Can serum immunoglobulin G4 levels and age serve as reliable predictors of relapse in autoimmune pancreatitis?

We are writing in response to the paper published in the World Journal of Gastroenterology by Zhou et al.The authors identified higher serum immunoglobulin(Ig)G4 levels and age over 55 years as independent risk factors for disease relapse.Despite notable strengths,it is crucial to address potential biases.Firstly,the cohort study included 189 patients with autoimmune pancreatitis(AIP)type 1(with higher IgG4 seropositivity and higher relapse)and 24 with type 2(with lower IgG4 seropositivity and lower relapse).Consequently,most,if not all,AIP type 2 patients were assigned to the normal group,possibly inflating the association of higher serum IgG4 levels with relapse and potentially exaggerating the association of older age with relapse.Secondly,the authors did not provide sufficient details regarding AIP diagnosis,such as the ratio of definitive vs probable cases and the proportion of biopsies.In cases where histological evidence is unavailable or indeterminate,AIP type 2 may be misdiagnosed as definitive type 1,and type 1 may also be misdiagnosed as probable type 2,particularly in cases with normal or mildly elevated serum IgG4 levels.Lastly,in this retrospective study,approximately one-third of the consecutive patients initially collected were excluded for various reasons.Accordingly,the impact of nonrandom exclusion on relapse outcomes should be carefully considered.In conclusion,the paper by Zhou et al offers plausible,though not entirely compelling,evidence suggesting a predictive role of elevated serum IgG4 levels and advanced age in AIP relapse.The foundation for future investigations lies in ensuring a reliable diagnosis and accurate disease subtyping,heavily dependent on obtaining histological specimens.In this regard,endoscopic ultrasound-guided fine-needle biopsy emerges as a pivotal component of the diagnostic process,contributing to mitigating biases in future explorations of the disease.

Dengue causing relapse of minimal change disease: A double-edged sword

Dengue virus infection is endemic in India with seasonal variations.It can lead to lethal consequences with plasma leakage and/or bleeding[1,2].Dengue shock syndrome has high mortality in developing countries like India.Dengue can cause functional proteinuria and even heavy proteinuria[3-6].Though dengue has been implicated to cause glomerulonephritis[7],to the best of our knowledge,dengue as a cause of relapse of minimal change disease(MCD)has not been reported.

Statistical evaluation of cluster formation of relapse in neuromyelitis optica spectrum disorder

Evaluating the cluster formation of clinical attacks in chronic relapsing diseases is an important statistical issue because the presence of attack clusters may influence therapeutic strategies for relapse prevention.We recently reported the occurrence of unevenly clustered attacks in patients with anti-aquaporin-4(AQP4)antibody-positive neuromyelitis optica spectrum disorder(NMOSD)(Akaishi et al.,2020a).

Long-term complete response to anti-programmed-death-1 monotherapy in a patient with relapsed and refractory ovarian adenocarcinoma: A case report

BACKGROUND Ovarian cancer is the most common malignant tumor of the female reproductive system,and the survival rate of patients with relapsed and refractory ovarian cancer is very low.CASE SUMMARY Here,we report a case of high-grade serous papillary adenocarcinoma of the ovary that was successfully treated with immunotherapy.Radical surgery and adjuvant chemotherapy for the 56-year-old patient were successful;however,her tumor relapsed.Subsequent second-line chemotherapy,targeted agents,and other treatments were ineffective,as the tumor continued to recur and metastasize.Anti-programmed cell death-1(PD-1)monotherapy(tislelizumab)completely alleviated the tumor,and the multiple metastatic tumors disappeared.To date,the patient has used anti-PD-1 for 32 months,experiencing no disease progression and maintaining good health without additional treatment.CONCLUSION This case suggests that anti-PD-1 immunotherapy may have long-term positive effects on outcomes in some refractory recurrent solid tumors.Further research is needed to identify patients most likely to respond to anti-PD-1 therapy.

Cyclops syndrome following anterior cruciate ligament reconstruction: Can relapse occur after surgery?

Symptomatic cyclops lesions are complications that can be seen at rates of up to approximately 10%after anterior cruciate ligament reconstruction.However,recurrent cyclops lesions have rarely been documented.There are case rare series in the literature regarding the treatment of recurrent cyclops lesion.Future large studies are needed to investigate factors contributing to the development of cyclops lesions and syndrome and treatment options.

Comparison of fecal calprotectin levels and endoscopic scores for predicting relapse in patients with ulcerative colitis in remission

BACKGROUND Although the usefulness of endoscopic scores,such as the Mayo Endoscopic Subscore(MES),Ulcerative Colitis Endoscopic Index of Severity(UCEIS),and Ulcerative Colitis Colonoscopic Index of Severity(UCCIS),and biomarkers such as fecal calprotectin(FC)for predicting relapse in ulcerative colitis(UC)has been reported,few studies have included endoscopic scores for evaluating the entire colon.AIM To compare the usefulness of FC value and MES,UCEIS,and UCCIS for predicting relapse in patients with UC in clinical remission.METHODS In total,75 patients with UC in clinical and endoscopic remission who visited our institution between February 2019 and March 2022 were enrolled.The diagnosis of UC was confirmed based on the clinical presentation,endoscopic findings,and histology,according to the current established criteria for UC.Fecal samples were collected the day before or after the colonoscopy for measurement of FC.Endoscopic evaluations were performed using MES,UCEIS,and UCCIS.The primary outcome measure of this study was the assessment of the association between relapse within 12 mo and MES,UCEIS,UCCIS,and FC.The secondary outcome was the comparison between endoscopic scores and biomarkers in en-rolled patients with UC with mucosal healing.RESULTSFC and UCCIS showed a significant correlation with UCEIS (r = 0.537, P < 0.001 and r = 0.957, P < 0.001, respectively).Receiver-operating characteristic analysis for predicting MES 0 showed that the area under the curve ofUCCIS was significantly higher than that of FC (P < 0.01). During the 1-year observation period, 18 (24%) patientsexperienced a relapse, and both the FC and UCCIS of the relapse group were significantly higher than that of theremission group. The cut-off values for predicting relapse were set at FC = 323 mg/kg and UCCIS = 10.2. The areaunder the curve of the receiver-operating characteristic analysis for predicting relapse did not show a significantdifference between FC and UCCIS. The accuracy of the endoscopic scores and biomarkers in predicting relapse was86.7% for UCCIS, 85.3% for UCEIS, 76.0% for FC, and 73.3% for MES.CONCLUSIONThe three endoscopic scores and FC may predict UC relapse during clinical remission. Among these scores, UCEISmay be the most useful in terms of ease of evaluation and accuracy.

Multiple evanescent white dot syndrome relapse following BNT162b2 mRNA COVID-19 vaccination

Dear Editor,We report a case of multiple evanescent white dot syndrome(MEWDS)relapse following mRNA corona virus disease 2019(COVID-19)vaccination.MEWDS is a choroidal inflammatory disease belonging to the group of“white dot syndromes”group,with an excellent prognosis[1].MEWDS is usually idiopathic,but there have been reports of MEWDS following viral infection or vaccination[1-2].

Identification of multiple risk factors for colorectal cancer relapse after laparoscopic radical resection

BACKGROUND Colorectal cancer(CRC)is a common life-threatening disease that often requires surgical intervention,such as laparoscopic radical resection.However,despite successful surgeries,some patients experience disease relapse.Identifying the risk factors for CRC relapse can help guide clinical interventions and improve patient outcomes.AIM To determine the risk factors that may lead to CRC relapse after laparoscopic radical resection.METHODS We performed a retrospective analysis using the baseline data of 140 patients with CRC admitted to our hospital between January 2018 and January 2020.All included participants were followed up until death or for 3 years.The baseline data and laboratory indicators were compared between the patients who experienced relapse and those who did not experienced relapse.RESULTS Among the 140 patients with CRC,30 experienced relapse within 3 years after laparoscopic radical resection and 110 did not experience relapse.The relapse group had a higher frequency of rectal tumors with low differentiation and lymphatic vessel invasion than that of the non-relapse group.The expression of serum markers and the prognostic nutritional index were lower,whereas the neutrophil-to-lymphocyte ratio,expression of cytokeratin 19 fragment antigen 21-1,vascular endothelial growth factor,and Chitinase-3-like protein 1 were significantly higher in the relapse group than those in the non-relapse group.The groups did not differ significantly based on other parameters.Logistic regression analysis revealed that all the above significantly altered factors were independent risk factors for CRC relapse.CONCLUSION We identified multiple risk factors for CRC relapse following surgery,which can be considered for the clinical monitoring of patients to reduce disease recurrence and improve patient survival.

Neglected and Relapsed Clubfoot in Adults, the Functional Outcome of Acute Surgical Correction

Background: Neglected clubfoot in this series is defined as untreated equino-cavo-adducto-varus in older children or adults. Relapsed clubfoot is the residual deformity that remains after single or multiple surgical interventions. Severely neglected clubfoot rarely exists today in developed countries, except in some emigrants from low- and middle-income countries. Acute surgical management with corrective mid-foot osteotomy and elongation of the Achilles tendon has an excellent functional outcome. Objective: To assess the functional outcome of acute correction of neglected Talipes-quinoa-varus deformity in adults. Methods: This is a cross-sectional, hospital–based multi-centric study. Forty patients were included in this study. Midfoot osteotomy and elongation of the Achilles tendon were performed on all patients. Data was collected using a questionnaire and the functional outcome has been assessed using the American Orthopedic Foot and Ankle Society Score (AOFAS). This score was measured before surgery and one year after surgery. Results: the mean age was 19.9 ± 4.7 years. Males were 25 (62.5%) and females were 15 (37.5%). The mean preoperative AOFAS score was 37.7 ± 7.1 (poor). This score improved to 80.7 ± 13.7 (good to excellent), two years after surgery. However, this indicates a significant change in the functional outcome after the operation (p value Conclusion: acute correction of neglected and relapsed TEV with elongation of the Achilles tendon and single midfoot osteotomy has excellent functional outcome as assessed by AOFAS Score. The satisfaction with this procedure is impressive. The younger age population showed better outcomes with this procedure.

Implantation of hydrogel-liposome nanoplatform inhibits glioblastoma relapse by inducing ferroptosis

Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults.However,the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment.Ferroptosis is a recently discovered form of iron-dependent cell death that may have excellent prospect as chemosensitizer.The utilization of ferropotosis inducer Erastin could significantly mediate chemotherapy sensitization of Temozolomide and exert anti-tumor effects in glioblastoma.In this study,a combination of hydrogel-liposome nanoplatform encapsulatedwith Temozolomide and ferroptosis inducer Erastin was constructed.Theαvβ3 integrin-binding peptide cyclic RGD was utilized to modify codelivery system to achieve glioblastoma targeting strategy.As biocompatible drug reservoirs,cross-linked GelMA(gelatin methacrylamide)hydrogel and cRGD-coated liposome realized the sustained release of internal contents.In the modified intracranial tumor resection model,GelMA-liposome system achieved slow release of Temozolomide and Erastin in situ for more than 14 d.The results indicated that nanoplatform(T+E@LPs-cRGD+GelMA)improved glioblastoma sensitivity to chemotherapeutic temozolomide and exerted satisfactory anti-tumor effects.It was demonstrated that the induction of ferroptosis could be utilized as a therapeutic strategy to overcome drug resistance.Furthermore,transcriptome sequencing was conducted to reveal the underlying mechanism that the nanoplatform(T+E@LPs-cRGD+GelMA)implicated in.It is suggested that GelMA-liposome system participated in the immune response and immunomodulation of glioblastoma via interferon/PD-L1 pathway.Collectively,this study proposed a potential combinatory therapeutic strategy for glioblastoma treatment.

Using machine learning to identify factors related to nitrous oxide(laughing gas)relapse among adolescents

Introduction Nitrous oxide(N2O/laughing gas)has been used in medical practice as an inhalational anaesthetic and analgesic for more than 150 years.1 In the past decades,N2O exhibited increasing popularity among recreational drug users for its euphoric effects,potentially through its interaction with the endogenous opioid system.2 Recreational use of N2O emerged as the seventh most used drug globally in the past decade.3 The use of N2O can cause myelopathy,myocardial injury,anaemia,severe mood disorders,sensory and motor neuropathy,and psychotic symptoms.45 Prolonged N2O intake results in vitamin B12 deficiency and inhibits methionine synthetase,folate and DNA production,leading to plasma homocysteine(HCY)level elevation and bone marrow haematopoietic dysfunction.6 This study aimed to investigate the neurological symptoms of nitrous oxide use and then explore the relapse trajectory and risk factors for relapse.

Relapsed primary extraskeletal osteosarcoma of liver:A case report and review of literature

BACKGROUND Extraskeletal osteosarcoma(ESOS)is a highly malignant osteosarcoma that occurs in extraskeletal tissues.It often affects the soft tissues of the limbs.ESOS is classified as primary or secondary.Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient,which is very rare.CASE SUMMARY Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient.The patient had a giant cystic-solid mass in the right hepatic lobe that was evident on ultrasound and computed tomography.Postoperative pathology and immunohistochemistry of the mass,which was surgically removed,suggested fibroblastic osteosarcoma.Hepatic osteosarcoma reoccurred 48 d after surgery,resulting in significant compression and narrowing of the hepatic segment of the inferior vena cava.Consequently,the patient underwent stent implantation in the inferior vena cava and transcatheter arterial chemoembolization.Unfortunately,the patient died of multiple organ failure postoperatively.CONCLUSION ESOS is a rare mesenchymal tumor with a short course and a high likelihood of metastasis and recurrence.The combination of surgical resection and chemotherapy may be the best treatment.

Chidamide,Decitabine,Cytarabine,Aclarubicin,and Granulocyte Colony-stimulating Factor Therapy for Patients with Relapsed/Refractory Acute Myeloid Leukemia:A Retrospective Study from a Single-Center

Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.

Myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis with headache and kidney involvement at presentation and with arthralgia at relapse:A case report

BACKGROUND Patients with proteinase 3-antineutrophil cytoplasmic antibody associated vasculitis(AAV)experience different manifestations at the initial onset and relapse.However,such cases of different initial and relapse manifestations have not been reported in myeloperoxidase(MPO)-AAV patients.CASE SUMMARY A 52-year-old woman was admitted to our hospital because of headache.Laboratory findings indicated nephrotic range proteinuria and microscopic hematuria,serum creatinine of 243μmol/L,anti-MPO antibody titer of>400 RU/mL,and positive perinuclearantineutrophil cytoplasmic antibody.Renal biopsy showed pauci-immune crescentic glomerulonephritis.The cerebrospinal fluid examination and brain magnetic resonance imaging did not show any abnormality.Therefore,MPO-AAV was diagnosed.Corticosteroids,plasmapheresis,and cyclophosphamide as induction therapy and mycophenolate mofetil(MMF)as maintenance therapy were administered.The patient’s headache disappeared;serum creatinine returned to normal;complete remission of microscopic hematuria and proteinuria was observed.Anti-MPO antibody titer reached normal limits after immunosuppressive treatment.Twenty-five months after stopping the immunosuppressive treatment,the patient relapsed with arthralgia,without neurological or renal involvement.The patient’s arthralgia improved after treatment with prednisone and MMF.CONCLUSION We have reported a rare case of MPO-AAV who initially presented with headache and kidney involvement.However,relapse presented with only arthralgia,which was completely different from the initial manifestations.This case suggests that AAV relapse should be highly suspected in MPO-AAV patients after remission,when clinical manifestations at relapse are different from those at onset.Prednisone and MMF may provide a good choice for refractory arthralgia during relapse in MPO-AAV patients.

Dietary and metabolomic determinants of relapse in ulcerative colitis patients: A pilot prospective cohort study

AIM To identify demographic, clinical, metabolomic, and lifestyle related predictors of relapse in adult ulcerative colitis(UC) patients.METHODS In this prospective pilot study, UC patients in clinical remission were recruited and followed-up at 12 mo to assess a clinical relapse, or not. At baseline information on demographic and clinical parameters was collected. Serum and urine samples were collected for analysis of metabolomic assays using a combined direct infusion/liquid chromatography tandem mass spectrometry and nuclear magnetic resolution spectroscopy. Stool samples were also collected to measure fecal calprotectin(FCP). Dietary assessment was performed using a validated self-administered food frequency questionnaire. RESULTS Twenty patients were included(mean age: 42.7 ± 14.8 years, females: 55%). Seven patients(35%) experienced a clinical relapse during the follow-up period. While 6 patients(66.7%) with normal body weight developed a clinical relapse, 1 UC patient(9.1%) who was overweight/obese relapsed during the follow-up(P = 0.02). At baseline, poultry intake was significantly higher in patients who were still in remission during follow-up(0.9 oz vs 0.2 oz, P = 0.002). Five patients(71.4%) with FCP > 150 μg/g and 2 patients(15.4%) with normal FCP(≤ 150 μg/g) at baseline relapsed during the follow-up(P = 0.02). Interestingly, baseline urinary and serum metabolomic profiling of UC patients with or without clinical relapse within 12 mo showed a significant difference. The most important metabolites that were responsible for this discrimination were trans-aconitate, cystine and acetamide in urine, and 3-hydroxybutyrate, acetoacetate and acetone in serum. CONCLUSION A combination of baseline dietary intake, fecal calprotectin, and metabolomic factors are associated with risk of UC clinical relapse within 12 mo.

Normalization of ventral tegmental area structure following acupuncture in a rat model of heroin relapse

Drugs can cause obvious damage to the brain. To verify the relationship between acupuncture, neurotrophic factor expression and brain cell structural changes, this study established a rat model of heroin relapse using intramuscular injection of increasing amounts of heroin. During the detoxification period, rat models received acupuncture at Baihui （DU20） and Dazhui （DU14）. Electron microscopy demonstrated that the structure of the ventral tegmental area in heroin relapse rats gradually became normalized after acupuncture treatment. Immunohistochem- ical staining exhibited that the expression of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor increased in the ventral tegmental area following acupuncture. Moreover, the effects were similar to that of methadone, a type of medicine called an opioid. Results suggested that acupuncture at Baihui and Dazhui protected brain neurons against injury in rats with heroin relapse by promoting brain-derived neurotrophic factor and glial cell line-de-rived neurotrophic factor expression.

Decitabine for Relapsed Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine（DAC） for treating patients with acute lymphoblastic leukemia（ALL） who relapsed after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission（CR）, 1 achieved a partial remission（PR）, and 1 had no response（NR） after treatment at the latest follow-up（LFU）, the median survival was 11.2 months（range, 3.8–34, 7 months）. The 1-and 2-year overall survival（OS） rates were 50%（6/12） and 25%（3/12）, respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL（57.1% vs. 20%）. No aggravated flares of graft-versus-host disease（GVHD） were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.

New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma:a retrospective study

Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.Methods: A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat?sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R?CHOP regimen(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen(cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathe?cal chemotherapy prophylaxis(methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R?CHOP set in particular, the Kaplan–Meier method coupled with the log?rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Diferences were evaluated using a two?tailed test, and P < 0.05 was considered signiicant.Results: At a median follow?up of 46 months, 25(4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3?year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R?CHOP group(P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much beneit in terms of preventing CNS relapse. Bone involvement [hazard ratio(HR) = 4.21, 95% conidence interval(CI) 1.38–12.77], renal involvement(HR = 3.85, 95% CI 1.05–14.19), alkaline phosphatase(ALP) >110 U/L(HR = 3.59, 95% CI 1.25–10.34), serum albumin(ALB) <35 g/L(HR = 3.63, 95% CI 1.25–10.51), treatment with rituxi?mab(HR = 0.34, 95% CI 0.12–0.96), and a time to complete remission ≤ 108 days(HR = 0.22, 95% CI 0.06–0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement(HR = 4.44, 95% CI 1.08–18.35), bone marrow involvement(HR = 11.70, 95% CI 2.24–60.99), and renal involvement(HR = 10.83, 95% CI 2.27–51.65) were independent risk factors for CNS relapse in the R?CHOP set.Conclusions: In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemo?therapy prophylaxis alone was not suicient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R?CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.

Consecutive fecal calprotectin measurements for predicting relapse in pediatric Crohn's disease patients

BACKGROUND Asymptomatic children with Crohn's disease(CD) require ongoing monitoring to ensure early recognition of a disease exacerbation.AIM In a cohort of pediatric CD patients, we aimed to assess the utility of serial fecal calprotectin measurements to detect intestinal inflammatory activity and predict disease relapse.METHODS In this prospective longitudinal cohort study, children with CD on infliximab therapy in clinical remission were included. Fecal calprotectin levels were assessed at baseline and at subsequent 2-5 visits. Clinical and biochemical disease activity were assessed using the Pediatric Crohn's Disease Activity Index, Creactive protein and erythrocyte sedimentation rate at baseline and at visits over the following 18 mo.RESULTS 53 children were included and eighteen patients(34%) had a clinical disease relapse during the study. Baseline fecal calprotectin levels were higher in patients that developed symptomatic relapse [median(interquartile range), relapse 723μg/g(283-1758) vs 244 μg/g(61-627), P = 0.02]. Fecal calprotectin levels > 250μg/g demonstrated good predictive accuracy of a clinical flare within 3 mo(area under the receiver operator curve was 0.86, 95% confidence limits 0.781 to 0.937).CONCLUSION Routine fecal calprotectin testing in children with CD in clinical remission is useful to predict relapse. Levels > 250 μg/g are a good predictor of relapse in the following 3 mo. This information is important to guide monitoring standards used in this population.

Preferential loss of mismatch repair function in refractory and relapsed acute myeloid leukemia： potential contribution to AML proqression

Acute myeloid leukemia （AML） is an aggressive hematological cancer. Despite therapeutic regimens that lead to complete remission, the vast majority of patients undergo relapse. The molecular mechanisms underlying AML development and relapse remain incompletely defined. To explore whether loss of DNA mismatch repair （MMR） function is involved in AML, we screened two key MMR genes, MSH2 and MLH1, for mutations and promoter hypermethylation in leukemia specimens from 53 AML patients and blood from 17 non-cancer controls. We show here that whereas no amino acid alteration or promoter hypermethylation was detected in all control samples, 18 AML patients exhibited either mutations in MMR genes or hypermethylation in the MLH1 promoter. In vitro functional MMR analysis revealed that almost all the mutations analyzed resulted in loss of MMR function. MMR defects were significantly more frequent in patients with refractory or relapsed AML compared with newly diagnosed patients. These observations suggest for the first time that the loss of MMR function is associated with refractory and relapsed AML and may contribute to disease Datho8enesis.