A novel solution treatment and aging for powder bed fusion-laser beam Ti-6Al-2Sn-4Zr-6Mo alloy:Microstructural and mechanical characterization

Ti-6Al-4Zr-2Sn-6Mo alloy is one of the most recent titanium alloys processed using powder bed fusion-laser beam(PBF-LB)technology.This alloy has the potential to replace Ti-6Al-4V in automotive and aerospace applications,given its superior mechanical properties,which are approximately 10%higher in terms of ultimate tensile strength(UTS)and yield strength after appropriate heat treatment.In as-built conditions,the alloy is characterized by the presence of soft orthorhombicα″martensite,necessitating a postprocessing heat treatment to decompose this phase and enhance the mechanical properties of the alloy.Usually,PBFed Ti6246 components undergo an annealing process that transforms theα″martensite into anα-βlamellar microstructure.The primary objective of this research was to develop a solution treatment and aging(STA)heat treatment tailored to the unique microstructure produced by the additive manufacturing process to achieve an ultrafine bilamellar microstructure reinforced by precipitation hardening.This study investigated the effects of various solution temperatures in theα-βfield(ranging from 800 to 875℃),cooling media(air and water),and aging time to determine the optimal heat treatment parameters for achieving the desired bilamellar microstructure.For each heat treatment condition,differentα-βmicrostructures were found,varying in terms of theα/βratio and the size of the primaryα-phase lamellae.Particular attention was given to how these factors were influenced by increases in solution temperature and how microhardness correlated with the percentage of the metastableβphase present after quenching.Tensile tests were performed on samples subjected to the most promising heat treatment parameters.A comparison with literature data revealed that the optimized STA treatment enhanced hardness and UTS by13%and 23%,respectively,compared with those of the annealed alloy.Fracture surface analyses were conducted to investigate fracture mechanisms.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

Mechanism of cryorolling and aging treatment for enhancing corrosion properties of 2195 Al−Li alloy

The impact of cryorolling(CR)and room temperature rolling(RTR)followed by artificial aging on the corrosion characteristics of 2195 Al−Li alloy(AA2195)was studied.Transmission electron microscope,scanning electron microscope,optical microscope,intergranular corrosion experiment,and electrochemical experiment were used.Throughout different stages of aging treatment,the corrosion behavior of both CR and RTR samples exhibited a sequential progression of pitting corrosion,followed by intergranular corrosion,and then pitting corrosion again.The corrosion rates of both samples initially showed an increase,followed by a gradual stabilization over time.The size and density of T1 phase significantly influenced the corrosion performance of the alloy.During the peak aging and over-aging stages,the CR sample exhibited superior corrosion resistance to the RTR sample,attributed to its finer T1 phase.

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Clinicopathological features and treatment of gastrointestinal schwannomas

BACKGROUND Gastrointestinal schwannomas(GIS)are rare neurogenic tumors arising from Schwann cells in the gastrointestinal tract.Studies on GIS are limited to small case reports or focus on specific tumor sites,underscoring the diagnostic and thera-peutic challenges they pose.AIM To comprehensively examine the clinical features,pathological characteristics,treatment outcomes,associated comorbidities,and prognosis of GIS.METHODS The study population included patients diagnosed with GIS at the First Affiliated Hospital,Zhejiang University School of Medicine,between June 2007 and April 2024.Data were retrospectively collected and analyzed from medical records,including demographic characteristics,endoscopic and imaging findings,treatment modalities,pathological evaluations,and follow-up information.RESULTS In total,229 patients with GIS were included,with a mean age of 56.00 years and a male-to-female ratio of 1:1.83.The mean tumor size was 2.75 cm,and most(76.9%)were located in the stomach.Additionally,6.6%of the patients had other malig-nant tumors.Preoperative imaging and endoscopy frequently misdiagnosed GIS as gastrointestinal stromal tumors.However,accurate preoperative diagnosis was achieved using endoscopic ultrasound-guided fine-needle aspiration combined with immunohistochemical analysis,in which S100 and SOX-10 markers were mostly positive.Smaller tumors were typically managed with endoscopic resection,while larger lesions were treated with surgical resection.Follow-up results showed that most patients experienced favorable outcomes.CONCLUSION Preoperative diagnosis of GIS via clinical characteristics,endoscopy,and imaging examinations remains challenging but crucial.Endoscopic therapy provides a minimally invasive and effective option for patients.

Scalable Ir‑Doped NiFe_(2)O_(4)/TiO_(2) Heterojunction Anode for Decentralized Saline Wastewater Treatment and H_(2) Production

Wastewater electrolysis cells(WECs)for decentralized wastewater treatment/reuse coupled with H_(2) production can reduce the carbon footprint associated with transportation of water,waste,and energy carrier.This study reports Ir-doped NiFe_(2)O_(4)(NFI,~5 at%Ir)spinel layer with TiO_(2) overlayer(NFI/TiO_(2)),as a scalable heterojunction anode for direct electrolysis of wastewater with circumneutral pH in a single-compartment cell.In dilute(0.1 M)NaCl solutions,the NFI/TiO_(2) marks superior activity and selectivity for chlorine evolution reaction,outperforming the benchmark IrO_(2).Robust operation in near-neutral pH was confirmed.Electroanalyses including operando X-ray absorption spectroscopy unveiled crucial roles of TiO_(2) which serves both as the primary site for Cl−chemisorption and a protective layer for NFI as an ohmic contact.Galvanostatic electrolysis of NH4+-laden synthetic wastewater demonstrated that NFI/TiO_(2)not only achieves quasi-stoichiometric NH_(4)^(+)-to-N_(2)conversion,but also enhances H_(2)generation efficiency with minimal competing reactions such as reduction of dissolved oxygen and reactive chlorine.The scaled-up WEC with NFI/TiO_(2)was demonstrated for electrolysis of toilet wastewater.

Treatment of thymoma with low-dose glucocorticoids before surgery for significant tumor shrinkage: A case report

BACKGROUND Thymic epithelial neoplasms are rare malignant neoplasms originating in the thymus gland.There have been case reports of patients with advanced thymomas treated with a methylprednisolone pulse or with glucocorticoid(GCs)shock be-fore surgery,followed by surgical treatment,all of whom achieved good results.The effect of GCs on thymomas is related mainly to the action on GC receptors in thymic lymphocytes and epithelial cells.GC receptor expression has been asso-ciated with a better prognosis in patients with thymomas,including those with surgically removed thymomas.CASE SUMMARY We report a case of a patient with thymoma who had a significant response to preoperative low-dose GC therapy.A mediastinal tumor was detected in the patient via computerized tomography upon admission.The tumor was initially suspected to be a thymic tumor,but lymphoma could not be ruled out.The tumor shrank significantly after low-dose(5 mg/day)GC therapy.Thoracoscopic thy-moma resection was performed after puncture pathology was confirmed.The patient recovered well after the operation and is currently performing well with no recurrence of the tumor.CONCLUSION This case highlights that low-dose GCs are effective in the treatment of thymomas,and we believe that GCs should be applied more frequently and studied more thoroughly in the treatment of thymomas.

Pancreatic primitive neuroectodermal tumors:Clinical features,treatment,and influencing factors

BACKGROUND Data on clinical characteristics,treatment outcomes,and prognosis of pancreatic primitive neuroectodermal tumors(PNETs)are limited.AIM To analyze the clinical data of 30 patients with pancreatic PNETs to identify their clinical characteristics and factors associated with prognosis.METHODS We used the keywords"primary neuroectodermal tumor,""digestive tract,""pancreas,""pancreatic,"and"gastrointestinal,"individually or in combination,to collect data from a global database for all patients with pancreatic PNET to date.Univariate and Cox regression analyses were performed to identify prognostic factors for patient survival.RESULTS A total of 30 cases of pancreatic PNET were included in this study:15 males and 15 females with a mean age of 24 years.The main symptom was abdominal pain(73.3%),and the median tumor size was 7.85 cm.Twenty-four patients(80.0%)underwent surgery and nineteen patients received adjuvant therapy.Local metastasis was observed in 13 patients(43.3%),lymph node metastasis in 10 patients(33.3%),and distant metastasis in 6 patients(20.0%).Local recurrence was observed in 13 patients(43.3%).The median survival time of all patients was 29.4 months,and the overall estimated 1-year and 3-year survival rates were approximately 66.0%and 36.4%,respectively.Univariate analysis showed that chemotherapy(P=0.036),local metastasis(P=0.041),lymph node metastasis(P=0.003),distant metastasis(P=0.049),and surgical margins(P=0.048)were the prognostic factors affecting survival.Multivariate analysis revealed only lymph node metastasis(P=0.012)as a prognostic factor.CONCLUSION Pancreatic PNET is extremely rare,occurs in young adults,has no apparent sex predisposition,has a high rate of metastasis and early recurrence,and has a very poor prognosis.The diagnosis of pancreatic PNET requires a combination of clinical symptoms,pathologic features,immunohistochemistry,and cytogenetic analysis.Univariate analysis suggested that chemotherapy,metastasis,and surgical margins were prognostic factors affecting survival,and multivariate analysis suggested that lymph node metastasis is an important prognostic factor.Therefore,early diagnosis,early and extensive resection,and adjuvant chemoradiotherapy may help improve prognosis.

Advances in radiotherapy in the treatment of esophageal cancer

Recent advancements in radiotherapy for esophageal cancer have significantly improved treatment outcomes and patient quality of life.Traditional radiotherapy techniques have been enhanced by the integration of advanced imaging and precision targeting technologies,such as intensity-modulated radiotherapy and proton therapy,which allow for more accurate tumor targeting while minimizing damage to surrounding healthy tissues.Additionally,combining radiotherapy with immunotherapy has shown promising results,leveraging the body’s im-mune response to enhance the effectiveness of cancer treatment.Studies have also highlighted the benefits of neoadjuvant chemoradiation followed by surgical resection,which has been associated with improved overall survival rates com-pared to radiotherapy alone.These innovations are paving the way for more effe-ctive and personalized treatment strategies,offering new hope for patients with esophageal cancer.

Risk factors,monitoring,and treatment strategies for early recurrence after rectal cancer surgery

Early recurrence(ER)following surgery for rectal cancer is a significant factor impacting patient survival rates.Tsai et al identified age,preoperative neoadjuvant therapy,length of hospital stay,tumour location,and pathological stage as factors influencing the risk of ER.Postoperative monitoring for ER should encompass a thorough medical history review,physical examination,tumour marker testing,and imaging studies.Additionally,noninvasive circulating tumour cell DNA testing can be utilized to predict ER.Treatment strategies may involve radical surgery,radiation therapy,chemotherapy,and immunotherapy.Through a comprehensive analysis of risk factors,the optimization of monitoring methods,and the development of personalized treatment strategies,it is anticipated that both the efficacy of treatment and the quality of life for rectal cancer patients with postoperative recurrence can be significantly improved.

Addressing social function in the treatment of depression:A call for holistic approaches

This article discusses the importance of addressing social functioning impairment in patients with residual depressive symptoms,as highlighted in the study by Liao et al.The authors showed that social dysfunction persists in many patients despite symptom remission.This observation calls for a shift in depression treatment strategies,with an emphasis on integrating social functioning as a key treatment goal.This article suggests targeted interventions that focus on both symptomatic relief and the restoration of social function.

Isletβ-cell function preservation by different anti-diabetic treatments in Chinese elderly patients with type 2 diabetes mellitus

BACKGROUND The preservation of isletβ-cell function in elderly patients with type 2 diabetes mellitus(T2DM)is a top priority for diabetic control.AIM To assess the preservation of isletβ-cell function among elderly Chinese patients with T2DM after different anti-diabetic treatments.METHODS In this longitudinal observational study,elderly patients with T2DM treated with insulin,oral antidiabetic drugs or a combination of both were enrolled to disclose their isletβ-cell function between baseline and follow-up.Isletβ-cell function was determined by the plasma Homeostasis Model forβ-cell function(HOMA-β),Cpeptide and area under the curve(AUC)based on oral glucose tolerance test.Changes inβ-cell function(decrement or increment from baseline)between different therapy groups were the outcomes.RESULTS In total,745 elderly patients(≥60 years)with T2DM[insulin monotherapy,n=105;oral anti-diabetic drugs(OAD)monotherapy,n=321;insulin plus OAD,n=319]had their baseline and follow-upβ-cell function assessed during a median observation period of 4.5 years(range,3.0-7.2 years).Overall,isletβ-cell function(HOMA-β,fasting Cpeptide,fasting insulin,AUCc-pep,AUCins,AUCc-pep/AUCglu,AUCins/AUCglu)consistently deteriorated over time regardless of the three different antidiabetic treatments.No statistical differences in decrement were observed among the three groups regarding the isletβ-cell function indices.All three groups showed an increased ratio of delayed insulin secretion response after 4.5 years of observation.CONCLUSION In Chinese elderly patients with T2DM,isletβ-cell function progressively declines regardless of insulin supplement or insulin plus OAD treatments.

Early and accurate diagnosis and selection of appropriate treatment plans are crucial for patients with gastrointestinal hemangiomas

Gastrointestinal hemangioma(GIH)is clinically rare,accounting for 7%-10%of benign gastrointestinal tumors and 0.5%of systemic hemangiomas.GIH can occur as either solitary or multiple lesions,with gastrointestinal bleeding as a significant clinical manifestation.Understanding the clinical and endoscopic features of GIH is essential for improving diagnostic accuracy,particularly through endoscopy and selective arteriography,which are highly effective in diagnosing GIH and preventing misdiagnosis and inappropriate treatment.Upon confirmed diagnosis,it is essential to thoroughly evaluate the patient's condition to determine the most suitable treatment modality—whether surgical,endoscopic,or minimally invasive intervention.The minimally invasive interventional partial embolization therapy using polyvinyl alcohol particles,proposed and implemented by Pospisilova et al,has achieved excellent clinical outcomes.This approach reduces surgical trauma and the inherent risks of traditional surgical treatments.

Diagnosis and treatment of bipolar disorder in Phelan-McDermid syndrome:A case report and review of literature

BACKGROUND Phelan-McDermid syndrome(PMS)is a rare genetic disorder characterized by intellectual disability,delayed language development,autism spectrum disorders,motor tone abnormalities,and a high risk of psychiatric symptoms,including bipolar disorder.CASE SUMMARY This report presented an 18-year clinical history of a 36-year-old woman with PMS,marked by intellectual disabilities,social withdrawal,and stereotyped behaviors.Diagnosed with bipolar disorder at the age of 18 years old,she encountered significant treatment challenges,including severe adverse reactions to antipsychotic medications in 2022,which led to speech and functional regression.Through rehabilitation and comprehensive therapy,her condition gradually improved.In 2024,after further treatment,her symptoms stabilized,highlighting the complexities and successes of long-term management.CONCLUSION Effective management of PMS requires a thorough clinical history,genetic testing,and long-term supportive care.

Insight into the efficacy and safety of pirfenidone: The treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)has a poor prognosis if left untreated;therefore,early treatment with pirfenidone is crucial.Lei et al conducted a retrospective analysis to evaluate the effectiveness of early pirfenidone treatment on lung function in 113 patients with IPF.In addition to other research,pirfeni-done has demonstrated efficacy in patients at all stages of IPF once correct diagnosis has been made.In advanced IPF,we include the requirement for pirfenidone.Therefore,it is essential to choose an appropriate method of adminis-tration method,such as inhalation.This may circumvent the drawbacks of the high cost and possible adverse effects of this drug.

Model tests and numerical analysis of emergency treatment of cohesionless soil landslide with quick-setting polyurethane

Shotcrete is one of the common solutions for shallow sliding.It works by forming a protective layer with high strength and cementing the loose soil particles on the slope surface to prevent shallow sliding.However,the solidification time of conventional cement paste is long when shotcrete is used to treat cohesionless soil landslide.The idea of reinforcing slope with polyurethane solidified soil(i.e.,mixture of polyurethane and sand)was proposed.Model tests and finite element analysis were carried out to study the effectiveness of the proposed new method on the emergency treatment of cohesionless soil landslide.Surcharge loading on the crest of the slope was applied step by step until landslide was triggered so as to test and compare the stability and bearing capacity of slope models with different conditions.The simulated slope displacements were relatively close to the measured results,and the simulated slope deformation characteristics were in good agreement with the observed phenomena,which verifies the accuracy of the numerical method.Under the condition of surcharge loading on the crest of the slope,the unreinforced slope slid when the surcharge loading exceeded 30 k Pa,which presented a failure mode of local instability and collapse at the shallow layer of slope top.The reinforced slope remained stable even when the surcharge loading reached 48 k Pa.The displacement of the reinforced slope was reduced by more than 95%.Overall,this study verifies the effectiveness of polyurethane in the emergency treatment of cohesionless soil landslide and should have broad application prospects in the field of geological disasters concerning the safety of people's live.

Clinical features of abnormalα-fetoprotein in 15 patients with chronic viral hepatitis B after treatment with antiviral drugs

BACKGROUND Liver function of chronic hepatitis B(CHB)patients is essentially normal after treatment with antiviral drugs.In rare cases,persistently abnormally elevatedα-fetoprotein(AFP)is seen in CHB patients following long-term antiviral treatment.However,in the absence of imaging evidence of liver cancer,a reasonable expla-nation for this phenomenon is still lacking.AIM To explore the causes of abnormal AFP in patients with CHB who were not diag-nosed with liver cancer.METHODS From November 2019 to May 2023,15 patients with CHB after antiviral treatment and elevated AFP were selected.Clinical data and quality indicators related to laboratory testing,imaging data,and pathological data were obtained through inpatient medical records.RESULTS All patients had increased AFP and significantly elevated IgG.Cancer was excluded by imaging examination.Only four patients had elevated alanine ami-notransferase,10 had elevated aspartate aminotransferase,nine had elevated total bilirubin,and two had antinuclear antibodies.The liver biopsy and histopatho-logical examination indicated that 14 patients had rosette,moderate,or higher interfacial inflammation,lymphocyte infiltration,and severe hepatic fibers(11 cases),which was consistent with the pathological features of autoimmune hepa-titis(AIH).After 8-12 week of hormone therapy,the levels of AFP and IgG,and liver function returned to normal(P<0.05).CONCLUSION For patients with CHB and elevated AFP after antiviral treatment,autoimmune hepatitis should be considered.CHB with AIH is clinically insidious and difficult to detect,and prone to progression to cirrhosis.Liver puncture pathological examination should be performed when necessary to confirm diagnosis.

Multimodal treatment combining neoadjuvant therapy,laparoscopic subtotal distal pancreatectomy and adjuvant therapy for pancreatic neck-body cancer:Case series

BACKGROUND Pancreatic cancer involving the pancreas neck and body often invades the retroperitoneal vessels,making its radical resection challenging.Multimodal treatment strategies,including neoadjuvant therapy,surgery,and postoperative adjuvant therapy,are contributing to a paradigm shift in the treatment of pancreatic cancer.This strategy is also promising in the treatment of pancreatic neckbody cancer.AIM To evaluate the feasibility and effectiveness of a multimodal strategy for the treatment of borderline/locally advanced pancreatic neck-body cancer.METHODS From January 2019 to December 2021,we reviewed the demographic characteristics,neoadjuvant and adjuvant treatment data,intraoperative and postoperative variables,and follow-up outcomes of patients who underwent multimodal treatment for pancreatic neck-body cancer in a prospectively collected database of our hospital.This investigation was reported in line with the Preferred Reporting of Case Series in Surgery criteria.RESULTS A total of 11 patients with pancreatic neck-body cancer were included in this study,of whom 6 patients were borderline resectable and 5 were locally advanced.Through multidisciplinary team discussion,all patients received neoadjuvant therapy,of whom 8(73%)patients achieved a partial response and 3 patients maintained stable disease.After multidisciplinary team reassessment,all patients underwent laparoscopic subtotal distal pancreatectomy and portal vein reconstruction and achieved R0 resection.Postoperatively,two patients(18%)developed ascites,and two patients(18%)developed pancreatic fistulae.The median length of stay of the patients was 11 days(range:10-15 days).All patients received postoperative adjuvant therapy.During the follow-up,three patients experienced tumor recurrence,with a median disease-free survival time of 13.3 months and a median overall survival time of 20.5 months.CONCLUSION A multimodal treatment strategy combining neoadjuvant therapy,laparoscopic subtotal distal pancreatectomy,and adjuvant therapy is safe and feasible in patients with pancreatic neck-body cancer.

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.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.