses.The usefulness of the CT-based radiomics nomogram was assessed by Kaplan-Meier curve analysis.We used the concordance index to conduct head-to-head comparisons of the radiomics nomogram with the other four models(Assessment for Retreatment with Transarterial Chemoembolization score;α-fetoprotein,Barcelona Clinic Liver Cancer,Child-Pugh,and Response score;CT-based radiomics signature;and clinical model).All analyses were conducted according to the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis statement.RESULTS The median duration of follow-up was 61.3 mo(interquartile range,25.5-69.3 mo)for the training cohort and 67.1 mo(interquartile range,32.4-71.3 mo)for the validation cohort.The median number of TACE sessions was 4(range,3-7)in both cohorts.Eight radiomics features were chosen from 869 candidate features to build a radiomics signature.The CT-based radiomics nomogram included the radiomics score(hazard ratio=3.9,95%confidence interval:3.1-8.8,P<0.001)and four clinical factors and classified patients into high-risk(score>3.5)and low-risk(score≤3.5)groups with markedly different prognoses(overall survival:12.3 mo vs 23.6 mo,P<0.001).The accuracy of the nomogram was considerably higher than that of the other four models.The calibration curve and decision curve analyses verified the usefulness of the CT-based radiomics nomogram for clinical practice.CONCLUSION The newly constructed CT-based radiomics nomogram can be used for the pretreatment prediction of TACE refractoriness,which may provide better guidance for decision making regarding further TACE treatment.

Both transmural dispersion of repolarization and of refractoriness are poor predictors of arrhythmogenicity： a role for iCEB （QT/QRS）？

We read the original article by Nuis, et al. and the reply by Dogan, et al. with great interest. Nuis, et al. examined whether transcatheter aortic valve implantation （TAVI） in patients suffering from severe aortic stenosis led to changes in corrected QT dispersion （cQTD）, previously used to predict arrhythmic risk. Dogan, et al. proposed that a different marker, transmural dispersion of repolariza- tion （TDR）, has better accuracy in risk prediction.

Transarterial chemoembolization failure/refractoriness: A scientific concept or pseudo-proposition

Multi-session transarterial chemoembolization(TACE)is usually needed for the treatment of intermediate-stage hepatocellular carcinoma(HCC),but it may not always have a positive influence on prognosis due to high heterogeneity of HCC.To avoid ineffective repeated TACE,the concept of TACE failure/refractoriness has been proposed by several organizations and is being addressed using tyrosine kinase inhibitors.The concept of TACE failure/refractoriness is controversial due to ambiguous definitions and low evidence-based data.To date,only a few studies have examined the rationality concerning the definition of TACE failure/refractoriness,although the concept has been introduced and applied in many TACE-related clinical trials.This review focuses on some of the issues related to different versions of TACE failure/refractoriness,the rationality of related definitions,and the feasibility of continuing TACE after so-called failure/refractoriness based on published evidence.A suggestion to re-define TAEC failure/refractoriness is also put forward.

Refractoriness of interferon-beta signaling through NOD1 pathway in mouse respiratory epithelial cells using the anticancer xanthone compound

AIM:To explore the possibility that nucleotide oligomerization domain 1(NOD1) pathway involved in refractoriness of interferon-β signaling in mouse respiratory epithelial cells induced by the anticancer xanthone compound,5,6-dimethylxanthenone-4-acetic acid(DMXAA).METHODS:C10 mouse bronchial epithelial cells were grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum,2 mmol/L glutamine,100 units/mL penicillin,100 g/mL streptomycin.Pathogen-free female BALB/c mice were used to explore the mechanisms of refractoriness of interferon-signaling.Mouse thioglycollate-elicited peritoneal macrophages,bone marrow derived macrophages and bone marrow derived dendritic cells were collected and cultured.The amount of interferon(IFN)-inducible protein-10(IP10/CXCL10),macrophage chemotactic protein(MCP1/CCL2) and interleukin(IL)-6 secreted by cells activated by DMXAA was quantified using enzyme-linked immunosorbent assay kits according to the instructions of the manufacturers.Total RNA was isolated from cells or nasal epithelium with RNeasy Plus Mini Kit,and cDNA was synthesized.Gene expression was checked using Applied Biosystems StepOne Real-Time Polymerase Chain Reaction System.Transfection of small interfering RNA(siRNA) control,NOD1 duplexed RNA oligonucleotides,and high-mobility group box 1/2/3(HMGB1/2/3) siRNA was performed using siRNA transfection reagent.RESULTS:DMXAA activates IFN-β pathway with high level of IFN-β dependent antiviral genes including 2',5'-oligoadenylate synthetase 1 and myxovirus resistance 1 in mouse thioglycollate-elicited peritoneal macrophages,bone marrow derived macrophages and bone marrow derived dendritic cells.Activation of IFN-β by DMXAA involved in NOD1,but not HMGB1/2/3 signal pathway demonstrated by siRNA.NOD1 pathway plays an important role in refractoriness of IFN-β signaling induced by DMXAA in mouse C10 respiratory epithelial cells and BALB/c mice nasal epithelia.These data indicate that DMXAA is not well adapted to the intrinsic properties of IFN-β signaling.Approaches to restore sensitivity of IFN-β signaling by find other xanthone compounds may function similarly,could enhance the efficacy of protection from influenza pneumonia and potentially in other respiratory viral infections.CONCLUSION:NOD1 pathway may play an important role in refractoriness of IFN-β signaling in mouse respiratory epithelial cells induced by DMXAA.

Effect of Mild-calcined Coal Gangue Additionon Hot Strength and Refractoriness Under Loadof Ultra Low Cement Castablesin Al_2O_3-SiO_2 System

This work explored the way to improve hot modulus q/＇ rupture （HMOR） and refractoriness under load （RUL） by adding mild-calcined coal gangue （MCG） in Al2O3 -SiO2 ultra low cement （ULC） castables, making use of the in-situ effect of the MCG during heating-up. The influence of respective additions of 5%, 10% and 1.5% of the MCG powders calcined at 700℃ was investigated on HMOR at 1400 ℃ and RUL of the castables. With increased addition of the MCG, HMOR and RUL become significantly enhanced. At 10% of the MCG addition, HMOR reaches 3 MPa, as compared to 0. 3 MPa in the case of no MCG addition. RUL of the specimens dried at 110 ℃for 24 h can be increased by some 270 ℃ with 10% of the MCG addition. RUL 0.11 the specimens preheated at 1 500℃ for 3 h maintains the growth trend with the MCG addition increasing. The microstructure of the heated castable samples was investigated by means of SEM. The in-situ formed needle-like and interlaced mullite in the matrix is contributive to the tmprovement.

Preparation of Reference Samples for Refractoriness Under Load(Non-differential,with Rising Temperature) of Refractories

The preparation of reference samples for refractoriness under load （ non-differential, with rising temperature） of refractories was discussed. According to features and application of reference samples, quartz glass was chosen as a stand-by reference material for uniformity and stability tests. Then, the true value was fixed by gathering the testing results from many labs with stable testing levels and reliable testing results in China. The testing results from these labs were used for normality test by Shapiro-wilk method; and for abnormality value test by Grubbs method, for equal observation test by Cochran method. After confirming no abnormality values among the testing results from the labs. the average values of reference samples were calculated and the uncertainty was appraised. The results show that the standard value of reference samples is 1 386 ℃ and the expanded uncertainty is 12 ℃.

Test Method for Refractoriness Under Load of Refractory Products(Non-differential,with Rising Temperature)

This standard specifies the definitions, theory, apparatus, specimens, procedures, test results and disposal, test error and report of test method for refractoriness under load of refractory products （non-differential, with rising temperature）.

Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab:A case report

BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating UC.However,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab.CASE SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to dizziness.The patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four years.Based on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory UC.In particular,the patient showed primary nonresponse to infliximab and vedolizumab.Based on the patient’s history and recurrent disease,we decided to administer upadacitinib.During hospitalisation,the patient was received upadacitinib under our guidance.Eight weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved significantly.No notable adverse reactions have been reported to date.CONCLUSION Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

Re-evaluating Transarterial Chemoembolization Failure/Refractoriness:A Survey by Chinese College of Interventionalists

Background and Aims:The recognition of transarterial chemoembolization(TACE)failure/refractoriness among Chinese clinicians remains unclear.Using an online survey conducted by the Chinese College of Interventionalists(CCI),the aim of this study was to explore the recognition of TACE failure/refractoriness and review TACE application for hepatocellular carcinoma(HCC)treatment in clinical practice.Methods:From 27 August 2020 to 30 August 2020 during the CCI 2020 annual meeting,a survey with 34 questions was sent by email to 264 CCI clinicians in China with more than 10 years of experience using TACE for HCC treatment.Results:A total of 257 clinicians participated and responded to the survey.Most participants agreed that the concept of“TACE failure/refractoriness”has scientific and clinical significance(n=191,74.3%).Nearly half of these participants chose TACE-based combination treatment as subsequent therapy after so-called TACE failure/refractoriness(n=88,46.1%).None of the existing TACE failure/refractoriness definitions were widely accepted by the participants;thus,it is necessary to re-define this concept for the treatment of HCC in China(n=235,91.4%).Most participants agreed that continuing TACE should be performed for patients with preserved liver function,presenting portal vein tumor thrombosis(n=242,94.2%)or extrahepatic spread(n=253,98.4%),after the previous TACE treatment to control intrahepatic lesion(s).Conclusions:There is an obvious difference in the recognition of TACE failure/refractoriness among Chinese clinicians based on existing definitions.Further work should be carried out to re-define TACE failure/refractoriness.

Subsequent Treatment after Transarterial Chemoembolization Failure/Refractoriness: A Review Based on Published Evidence

Transarterial chemoembolization(TACE)is widely applied for the treatment of hepatocellular carcinoma.Repeat TACE is often required in clinical practice because a satisfactory tumor response may not be achieved with a single session.However,repeated TACE procedures can impair liver function and increase treatment-related adverse events,all of which prompted the introduction of the concept of“TACE failure/refractoriness”.Mainly based on evidence from two retrospective studies conducted in Japan,sorafenib is recommended as the first choice for subsequent treatment after TACE failure/refractoriness.Several studies have investigated the outcomes of other subsequent treatments,including locoregional,other molecular targeted,anti-programmed death-1/anti-programed death ligand-1 therapies,and combination therapies after TACE failure/refractoriness.In this review,we summarize the up-to-date information about the outcomes of several subsequent treatment modalities after TACE failure/refractoriness.

Platelet transfusion refractoriness after T-cell-replete haploidentical transplantation is associated with inferior clinical outcomes

Haploidentical stem cell transplantation (haplo-SCT) has been an alternative source of bone marrow for patients without human leukocyte antigen (HLA)-matched donors. The aim of this study was to investigate the relationships between platelet transfusion refractoriness (PTR) and clinical outcomes in the setting of haplo-SCT. Between May 2012 and March 2014, 345 patients who underwent unmanipulated haplo-SCT were retrospectively enrolled. PTR occurred in 20.6% of all patients. Patients in the PTR group experienced higher transplant-related mortality (TRM, 43.7% vs. 13.5%, P<0.001), lower overall survival (OS, 47.9%vs. 76.3%, P<0.001) and lower leukemia-free survival (LFS, 47.9% vs. 72.3%, P<0.001) compared to patients in the non-PTR group. The multivariate analysis showed that PTR was associated with TRM (P=0.002), LFS (P<0.001), and OS (P<0.001).The cumulative incidences of PTR in patients receiving >12 platelet (PLT) transfusions (third quartile of PLT transfusions) were higher than in patients receiving either >6 (second quartile) or >3 (first quartile) PLT transfusions (56.1% vs. 41.6% vs. 28.2%,respectively; P<0.001). The multivariate analysis also showed that PTR was associated with the number of PLT transfusions(P<0.001). PTR could predict poor transplant outcomes in patients who underwent haploidentical SCT.

Corrosion behavior of co-gasification slag of furfural residue and coal on alumina-silica refractories

Gasification of furfural residue with coal can realize its efficient and clean utilization.But the high alkali metal content in furfural slag is easy to cause the corrosion of gasifier refractory.Two gasification coals with different silica alumina ratio and a furfural residue were selected in the study.The effects of furfural residue additions on corrosion of silica brick,corundum brick,high alumina brick and mullite brick were investigated by using XRD,SEM-EDS and Factsage Software,and the corrosion mechanism was analyzed.With increasing furfural residue addition,the permeability of the slags to high-aluminium-bearing refractories first decreases and then increases,while the permeability on silica brick shows a slight decrease trend.Leucite(KAlSi_(2)O_(6))with high-melting temperature is generated from the reaction of K_(2)O and SiO_(2)in slag with Al_(2)O_(3)in refractories after furfural residue is added,which hinders the infiltration of slag in refractories.Kaliophilite(KAlSiO_(4))of low-melting point is formed when K_(2)O content increases,and this contributes to the infiltration of slag in refractories.The acid-base reaction between slag and silica brick is distinctly occurred,more slag reacts with SiO_(2)in the silicon brick,resulting in a decrease in the amount of slag infiltrating into the silicon brick as furfural residue is added.The corrosion of silica brick is mainly caused by the acid-base reaction,while the corrosion of three alumina based refractory bricks of corundum,mullite and high alumina brick is determined by slag infiltration.A linear correlation between the percolation rate and slag viscosity is established,the slag permeability increases with decreasing viscosity,resulting in stronger permeability for the high Si/Al ratio slag with lower viscosity.

Spark plasma sintering of tungsten-based WTaVCr refractory high entropy alloys for nuclear fusion applications

W-based WTaVCr refractory high entropy alloys (RHEA) may be novel and promising candidate materials for plasma facing components in the first wall and diverter in fusion reactors. This alloy has been developed by a powder metallurgy process combining mechanical alloying and spark plasma sintering (SPS). The SPSed samples contained two phases, in which the matrix is RHEA with a body-centered cubic structure, while the oxide phase was most likely Ta2VO6through a combined analysis of X-ray diffraction (XRD),energy-dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The higher oxygen affinity of Ta and V may explain the preferential formation of their oxide phases based on thermodynamic calculations. Electron backscatter diffraction (EBSD) revealed an average grain size of 6.2μm. WTaVCr RHEA showed a peak compressive strength of 2997 MPa at room temperature and much higher micro-and nano-hardness than W and other W-based RHEAs in the literature. Their high Rockwell hardness can be retained to at least 1000°C.

Dexamethasone implant in naive versus refractory patients with diabetic macular edema:a Meta-analysis

AIM:To evaluate the efficacy and safety of the intravitreal dexamethasone implant in naive and refractory patients with diabetic macular edema(DME).METHODS:PubMed,Embase,Web of Science,and Medline databases were searched.The main outcomes were best-corrected visual acuity(BCVA)and central retinal thickness(CRT).The secondary outcomes included mean number of injections,intraoperative or postoperative complications including intraocular pressure(IOP)elevation and cataract.RESULTS:Ten comparative studies involving a total of 1000 DME eyes including 402 naive eyes and 598 refractory eyes were selected.The postoperative BCVA in the naive group was significantly better than in the refractory group[mean difference(MD)-0.11,95% confidence interval(CI)-0.17 to-0.05,P=0.0003;MD 8.69,95%CI 5.08 to 12.30,P<0.00001].Additionally,the naive group got greater improvement of BCVA change as well as more gains of BCVA letters than the refractory group[MD 7.71,95%CI 2.02 to 13.40,P=0.008;odds ratio(OR)2.99,95%CI 2.05 to 4.37,P<0.00001].The subgroup analysis revealed that the naive group had significantly higher BCVA gains of≥5,≥10,and≥15 letters compared to the refractory group(P=0.002,0.0001,0.003,respectively).No significant difference was detected between the two groups in either postoperative CRT(MD-22.36,95%CI-46.39 to 1.66,P=0.07)or the overall mean number of injections(MD-0.08,95%CI-0.38 to 0.22,P=0.61).Intraoperative and postoperative complications including the elevation of IOP(OR 0.47,95%CI 0.20 to 1.13,P=0.09)and cataract(OR 1.78,95%CI 0.97 to 3.24,P=0.06)showed no significant differences between the two groups during the follow-up time.CONCLUSION:Intravitreal dexamethasone implants for DME can improve anatomical and functional outcomes in both naive and refractory eyes and have a well-acceptable safety profile.Moreover,naive eyes maintain better visual outcomes than refractory eyes.It provides further evidence of better visual response when used for naive eyes as firstline therapy.

Road to recompensation:BavenoⅦcriteria and transjugular intrahepatic portosystemic shunt in liver cirrhosis

Liver cirrhosis has long been considered a point of no return,with limited hope for recovery.However,recent advancements,particularly the Baveno VII criteria and the utilization of transjugular intrahepatic portosystemic shunt(TIPS),have illuminated the concept of hepatic recompensation.In this editorial we comment on the article by Gao et al published in the recent issue.This editorial provides a comprehensive overview of the evolution of understanding cirrhosis,the criteria for recompensation,and the efficacy of TIPS in achieving recompensation.We discuss key findings from recent studies,including the promising outcomes observed in patients who achieved recompensation post-TIPS insertion.While further research is needed to validate these findings and elucidate the mechanisms underlying recompensation,the insights presented here offer renewed hope for patients with decompensated cirrhosis and highlight the potential of TIPS as a therapeutic option in their management.