Assessing disease activity using the pediatric Crohn’s disease activity index:Can we use subjective or objective parameters alone?

BACKGROUND The pediatric Crohn’s disease activity index(PCDAI)is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease.AIM To examine which items on the PCDAI drive assessment of disease activity,and how subgroups of subjective and objective items reflect change in disease state over time.METHODS Selective raw data from three prospectively collected datasets were combined,including 703 children with full PCDAI data at baseline,at 3-mo(Q1,n=670),and 1-year(Q4,n=474).Change in individual PCDAI scores from baseline to Q1 and to Q4 were examined using the non-weighted PCDAI.RESULTS Abdominal pain,well-being,weight,and stooling had the highest change scores over time.Objective indicators including albumin,abdominal exam,and height velocity followed.Change scores for well-being and abdominal exam did not explain significant variance at Q1 but were significant predictors at Q4(P<0.001 and P<0.05).Subjective and objective subgroups of items predicted less variance(18%and 22%)on total PCDAI scores at Q1 and Q4 compared to the full PCDAI,or a composite scale(both 32%)containing significant predictors.CONCLUSION Although subjective items on the PCDAI change the most over time,the full PCDAI or a smaller composite of items including a combination of subjective and objective components classifies disease activity better than a subgroup of either subjective or objective items alone.Reliance on subjective or objective items as stand-alone proxies for disease activity measurement could result in misclassification of disease state.

Impact of pain on health-related quality of life in patients with inflammatory bowel disease

AIM: To evaluate intensity, localization and cofactors of pain in Crohn’s disease and ulcerative colitis patients in connection with health-related quality of life (HRQOL) and disease activity. METHODS: We reviewed and analyzed the responses of 334 patients to a specifically designed questionnairebased on the short inflammatory bowel disease questionnaire (SIBDQ) and the German pain questionnaire. Pain intensity, HRQOL, Crohn’s disease activity index (CDAI) and colitis activity index (CAI) were correlated and verified on a visual analog scale (VAS). RESULTS: 87.9% of patients reported pain. Females and males reported comparable pain intensities and HRQOL. Surgery reduced pain in both genders (P = 0.023), whereas HRQOL only improved in females. Interestingly, patients on analgesics reported more pain (P = 0.003) and lower HRQOL (P = 0.039) than patients not on analgesics. A significant correlation was found in UC patients between pain intensity and HRQOL (P = 0.023) and CAI (P = 0.027), and in CD patients between HRQOL and CDAI (P = 0.0001), but not between pain intensity and CDAI (P = 0.35). No correlation was found between patients with low CDAI scores and pain intensity. CONCLUSION: Most IBD patients suffer from pain and have decreased HRQOL. Our study reinforces the need for effective individualized pain therapy in IBD patients.

Use of the ulcerative colitis endoscopic index of severity and Mayo endoscopic score for predicting the therapeutic effect of mesalazine in patients with ulcerative colitis

Objective:The ulcerative colitis endoscopic index of severity(UCEIS)and the Mayo endoscopic score(MES)are developed as objective methods of evaluating endoscopic severity in patients with ulcerative colitis(UC).The aim of this study is to investigate the diagnostic accuracy of the UCEIS and MES in predicting the patient's response to mesalazine.Methods:Consecutive patients with UC who had undergone colonoscopy within 1 month before starting mesalazine between October 2011 and July 2016 were retrospectively collected at the Department of Gastroenterology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine.The median follow-up was 81 months,and all the data were analyzed in January 2021.The primary outcome was the need for step-up treatment,which included the use of corticosteroids,immunomodulatory,or surgery during admission and follow-up.Data were analyzed using the c2 or Fisher exact test,Spearman test,t-test,and ManneWhitney U test.Results:Totally,65 patients were enrolled,of whom 12(18.5%)needed step-up treatment due to nonresponse to mesalazine.The UCEIS score,MES,and the ulcerative colitis disease activity index(UCDAI)score were significantly higher in patients who had nonresponse to mesalazine(UCEIS score:6.92±0.69 vs.4.45±1.17,p<0.001;MES:2.67±0.49 vs.2.15±0.69,p=0.024;UCDAI score:9.33±1.87 vs.6.70±2.38,p=0.002).In the multivariate analysis,the UCEIS score(OR=25.65,95%CI:3.048 e45.985,p=0.003),UCDAI score(OR=1.605,95%CI:1.144e2.254,p=0.006),and C-reactive protein level(OR=1.056,95%CI:1.006e1.108,p=0.026)were independent risk factors of nonresponse.The area under the ROC curve of UCEIS was 0.95,with a sensitivity of 100%and specificity of 84.6%,a cut-off value of 6,which outperformed the MES with an area under the ROC curve of 0.70.When the UCEIS score≥6,60%of patients eventually needed step-up treatment.Conclusions:The UCEIS is a useful instrument for predicting the therapeutic effect in patients with UC treated with mesalazine.The high probability of mesalazine treatment failure and benefits of other therapies should be discussed in patients with baseline UCEIS score≥6.

Role of capsule endoscopy in inflammatory bowel disease:Anything new?

Capsule endoscopy(CE)is a recently developed diagnostic method for diseases of the small bowel that is non-invasive,safe,and highly tolerable.Its role in patients with inflammatory bowel disease has been widely validated in suspected and established Crohn’s disease(CD)due to its ability to assess superficial lesions not detected by cross-sectional imaging and proximal lesions of the small bowel not evaluable by ileocolonoscopy.Because CE is a highly sensitive but less specific technique,differential diagnoses that can simulate CD must be considered,and its interpretation should be supported by other clinical and laboratory indicators.The use of validated scoring systems to characterize and estimate lesion severity(Lewis score,Capsule Endoscopy Crohn’s Disease Activity Index),as well as the standardization of the language used to define the lesions(Delphi Consensus),have reduced the interobserver variability in CE reading observed in clinical practice,allowing for the optimization of diagnoses and clinical management strategies.The appearance of the panenteric CE,the incorporation of artificial intelligence,magnetically-guided capsules,and tissue biopsies are elements that contribute to CE being a promising,unique diagnostic tool in digestive tract diseases.

Progress of ulcerative colitis patients during the COVID-19 pandemic

BACKGROUND We have previously demonstrated that the first wave of the coronavirus disease 2019(COVID-19)pandemic caused exacerbations in ulcerative colitis(UC)patients,probably through psychological and physical stress.However,successive waves of the COVID-19 pandemic continuously followed the first.The effects of this chronic stress on the disease condition in UC patients are of interest.AIM To clarify the effect of chronic stress from COVID-19 on disease condition in patients aggravated after the first wave.METHODS Our previous study investigated 289 consecutive UC outpatients treated in one center during March and April 2020,the period of the first wave of the COVID-19 pandemic.In this study,an identical group of 289 UC patients was evaluated using UC-disease activity index(UC-DAI),endoscopic mucosal appearance score,and Matts pathological grade scoring.RESULTS Of the 289 UC patients included in the study in 2020,10 patients dropped out as of 2021 and another 11 patients dropped out as of 2022,making three groups for 2020,2021 and 2022.No significant differences in characteristics were found among the three groups.UC-DAI scores had aggravated during the period of the first wave of the COVID-19 pandemic,but significantly recovered in 2021 and remained stable in 2022.Matts grade scores significantly recovered in 2021 from those in 2020 and remained stable in 2022.CONCLUSION Disease activity of UC patients recovered in 2021 and remained stable in 2022,aggravated by the stress of the first wave of COVID-19 in 2020 despite persistence of the pandemic.

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.

Low dose oral curcumin is not effective in induction of remission in mild to moderate ulcerative colitis: Results from a randomized double blind placebo controlled trial

AIM To evaluate the role of oral curcumin in inducing clinical remission in patients with mild to moderate ulcerative colitis(UC).METHODS A prospective randomized double-blind placebo-controlled trial comparing the remission inducing effect of oral curcumin and mesalamine 2.4 g with placebo and mesalamine 2.4 g in patients of ulcerative colitis with mild to moderate severity was conducted from January 2003 to March 2005. The included patients received 1 capsule thrice a day of placebo or curcumin(150 mg) for 8 wk. Patients were evaluated clinically and endoscopically at 0,4 and 8 wk. The primary outcome was clinical remission at 8 wk and secondary outcomes were clinical response, mucosal healing and treatment failure at 8 wk. The primary analysis was intention to treat worst case scenario(ITT-WCS).RESULTS Of 300 patients with UC, 62 patients(curcumin: 29, placebo: 33) fulfilled the inclusion criteria and were randomized at baseline. Of these, 21 patients did not complete the trial, 41 patients(curcumin: 16, placebo: 25) finally completed 8 wk. There was no significant difference in rates of clinical remission(31.3% vs 27.3%, P = 0.75), clinical response(20.7% vs 36.4%, P = 0.18), mucosal healing(34.5% vs 30.3%, P = 0.72), and treatment failure(25% vs 18.5%, P = 0.59) between curcumin and placebo at 8 wk.CONCLUSION Low dose oral curcumin at a dose of 450 mg/d was ineffective in inducing remission in mild to moderate cases of UC.

Endoscopic ultrasonography in the evaluation of condition and prognosis of ulcerative colitis

BACKGROUND Ulcerative colitis(UC)is usually diagnosed through histopathology,enteroscopy,clinical symptoms,and physical findings;however,it is difficult to accurately evaluate disease severity.AIM To investigate the value of endoscopic ultrasonography(EUS)in the evaluation of the severity and prognosis of UC.METHODS Patients with UC who were seen in our hospital from March 2019 to December 2020 were eligible,and disease severity was evaluated according to the modified Truelove and Witts and Mayo scores.We performed EUS,calculated the UC endoscopic index of severity(UCEIS)and EUS-UC scores,and administered appropriate treatment.The UCEIS and EUS-UC scores of patients were assessed in relation to disease severity,and the correlations between UCEIS and EUS-UC scores and disease severity was also analyzed.The UCEIS and EUS-UC scores before and after treatment were also compared.RESULTS A total of 79 patients were included in this study.According to the Mayo Index,23,32,and 24 patients had mild,moderate and severe UC,respectively.The UCEIS and EUS-UC scores were higher in moderate cases(4.98±1.04 and 5.01±0.99,respectively)than in mild cases(1.56±0.82 and 1.64±0.91,respectively,P<0.05).Furthermore,the UCEIS and EUS-UC scores(7.31±1.10 and 7.59±1.02,respectively)were higher in severe cases than in moderate cases(P<0.05).According to the modified Truelove and Witts scores,21,36,and 22 patients were classified as having mild,moderate and severe disease,respectively.The UCEIS and EUS-UC scores were significantly higher in moderate disease(4.79±1.11 and 4.96±1.23,respectively)than in mild disease(1.71±0.78 and 1.69±0.88,respectively,P<0.05).Additionally,the UCEIS and EUS-UC scores in severe disease(7.68±1.22 and 7.81±0.90,respectively)were significantly higher than in moderate disease(P<0.05).The UCEIS and EUSUC scores were significantly and positively correlated with disease severity according to the modified Truelove and Witts score and Mayo score(P<0.05).The UCEIS and EUS-UC scores after 2 mo of treatment(3.88±0.95 and 4.01±1.14,respectively)and after 6 mo of treatment(1.59±0.63 and 1.64±0.59,respectively)were lower than the respective scores before treatment(5.93±1.79 and 6.04±2.01)(P<0.05).CONCLUSION EUS can clarify the status of UC and accurately evaluate the treatment response,providing an objective basis for formulation and adjustment of the treatment plan.

Perianal fistulodesis–A pilot study of a novel minimally invasive surgical and medical approach for closure of perianal fistulae

BACKGROUND Perianal fistulae strongly impact on quality of life of affected patients.AIM To challenge and novel minimally invasive treatment options are needed.METHODS Patients with Crohn’s disease(CD)in remission and patients without inflammatory bowel disease(non-IBD patients)were treated with fistulodesis,a method including curettage of fistula tract,flushing with acetylcysteine and doxycycline,Z-suture of the inner fistula opening,fibrin glue instillation,and Zsuture of the outer fistula opening followed by post-operative antibiotic prophylaxis with ciprofloxacin and metronidazole for two weeks.Patients with a maximum of 2 fistula openings and no clinical or endosonographic signs of a complicated fistula were included.The primary end point was fistula healing,defined as macroscopic and clinical fistula closure and lack of patient reported fistula symptoms at 24 wk.RESULTS Fistulodesis was performed in 17 non-IBD and 3 CD patients,with a total of 22 fistulae.After 24 wk,all fistulae were healed in 4 non-IBD and 2 CD patients(overall 30%)and fistula remained closed until the end of follow-up at 10-25 mo.In a secondary per-fistula analysis,7 out of 22 fistulae(32%)were closed.Perianal disease activity index(PDAI)improved in patients with fistula healing.Low PDAI was associated with favorable outcome(P=0.0013).No serious adverse events were observed.CONCLUSION Fistulodesis is feasible and safe for perianal fistula closure.Overall success rates is at 30%comparable to other similar techniques.A trend for better outcomes in patients with low PDAI needs to be confirmed.

Immune checkpoint inhibitor-associated arthritis in advanced pulmonary adenocarcinoma:A case report

BACKGROUND With the wide application of immune checkpoint inhibitors(ICIs)in cancer treatment,immune-related adverse events occur frequently,involving almost all organs and systems.The incidence of ICI-associated arthritis(IA)is unknown.In most cases,IA is not serious and non-lethal.Higher checkpoint inhibitor arthritis disease activity may be associated with cancer progression.Here,we report a severe case of IA with high arthritis disease activity in advanced pulmonary adenocarcinoma,causing permanent withdrawal of pembrolizumab,but the patient remained in complete remission(CR)20 mo after the development of IA.CASE SUMMARY An 81-year-old smoking man was admitted to our hospital because of left chest pain for 9 mo.He was finally diagnosed with advanced pulmonary adenocarcinoma,with programmed cell death 1 ligand 1 expression of 70%.The patient responded to pembrolizumab treatment and achieved CR,but IA occurred after the 5th cycle of pembrolizumab administration.Although non-steroidal antiinflammatory drugs and disease-modifying anti-rheumatic drugs were prescribed,arthralgia and joint swelling occurred.The symptoms of arthritis were further aggravated when immunotherapy was given again after short-term withdrawal.Clinical Disease Activity Index(CDAI)score,a traditional measure of arthritis activity,was 43.Intravenous methylprednisolone was prescribed at 20 mg/d and then tapered over the subsequent 4 wk.The symptoms of arthritis steadily improved and completely resolved 4 mo after withdrawal of pembrolizumab.A recent follow-up in June 2022 revealed satisfactory clinical recovery of arthritis and the patient remained in CR.CONCLUSION This case report highlights that early recognition of IA and appropriate treatment are critical to improving the outcome of both ICI-arthritis and lung cancer.

Vitamin D therapy in pediatric patients with inflammatory bowel disease:a systematic review and meta-analysis

Background There is some evidence for the role of vitamin D deficiency in the pathogenesis of inflammatory bowel disease(IBD)in the pediatric population.However,the results are contradictory.Therefore,we have conducted a systematic review and meta-analysis to evaluated the effect of vitamin D on pediatric patients with IBD.Methods We carried out a systematic search in databases from inception until 20 January 2022.We included all relevant articles that evaluate the efficacy and safety of vitamin D on disease activity,inflammatory factors,and vitamin D and calcium levels in pediatric patients with IBD.Random effects models were used to combine the data.The main outcomes were then analyzed using weight mean difference(WMD)and respective 95%confidence interval(CI).Results Fifteen treatment arms met the eligibility criteria and were included.Pooled estimates indicated that intervention with vitamin D has a significantly beneficial effect on 25-hydroxy vitamin D3[25(OH)D3](pooled WMD of 17.662 ng/mL;CI 9.77-25.46;P<0.001),calcium(pooled WMD of 0.17 mg/dL;CI 0.04-0.30;P=0.009),and inflammatory factors including C-reactive protein(CRP)(pooled WMD of-6.57 mg/L;CI-11.47 to-1.67;P=0.009)and erythrocyte sedimentation rate(ESR)(pooled WMD of-7.94 mm/h;CI-12.65 to-3.22;P=0.001)levels.In addition,this effect was greater for vitamin D levels at doses greater than 2000 IU,and when follow-up duration was more than 12 weeks.Conclusion This study showed that vitamin D therapy can have a significant and beneficial effect on 25(OH)D3,calcium,and inflammatory factors in children and adolescents with IBD.

Qingchi San(青赤散)treats ulcerative colitis in mice by inhibiting the nuclear factor-kappa B signaling pathway and Nucleotide-binding oligomerization domain,leucine-rich repeat and pyrin domain-containing 3 inflammasome formation

OBJECTIVE:To investigate the efficacy of Qingchi San(青赤散,QCS),a preparation of Traditional Chinese Medicine,on ulcerative colitis(UC)in mice by inhibiting the nuclearfactor-kappa B(NF-κB)signaling pathway and nucleotide-binding oligomerization domain,leucine-rich repeat and pyrin domain-containing 3(NLRP3)inflammasome formation.METHODS:The UC model was established with male C57BL/6J as the animal model.Bodyweight,Disease Activity Index(DAI),colon length and weight were detected.Furthermore,colonic histology was performed by hematoxylin-eosin(HE)staining.interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),myeloperoxidase(MPO)and superoxide dismutase(SOD)were performed by enzyme-linked immunosorbent assay.Cyclooxygenase 2(COX2)and inducible nitric oxide synthase(iNOS)mRNA expression were conducted by real-time quantitative polymerase chain reaction(RT-qPCR).NF-κB,inhibitor of NF-κBα(iκBα),Phosphorylated inhibitor of NF-κBα(p-iκBα),caspase-1,NLRP3 and Apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)protein expression were conducted by Western blotting.RESULTS:Compared with UC model group,Bodyweight was significantly increased in QCS treatment.At the same time,DAI was significantly decreased in QCS treatment.Colon length and weight and colonic histology were significantly improved in QCS treatment.Furthermore,the expression of IL-1β,IL-6,TNF-α,MPO,SOD,COX2,and iN OS were significantly decreased in QCS treatment.Finally,the expression of NF-κB signaling pathway-related proteins NF-κB,iκBα,p-iκBα,and the expression of NLRP3 inflammasome related proteins caspase-1,NLRP3 and ASC were significantly decreased in QCS treatment.CONCLUSION:Traditional Chinese drug QCS could treat UC by inhibiting the NF-κB signaling pathway and NLRP3 inflammasome formation in mice.

维多珠单抗治疗慢性抗生素难治性储袋炎

背景:慢性抗生素难治性储袋炎(CARP)是回肠储袋-肛管吻合术(IPAA)的一个并发症,治疗上存在巨大挑战。维多珠单抗是一种肠道选择性的抗α4β7整合素单克隆抗体,现已应用于CARP患者,但其疗效数据报道不多。本研究旨在评估维多珠单抗作为诱导治疗,应用于CARP患者的有效性和安全性。方法:从一个单中心的历史队列中,筛选出2015年1月至2017年6月间接受维多珠单抗治疗的CARP患者。病例纳入标准:改良储袋疾病严重指数(mPDAI)评分≥5的急性储袋炎;但如果没有mPDAI评分则以临床医生作出急性储袋炎的诊断为准。于治疗前及治疗后3个月,通过储袋镜和门诊检查来进行mPDAI评分。结果:19例患者纳入研究,平均年龄(26.7612.8)岁,其中男性10例(53%)。9例(47%)在结肠切除术前曾接受抗肿瘤坏死因子(TNF)药物治疗,10例(53%)患者在IPAA术后接受过抗TNF药物治疗。维多珠单抗治疗后,6例(32%)患者mPDAI症状评分显著改善(P=0.031);14例(74%)患者mPDAI内镜评分和总评分均显著改善,中位下降均为2分(P=0.031)。仅2例(11%)患者出现药物不良反应,另有4例(21%)患者需针对CARP行再次手术治疗。结论:本研究显示,维多珠单抗治疗CARP患者安全有效。而这些结果尚需更大样本量的研究证实。