Disease clearance in ulcerative colitis:A new therapeutic target for the future

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression.This has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic armamentarium.Subsequently,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal healing.While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures.Current recommendations lack consideration of histological healing.The simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully investigated.This has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.

Treat to target in Crohn’s disease:A practical guide for clinicians

A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.

Honeymoon phase in type 1 diabetes mellitus: A window of opportunity for diabetes reversal?

The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status.Not all individuals of T1DM progress in that specific sequence.We hereby present a case of T1DM with a classical third phase(honeymoon phase)and discuss the intri-cacies of this interesting phase along with a possible future promise of“cure”with the use of immunotherapies.We now know that the course of T1DM may not be in only one direction towards further progression;rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed.The third phase popularly called the“honeymoon phase”,is of special interest as this phase is complex in its pathogenesis.The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive“diabetes reversal”in T1DM.Identifying this phase is therefore the key,with a lot of varying criteria having been proposed.

Efficacy and safety of fecal microbiota transplantation for treatment of ulcerative colitis:A post-consensus systematic review and metaanalysis

BACKGROUND Numerous studies have assessed the efficacy and safety of fecal microbiota transplantation(FMT)as a therapy for ulcerative colitis(UC).However,the treatment processes and outcomes of these studies vary.AIM To evaluate the efficacy and safety of FMT for treating UC by conducting a systematic meta-analysis.METHODS The inclusion criteria involved reports of adult patients with UC treated with FMT,while studies that did not report clinical outcomes or that included patients with infection were excluded.Clinical remission(CR)and endoscopic remission(ER)were the primary and secondary outcomes,respectively.RESULTS We included nine studies retrieved from five electronic databases.The FMT group had better CR than the control group[relative risk(RR)=1.53;95%confidence interval(CI):1.19-1.94;P<0.0008].ER was statistically significantly different between the two groups(RR=2.80;95%CI:1.93-4.05;P<0.00001).Adverse events did not differ significantly between the two groups.CONCLUSION FMT demonstrates favorable performance and safety;however,well-designed randomized clinical trials are still needed before the widespread use of FMT can be recommended.Furthermore,standardizing the FMT process is urgently needed for improved safety and efficacy.

Remission of type 2 diabetes mellitus

The surge in type 2 diabetes mellitus(T2DM)is tightly linked to obesity,leading to ectopic fat accumulation in internal organs.Weight management has become a cornerstone of T2DM treatment,with evidence suggesting that significant weight loss can induce remission.Remission,defined as sustained hemoglobin(HbA1c)below 6.5% for at least 3 months without medication,can be achieved through various approaches,including lifestyle,medical,and surgical interventions.Metabolic bariatric surgery offers significant remission rates,particularly for patients with severe obesity.Intensive lifestyle modifications,including lowcalorie diets and exercise,have also demonstrated significant potential.Medications like incretin-based agents show robust results in improving beta-cell function,achieving glycemic control,and promoting weight loss.While complete remission without medication may not be attainable for everyone,especially those with severe insulin resistance or deficiency,early and aggressive glycemic control remains a crucial strategy.Maintaining HbA1c below 6.5%from the time of diagnosis reduces the risk of long-term complications and mortality.Moreover,considering a broader definition of remission,encompassing individuals with sustained control on medication,could offer a more comprehensive and inclusive approach to managing this chronic disease.

Advancements in autoimmune hepatitis management:Perspectives for future guidelines

The first-line treatment for autoimmune hepatitis involves the use of prednisone or prednisolone either as monotherapy or in combination with azathioprine(AZA).Budesonide has shown promise in inducing a complete biochemical response(CBR)with fewer adverse effects and is considered an optional first-line treatment,particularly for patients without cirrhosis;however,it is worth noting that the design of that study favored budesonide.A recent real-life study revealed higher CBR rates with prednisone when equivalent initial doses were administered.Current guidelines recommend mycophenolate mofetil(MMF)for patients who are intolerant to AZA.It is important to mention that the evidence supporting this recommendation is weak,primarily consisting of case series.Nevertheless,MMF has demonstrated superiority to AZA in the context of renal transplant.Recent comparative studies have shown higher CBR rates,lower therapeutic failure rates,and reduced intolerance in the MMF group.These findings may influence future guidelines,potentially leading to a significant modification in the first-line treatment of autoimmune hepatitis.Until recently,the only alternative to corticosteroids was lifelong maintenance treatment with AZA,which comes with notable risks,such as skin cancer and lymphoma.Prospective trials are essential for a more comprehensive assessment of treatment suspension strategies,whether relying on histological criteria,strict biochemical criteria,or a combination of both.Single-center studies using chloroquine diphosphate have shown promising results in significantly reducing relapse rates compared to placebo.However,these interesting findings have yet to be replicated by other research groups.Additionally,second-line drugs,such as tacrolimus,rituximab,and infliximab,should be subjected to controlled trials for further evaluation.

Diabetes remission and nonalcoholic fatty pancreas disease

This editorial focuses on the relationship between nonalcoholic fatty pancreas disease(NAFPD)and the development and remission of type 2 diabetes(T2D).NAFPD is characterized by intrapancreatic fatty deposition associated with obesity and not associated with alcohol abuse,viral infections,and other factors.Ectopic fat deposition in the pancreas is associated with the development of T2D,and the underlying mechanism is lipotoxicβ-cell dysfunction.However,the results on the relationship between intrapancreatic fat deposition(IPFD)andβ-cell function are conflicting.Regardless of the therapeutic approach,weight loss improves IPFD,glycemia,andβ-cell function.Pancreatic imaging is valuable for clinically monitoring and evaluating the management of T2D.

Correlation between type 2 diabetes mellitus remission and intrapancreatic fat deposition

BACKGROUND Intrapancreatic fat deposition(IPFD)exerts a significant negative impact on patients with type 2 diabetes mellitus(T2DM),accelerates disease deterioration,and may lead to impairedβ-cell quality and function.AIM To investigate the correlation between T2DM remission and IPFD.METHODS We enrolled 80 abdominally obese patients with T2DM admitted to our institution from January 2019 to October 2023,including 40 patients with weight lossinduced T2DM remission(research group)and 40 patients with short-term intensive insulin therapy-induced T2DM remission(control group).We comparatively analyzed improvements in IPFD[differential computed tomography(CT)values of the spleen and pancreas and average CT value of the pancreas];levels of fasting blood glucose(FBG),2-h postprandial blood glucose(2hPBG),and insulin;and homeostasis model assessment of insulin resistance(HOMA-IR)scores.Correlation analysis was performed to explore the association between T2DM remission and IPFD.RESULTS After treatment,the differential CT values of the spleen and pancreas,FBG,2hPBG,and HOMA-IR in the research group were significantly lower than those before treatment and in the control group,and the average CT value of the pancreas and insulin levels were significantly higher.Correlation analysis revealed that the greater the T2DM remission,the lower the amount of IPFD.

A Comprehensive Analysis of Efficacy and Safety of Probiotics in Inflammatory Bowel Disease

Introduction: Inflammatory bowel disease (IBD) affects approximately 7 million people worldwide. In the U.S. alone, per the CDC, 1.3% of adults, which is approximately 3,000,000 people, are diagnosed with inflammatory bowel disease-either, Crohn’s disease, or ulcerative colitis. The estimated cost of treatment can be close to $23,000 annually, with treatment regimens comprising biologic agents and anti-inflammatory therapies. Probiotics have recently gathered interest as a low-cost additional therapy option that, in addition to the current regimen of IBD management, allows for reductions in rates of IBD flare-ups by significantly reducing the number of emergency room visits and avoiding the need to constantly escalate treatment by addition of biologic agents in achieving remission. The Analysis Goal: Our research project aimed to see if there was a significant difference in the addition of probiotics to standard therapy in inflammatory bowel disease by comparing existing research studies and trials. We analyzed RCTs published in PubMed to assess the efficacy and safety of probiotics in patients with IBD in preventing frequent disease flare-ups and reducing the cost of care. Research Methods: We did a comparative analysis of available RCTs using a PubMed search and included studies that researched the addition of probiotic strains in patients with IBD (ulcerative colitis and Crohn’s disease). After reviewing the inclusion and exclusion criteria, the trials selected for analysis were reviewed by two independent reviewers. Results: We analyzed 21 RCTs, and 16 RCTs (76.2%) showed that probiotics are an effective therapy for IBD, inducing remission and reducing flare-up rates in patients on a standard treatment regimen. Conclusion: Probiotics given in combination with standard therapy in IBD are effective in decreasing disease activity rates and reducing remission rates. No significant adverse reactions to probiotics were noticed.

Treatment endpoints in ulcerative colitis:Does one size fit all?

A treat-to-target strategy in inflammatory bowel disease(IBD)involves treatment intensification in order to achieve a pre-determined endpoint.Such uniform and tight disease control has been demonstrated to improve clinical outcomes compared to treatment driven by a clinician’s subjective assessment of symptoms.However,choice of treatment endpoints remains a challenge in management of IBD via a treat-to-target strategy.The treatment endpoints for ulcerative colitis(UC),recommended by the Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)consensus have changed somewhat over time.The latest STRIDE-II consensus advises immediate(clinical response),intermediate(clinical remission and biochemical normalisation)and long-term treatment(endoscopic healing,absence of disability and normalisation of health-related quality of life,as well as normal growth in children)endpoints in UC.However,achieving deeper levels of remission,such as histologic normalisation or healing of the gut barrier function,may further improve outcomes among UC patients.Generally,all medical therapy should seek to improve short-and long-term mortality and morbidity.Hence treatment endpoints should be chosen based on their ability to predict for improvement in short-and long-term mortality and morbidity.Potential benefits of treatment intensification need to be weighed against the potential harms within an individual patient.In addition,changing therapy that has achieved partial response may lead to worse outcomes,with failure to recapture response on treatment reversion.Patients may also place different emphasis on certain potential benefits and harms of various treatments than clinicians,or may have strong opinions re certain therapies.Potential benefits and harms of therapies,incremental benefits of achieving deeper levels of remission,as well as uncertainties of the same,need to be discussed with individual patients,and a treatment endpoint agreed upon with the clinician.Future research should focus on quantifying the incremental benefits and risks of achieving deeper levels of remission,such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.focus on quantifying the incremental benefits and risks of achieving deeper levels of remission,such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.

Remission of type 2 diabetes mellitus:Emerging concepts and proposed diagnostic criteria

The remission of type 2 diabetes mellitus(T2DM)is a topic that has been widely discussed recently,and it gives new hope for people with T2DM.Achievement of normal blood glucose levels or levels below the diagnostic threshold for T2DM without pharmacotherapy among people with T2DM after metabolic surgery and carbohydrate or calorie-restricted diet paved the way for more enthusiastic research in this area.There is a lot of confusion regarding the appropriate terminology and definition of remission of T2DM.In this short review,we briefly analyzed the emerging concepts and proposed criteria for diagnosing remission of T2DM,which will be helpful for healthcare providers and people with T2DM.

Fecal microbiota transplantation for the maintenance of remission in patients with ulcerative colitis:A randomized controlled trial

BACKGROUND Fecal microbial transplantation(FMT)is a promising new method for treating active ulcerative colitis(UC),but knowledge regarding FMT for quiescent UC is scarce.AIM To investigate FMT for the maintenance of remission in UC patients.METHODS Forty-eight UC patients were randomized to receive a single-dose FMT or autologous transplant via colonoscopy.The primary endpoint was set to the maintenance of remission,a fecal calprotectin level below 200μg/g,and a clinical Mayo score below three throughout the 12-mo follow-up.As secondary endpoints,we recorded the patient’s quality of life,fecal calprotectin,blood chemistry,and endoscopic findings at 12 mo.RESULTS The main endpoint was achieved by 13 out of 24(54%)patients in the FMT group and by 10 out of 24(41%)patients in the placebo group(log-rank test,P=0.660).Four months after FMT,the quality-of-life scores decreased in the FMT group compared to the placebo group(P=0.017).In addition,the disease-specific quality of life measure was higher in the placebo group than in the FMT group at the same time point(P=0.003).There were no differences in blood chemistry,fecal calprotectin,or endoscopic findings among the study groups at 12 mo.The adverse events were infrequent,mild,and distributed equally between the groups.CONCLUSION There were no differences in the number of relapses between the study groups at the 12-mo follow-up.Thus,our results do not support the use of a single-dose FMT for the maintenance of remission in UC.

Successful lifestyle modifications may underlie umbilical cordmesenchymal stromal cell effects in type 2 diabetes mellitus

Type 2 diabetes mellitus(T2DM)is a lifelong condition and a grave threat to human health.Innovative efforts to relieve its detrimental effects are acutely needed.The sine qua non in T2DM management is consistent adherence to a prudent lifestyle and nutrition,combined with aerobic and resistance exercise regimens,together repeatedly shown to lead to complete reversal and even longterm remission.Non-adherence to the above lifestyle adjustments condemns any treatment effort and ultimately the patient to a grim fate.It is thus imperative that every study evaluating the effects of innovative interventions in T2DM objectively compares the novel treatment modality to lifestyle modifications,preferably through double-blind controlled randomization,before claiming efficacy.

Prognostic role of intestinal ultrasound in Crohn’s disease

The majority of patients affected by Crohn’s disease(CD)develop a chronic condition with persistent inflammation and relapses that may cause progressive and irreversible damage to the bowel,resulting in stricturing or penetrating complications in around 50%of patients during the natural history of the disease.Surgery is frequently needed to treat complicated disease when pharmacological therapy failes,with a high risk of repeated operations in time.Intestinal ultrasound(IUS),a non-invasive,cost-effective,radiation free and reproducible method for the diagnosis and follow-up of CD,in expert hands,allow a precise assessment of all the disease manifestations:Bowel characteristics,retrodilation,wrapping fat,fistulas and abscesses.Moreover,IUS is able to assess bowel wall thickness,bowel wall stratification(echo-pattern),vascularization and elasticity,as well as mesenteric hypertrophy,lymph-nodes and mesenteric blood flow.Its role in the disease evaluation and behaviour description is well assessed in literature,but less is known about the potential space of IUS as predictor of prognostic factors suggesting response to a medical treatment or postoperative recurrence.The availability of a low cost exam as IUS,able to recognize which patients are more likely to respond to a specific therapy and which patients are at high risk of surgery or complications,could be a very useful instrument in the hands of IBD physician.The aim of this review is to present current evidence about the prognostic role that IUS can show in predicting response to treatment,disease progression,risk of surgery and risk of post-surgical recurrence in CD.

Effectiveness of pharmacogenomics on the response and remission of treatment-resistant depression: a metaanalysis of randomised controlled trials

Background Pharmacogenomics(PGx)is a promising tool to realise tailored drug therapy for depression.Aims To investigate the treatment efficacy of PGxfor treatment-resistant depression(TRD)compared with treatmentas usual.Methods A systematic search was conducted in PubMed,Embase,the Cochrane Library,Web of Science and PsyclNFO to identify relevant studies published from inception to 15 April 2023.Two-arm randomised controlled trials(RCTs)exploring the efficacy of PGx-guided versus unguided treatment for TRD were included.The risk of bias in the included studies was evaluated using the Cochrane risk of bias assessment tool.The overall quality of evidence was assessed using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach.Results Seven RCTs(n=3003)comparing PGx-guided(n=1492)and unguided(n=1511)groups were identified and analysed.PGx-guided treatment was superior to treatment as usual in response(relative risk(RR)=1.31;95%confidence interval(95%Cl):1.15 to 1.49;p<0.001)and remission(RR=1.40;95%Cl:1.09 to 1.80;p=0.009)improvements.Effect sizes for acceptability(RR=0.90;95%Cl:0.80 to 1.02;p=0.100)and side effect burden(RR=0.58;95%Cl:0.29 to 1.15;p=0.120)between the two groups were not statistically different.The overall quality of evidence was rated from'very low'(25%)to low'(75%)based on the GRADE criteria.Conclusions PGx-guided treatment has shown a small overall effect in improving the response and remission rates for patients with TRD.However,these results should be interpreted cautiously because of the few included studies and the low quality of evidence.Further high-quality clinical trials are warranted to confirm the findings.

Spontanous Remission of PAN

Polyarteritis nodosa (PAN) affects mostly medium-sized arteries and sometimes small ones as well. The primary methods used to make the diagnosis are through physical examinations, biopsies of organs that are affected, and/or angiographic studies. Immunosuppressants like glucocorticoids and cyclophosphamide are usually started as soon as possible after a diagnosis. So, it’s not clear if sudden remission of PAN happens or not. Here we present a 42-year-old male who presented with right upper quadrant, right flank pain and fever. CT angiogram Aorta revealed soft tissue rind around the small to medium sized vessel in the abdomen and bilateral cortical renal infarcts of variable age in the right more than the left. A diagnosis of polyarteritis nodosa was made and the patient achieved spontaneous remission with no need for corticosteroids or immunosuppressive therapy.

Effect of Rituximab Versus Mycophenolate Mofetil or Cyclophosphamide as Control in Lupus Nephritis:A Meta-Analysis

Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.

Long-term remission by secukinumab in erythrodermic psoriasis with metabolic syndrome:report of two cases

Introduction Psoriasis is a chronic inflammatory systemic disorder which is strongly associated with metabolic syndrome.Erythrodermic psoriasis(EP)is a severe type of psoriasis that causes severe physical and mental impairment.Evidence-based data on EP treatment are limited in recent years.Although conventional systemic treatments such as acitretin,cyclosporine,methotrexate and steroids show efficacy in patients with EP,these treatments have many limitations and intolerance[1].Improvement of this syndrome can seriously affect patients’quality of life(DLQI).Secukinumab is an interleukin-17A inhibitor human monoclonal antibody which has been approved for the treatment of moderate to severe plaque psoriasis[2].There has been no research on the use of secukinumab in EP patients with metabolic syndrome.We present two EP patients with metabolic syndrome who achieved and maintained successful treatment and remission for more than 52 weeks with secukinumab.

小剂量干扰素合并联合化疗治疗白血病疗效观察

1 引言国外一般采用大剂量干扰素治疗白血病取得了明显的疗效。我科从1986年8月～1987年6月采用小剂量干扰素并用联合化疗治疗13例急性白血病取得较好的效果现报告如下。 2 资料与方法 2.1

精准治疗下恶性血液病微小残留病的临床价值

恶性血液病是一种严重危害人类健康的重点疾病,随着血液学的不断进步,联合化疗策略、特异性靶向治疗、造血干细胞移植技术的不断提高,使恶性血液病患者的生存状况得到了显著改善。但是,患者体内的肿瘤细胞负荷、肿瘤的原发耐药等诸多原因仍使部分患者在取得完全缓解（complete remission,CR）后会出现疾病复发,CR后复发是目前困扰恶性血液病治愈的难题之一。