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.

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.

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.

Investigation of Microstructure and Phase Composition of Chromic Oxide, AZS/Cr and High-alumina Refractories after Exposure of Basalt and Aluminaboronsilicate Glasses Melts

The microstructure and phase composition of high-alumina,chromic oxide,and AZS/Cr refractories containing 30%and 60%(by mass)Cr_(2)O_(3) after exposure to aluminaboronsilicate glasses and basalt melts depending on the type of melts and temperature have been studied.The mechanisms of refractory corrosion by the used melts and the factors contributing to the inhibition of corrosion development have been investigated by the method of petrographic analysis.On the basis of obtained results,the use of high-alumina,chromic oxide,and AZS/Cr refractories in the sections of glass furnace linings,experiencing the intensive impact of aluminaboronsilicate glasses and basalt melts,has been confirmed and scientifically substantiated.

Refractory ulcerative colitis:Upadacitinib versus other biologics

In this editorial we comment on an article published in World Journal of Clinical Cases in 2024,in which a case of refractory ulcerative colitis(UC)was discussed based on the response to different lines of biologics.Different studies showed that different classes of biologics have their advantages and disadvantages in the treatment of refractory UC.Certain classes are superior to others and if tried earlier on would lead to a possible change in the outcome.

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.

Investigation of Refractory Bricks and Oxide Materials Heated in Hydrogen Reduction Conditions

This study aims to provide the basic knowledge for furnace refractory design by investigating refractory property changes occurred in a hydrogen atmosphere.Since refractory bricks are thermodynamically stable in a hydrogen atmosphere at 1100°C,we tried to find out the minute changes.In this experiment,a refractory brick was prepared by andalusite,mullite chamotte,and clay as raw materials and heated to 1100°C in a 100%hydrogen atmosphere for 72 h.It was found that the strength of the brick was decreased and the color was changed to black by the reduction of impurities.And in addition,this study covered research on the slaking risk of MgO raw materials because the minimum temperature is expected to 400°C in fluidized reduction furnaces unlike shaft furnaces.

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.

The 9^(th) International Symposium on Refractories

Organizedby The Chinese Society for Metals The Chinese Ceramic Society Sinosteel Luoyang Institute of Refractories Research Co.,Ltd.Sponsored by Refractories Committee of The Chinese Society for Metals Sinosteel Luonai Materials Technology Corporation Co-Sponsoredby State Key Laboratory of Advanced Refractories The State Key Laboratory of Refractories and Metallurgy Refractories Press Indian Refractory Makers Association The Federation for International Refractory Research and Education.

Glaucoma drainage device implantation and cyclophotocoagulation in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty

AIM:To compare the surgical outcomes of glaucoma drainage device implantation(GDI)and trans-scleral neodymium:YAG cyclophotocoagulation(CPC)in the management of refractory glaucoma after Descemetstripping automated endothelial keratoplasty(DSAEK).METHODS:This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery(15 with GDI and 14 with CPC).The main outcome measures were intraocular pressure(IOP),glaucoma surgery success rate(defined as IOP of 6–21 mm Hg without additional anti-glaucoma operation),number of glaucoma medications,endothelial graft status,and best-corrected visual acuity(BCVA).RESULTS:The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries,both for the GDI and CPC groups.Both groups showed significant IOP reduction after glaucoma surgery.The GDI group presented a significantly higher success rate in IOP control than the CPC group(60%vs 21.4%,P=0.03).Both procedures significantly decreased the number of glaucoma medications(P=0.03).Forty percent and 57%of cases in the GDI and the CPC group,respectively,experienced endothelial graft failure during follow-up(P=0.36).Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group.CONCLUSION:Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK.GDI is preferable to CPC in refractory glaucoma cases after DSAEK,as it manifests a significantly higher success rate for IOP control,similar endothelial graft failure rate,and relatively preserves BCVA than CPC.

The Role of the Size Effect on the Drying of Refractory Castables—How Its Under-standing Could Narrow the Gap between Laboratory Studies and Industrial Reality

Refractories have unique capabilities such as sustaining their shape and properties at extreme conditions such as the combination of high temperatures and thermal shock,contact with molten metals and slags and in some circumstances resistance to erosion from abrasive particles.Given the large processing output of the heavy industries such as the cement and steel ones which both require high temperature processes,the refractories structures span various meters and weight of several tons.As the water removal stage of hydraulic bonded castables in industrial sites takes hours(10-60 h)due to the risk of explosive spalling,efforts to mitigate it are commonly studied.This has provided theoretical understanding of the general aspects of drying and important tools,such as the thermogravimetry analysis(TGA),for the design of refractory compositions with higher explosive spalling resistance.However,the optimization of this process is still far from the industrial reality especially because the actual linings that require the drying are orders of magnitude larger than the samples considered in the laboratory tests.Therefore,this study proposed the analysis of the sample volume effect on the water removal dynamics through TGA of high alumina castables with calcium aluminate cement.Conventionalφ5 cm×5 cm cylindrical samples were assessed in a laboratory scale equipment whereas macro TGA were carried out considering 20 cm×20 cm×20 cm and 30 cm×30 cm×30 cm cubic samples.Additionally,the effect of polymeric fibers was also considered.It was found out that the different thermal gradients within the macro TGA samples resulted in an inflection on the sample’s heating rate and that the mass loss was affected by the volume considered,especially for the composition without additives.These findings highlight the requirement of carefully taking into consideration the different dimensional sizes and thermal gradients in the samples when analyzing and interpreting the laboratory studies,and especially when trying to extrapolate such results to the industrial reality.

Thermomechanical Modelling of Industrial Vessels that Contain Refractory Masonry Linings

Some refractory linings that protect metallic vessels from the hot temperature of the products they contain are made of masonries with or without mortar.The joints play an important role,reducing the stresses in the masonries during heating.Furthermore,the presence of these joints makes the behaviour of the masonry nonlinear and orthotropic.To perform a thermomechanical simulation using a finite element method of an industrial vessel that contains hundreds or thousands of bricks and joints,microscopic models are not suitable due to the high computational time and the management of the behaviour of the joints(opening/closing)which affects the convergence.To overcome these problems,it is proposed to replace the masonry by a homogeneous material that has a behaviour equivalent to the set of bricks and joints,using a periodic homogenization technique.Since the joints can be closed or open,the equivalent material will have a different behaviour according to the joint state.Furthermore,refractory materials have an elastic-viscoplastic behaviour at high temperatures.So,the equivalent material will have an orthotropic elastic-viscoplastic behaviour,requiring a nonlinear homogenisation technique.An overview of this approach developed at University of Orléans is presented with two industrial applications(blast-furnace and steel ladle).

Sporadic gastrinoma with refractory benign esophageal stricture:A case report

BACKGROUND Gastrinoma is characterized by an excessive release of gastrin,leading to hypersecretion of gastric acid,subsequently resulting in recurrent peptic ulcers,chronic diarrhea,and even esophageal strictures.This case report aims to improve awareness and facilitate early diagnosis and treatment of gastrinoma by presenting a rare case of gastrinoma with refractory benign esophageal stricture(RBES).Additionally,it highlights the persistent challenges that gastroenterologists encounter in managing RBES.CASE SUMMARY This case demonstrates a patient with gastrinoma who developed RBES and complete esophageal obstruction despite management with maximal acid suppressive therapy,multiple endoscopic bougie dilations and endoscopic incisional therapy(EIT).CONCLUSION It is essential to diagnose gastrinoma as early as possible,as inadequately controlled acid secretion over an extended period increases the risk of developing severe esophageal strictures.In patients with esophageal strictures causing complete luminal obstruction,blind reopening EIT presents challenges and carries a high risk of perforation.

Intermittent melena and refractory anemia due to jejunal cavernous lymphangioma:A case report

BACKGROUND Lymphangiomas in the gastrointestinal tract are extremely rare in adults.As a benign lesion,small intestine lymphangiomas often remain asymptomatic and pose challenges for definitive diagnosis.However,lymphangiomas can give rise to complications such as abdominal pain,bleeding,volvulus,and intussusception.Here,we report a case of jejunal cavernous lymphangioma that presented with intermittent melena and refractory anemia in a male adult.CASE SUMMARY A 66-year-old man presented with intermittent melena,fatigue and refractory anemia nine months prior.Esophagogastroduodenoscopy and colonoscopy were performed many times and revealed no apparent bleeding.Conservative management,including transfusion,hemostasis,gastric acid secretion inhibition and symptomatic treatment,was performed,but the lesions tended to recur shortly after surgery.Ultimately,the patient underwent capsule endoscopy,which revealed a more than 10 cm lesion accompanied by active bleeding.After singleballoon enteroscopy and biopsy,a diagnosis of jejunal cavernous lymphangioma was confirmed,and the patient underwent surgical resection.No complications or recurrences were observed postoperatively.CONCLUSION Jejunal cavernous lymphangioma should be considered a cause of obscure gastrointestinal bleeding.Capsule endoscopy and single-balloon enteroscopy can facilitate diagnosis.Surgical resection is an effective management method.

New therapeutic strategy with extracorporeal membrane oxygenation for refractory hepatopulmonary syndrome after liver transplant: A case report

BACKGROUND Due to the lack of published literature about treatment of refractory hepatopulmonary syndrome(HPS)after liver transplant(LT),this case adds information and experience on this issue along with a treatment with positive outcomes.HPS is a complication of end-stage liver disease,with a 10%-30%incidence in cirrhotic patients.LT can reverse the physiopathology of this process and restore normal oxygenation.However,in some cases,refractory hypoxemia persists,and extracorporeal membrane oxygenation(ECMO)can be used as a rescue therapy with good results.CASE SUMMARY A 59-year-old patient with alcohol-related liver cirrhosis and portal hypertension was included in the LT waiting list for HPS.He had good liver function(Model for End-Stage Liver Disease score 12,Child-Pugh class B7).He had pulmonary fibrosis and a mild restrictive respiratory pattern with a basal oxygen saturation of 82%.The macroaggregated albumin test result was>30.Spirometry demonstrated a forced expiratory volume in one second(FEV1)of 78%,forced vital capacity(FVC)of 74%,FEV1/FVC ratio of 81%,diffusion capacity for carbon monoxide of 42%,and carbon monoxide transfer coefficient of 57%.He required domiciliary oxygen at 2 L/min(16 h/d).The patient was admitted to the intensive care unit(ICU)and extubated in the first 24 h,needing high-flow therapy and non-invasive ventilation and inhaled nitric oxide afterwards.Reintubation was needed after 72 h.Due to the non-response to supportive therapies,installation of ECMO was decided with progressive recovery after 9 d.Extubation was possible on the tenth day,maintaining a high-flow nasal cannula and de-escalating to conventional oxygen therapy after 48 h.He was discharged from ICU on postoperative day(POD)20 with a 90%-92%oxygen saturation.Steroid recycling was needed twice for acute rejection.The patient was discharged from hospital on POD 27 with no symptoms,with an 89%-90%oxygen saturation.CONCLUSION Due to the favorable results observed,ECMO could become the central axis of treatment of HPS and refractory hypoxemia after LT.

A Case of Diabetic Nephropathy with Refractory Gastroparesis and Review of the Literature

Background: Gastroparesis is one of the complications of diabetes mellitus, and long-term gastroparesis seriously affects patients quality of life. Most of the patients can be relieved after lifestyle improvement and medication, but refractory gastroparesis is difficult to relieve, and is still a challenge in clinical treatment. Aim: To report a case of a patient with diabetic nephropathy combined with refractory gastroparesis, and to analyse the mechanism, diagnosis, severity grading, treatment of refractory gastroparesis in conjunction with a review of the literature, and to investigate the causes of recurrent nausea and vomiting in diabetic nephropathy patients with refractory diabetic gastroparesis and the possible effective treatment options. Case Presentation: The patient was hospitalised for recurrent nausea and vomiting and diagnosed with diabetic nephropathy and gastroparesis. Symptoms recurred after medication and peritoneal dialysis, and the patients symptoms were relieved after multifaceted interventions. Conclusion: Diabetic nephropathy and refractory gastroparesis can both manifest as digestive tract symptoms, and in the face of this complex disease, it is necessary to analyse the various etiological factors and take comprehensive treatment measures.

Performance Assessment on Corrosion Resistance of Refractory Materials Based on High-temperature Machine Vision Technology

Refractory materials,as the crucial foundational materials in high-temperature industrial processes such as metallurgy and construction,are inevitably subjected to corrosion and penetration from high-temperature media during their service.Traditionally,observing the in-situ degradation process of refractory materials in complex high-temperature environments has presented challenges.Post-corrosion analysis are commonly employed to assess the slag resistance of refractory materials and understand the corrosion mechanisms.However,these methods often lack information on the process under the conditions of thermal-chemical-mechanical coupling,leading to potential biases in the analysis results.In this work,we developed a non-contact high-temperature machine vision technology by the integrating Digital Image Correlation(DIC)with a high-temperature visualization system to explore the corrosion behavior of Al2O3-SiO2 refractories against molten glass and Al2O3-MgO dry ramming refractories against molten slag at different temperatures.This technology enables realtime monitoring of the 2D or 3D overall strain and average strain curves of the refractory materials and provides continuous feedback on the progressive corrosion of the materials under the coupling conditions of thermal,chemical,and mechanical factors.Therefore,it is an innovative approach for evaluating the service behavior and performance of refractory materials,and is expected to promote the digitization and intelligence of the refractory industry,contributing to the optimization and upgrading of product performance.

Manufacture of Industrial Refractory Crucibles Based on Clays from Burkina Faso

In Burkina Faso, one of the three largest gold producers in West Africa, foundry activity is often paralyzed when basic equipment such as crucibles and cups are not available or should be imported. However, previous studies have shown the availability of kaolinite-rich clay resources that could be used for the local manufacture of silico-aluminous ceramic crucibles. This work allowed to manufacture industrial ceramic crucibles with local clays and then they were tested in foundry industry. The materials were manufactured from three (03) raw materials including two clays (SAB and ROU) and sand. The chemical and mineral analysis has shown that the raw materials are suitable for the formulation of refractory materials. The results of characterization of the materials formulated showed that the properties of use are appreciable. The porosity of the materials is relatively low (23 - 28 vol%) with a diametral compressive strength between 0.61 and 1.34 MPa. Crucibles sintered at 1250˚C with a stay of 2 hours have a mechanical strength capable of supporting the weight of the ores contained. These crucibles have a refractoriness under load (T0.5) above 1141˚C and resist chemical attacks. Tests were carried out in the industry at 1100˚C, and the results were satisfactory.

Microwave-assisted Synthesis of Al_(4)SiC_(4) and Its Effect on Properties of MgO-C Refractories

Al_(4)SiC_(4) was synthesized from Al powder, silicon carbide, and graphite by microwave sintering, and characterized by XRD and SEM. Then the synthesized material was added to the magnesia carbon refractory brick to study its effect on the oxidation resistance, apparent porosity, bulk density, elastic modulus, and modulus of rupture. It is found that Al_(4)SiC_(4) can be synthesized by microwave sintering at 1 300 ℃ and the addition of Al_(4)SiC_(4)-containing material as an antioxidant can enhance the oxidation resistance of the magnesia carbon refractory brick.

Refractory Ventricular Fibrillation with Underlying Coronary Artery Disease after COVID-19 Vaccine-Kounis Syndrome or Coincidence

A 63-year-old man with diabetes and asymptomatic coronary artery disease developed refractory ventricular arrhythmia at 20 hours at rest after his second COVID-19 vaccine. Despite significant stenosis in the coronary arteries, there was no evidence of acute or old myocardial infarction, heart failure, myocarditis or structural abnormalities on post-mortem to account for the substrate for the fatal arrhythmia. The refractory and incessant nature of the ventricular fibrillation and post-mortem finding of a grossly elevated unexplained IgE level (in the absence of acute myocardial infarction) suggested the possibility of Kounis Syndrome or allergic acute coronary syndrome.