Usefulness of the Hook knife in flexible endoscopic myotomy for Zenker's diverticulum

AIM To investigate the outcome of flexible endoscopic myotomy performed with the Hook knife in patients with symptomatic Zenker's diverticulum(ZD).METHODS All consecutive patients treated for ZD at our institution between 7/2012 and 12/2016 were included.The flexible endoscopic soft diverticuloscope-assisted technique with endoclips placement and Hook knife myotomy were performed in all patients.Here we report a retrospective review of prospectively collected data.Demographics,dysphagia score(Dakkak and Bennett),associated symptoms and adverse events were collected pre-procedure,at 2 and 6 mo post-procedure,and at the end of the follow-up period.Clinical success was defined as at least 1-point improvement in dysphagia score and a residual dysphagia score≤1,with no need for reintervention.Dysphagia scores were compared before treatment and at end-of-follow-up using the Wilcoxon test.RESULTS Twenty-four patients were included.Mean size of ZD was 3.0 cm(range 2-8 cm).Mean number of sessions was 1.17/patient(range 1-3 sessions).Overall clinical success was 91.7%.Two adverse events(8.3%) occurred,and both were managed conservatively.No bleeding or perforation was reported.Mild pain was reported by 9 patients(37.5%).Median hospital stay was 1 d(range 1-6).Median follow-up was 19.5 mo(range 6-53).Mean ± SD dysphagia score was 2.25±0.89 before treatment and decreased to 0.41 ± 0.92 at end-of-follow-up(P<0.001).Regurgitation and cough dropped from 91.7% and 50% to 12.5% and 0% at the end of follow-up,respectively.Recurrence was observed in 3 patients,and all 3 were symptom-free after one more session.CONCLUSION The Hook knife,used in the soft diverticuloscope-assisted technique setting,is efficient and safe for treatment of ZD.

Endoscopy-based management decreases the risk of postoperative recurrences in Crohn's disease

AIM: To investigate whether an endoscopy-based management could prevent the long-term risk of postoperative recurrence.METHODS: From the pathology department database, we retrospectively retrieved the data of all the patients operated on for Crohn's disease(CD) in our center(1986-2015). Endoscopy-based management was defined as systematic postoperative colonoscopy(median time after surgery = 9.5 mo) in patients with no clinical postoperative recurrence at the time of endoscopy. RESULTS: From 205 patients who underwent surgery, 161 patients(follow-up > 6 mo) were included. Endoscopic postoperative recurrence occurred in 67.6%, 79.7%, and 95.5% of the patients, respectively 5, 10 and 20 years after surgery. The rate of clinical postoperative recurrence was 61.4%, 75.9%, and 92.5% at 5, 10 and 20 years, respectively. The rate of surgical postoperative recurrence was 19.0%, 38.9% and 64.7%, respectively, 5, 10 and 20 years after surgery. In multivariate analysis, previous intestinal resection, prior exposure to anti-TNF therapy before surgery, and fistulizing phenotype(B3) were postoperative risk factors. Previous perianal abscess/fistula(other perianal lesions excluded), were predictive of only symptomatic recurrence. In multivariate analysis, an endoscopy-based management(n = 49/161) prevented clinical(HR = 0.4, 95%CI: 0.25-0.66, P < 0.001) and surgical postoperative recurrence(HR = 0.30, 95%CI: 0.13-0.70, P = 0.006).CONCLUSION: Endoscopy-based management should be recommended in all CD patients within the first year after surgery as it highly decreases the long-term risk of clinical recurrence and reoperation.

Combined evaluation of biomarkers as predictor of maintained remission in Crohn's disease

BACKGROUND The individual performances and the complementarity of Crohn's disease(CD)activity index(CDAI), C-reactive protein(CRP) and faecal calprotectin(Fcal) to monitor patients with CD remain poorly inves-tigated in the era of "tight control"and "treat to target" strategies.AIM To assess CDAI, CRP and Fcal variation, alone or combined, after 12 wk(W12) of anti-tumor necrosis factor(TNF) therapy to predict corticosteroids-free remission(CFREM = CDAI < 150, CRP < 2.9 mg/L and Fcal < 250 μg/g with no therapeutic intensification and no surgery) at W52.METHODS CD adult patients needing anti-TNF therapy with CDAI > 150 and either CRP >2.9 mg/L or Fcal > 250 μg/g were prospectively enrolled.RESULTS Among the 40 included patients, 13 patients(32.5%) achieved CFREM at W52. In univariable analysis, CDAI < 150 at W12(P = 0.012), CRP level < 2.9 mg/L at W12(P = 0.001) and Fcal improvement at W12(Fcal < 300 μg/g; or, for patients with initial Fcal < 300 μg/g, at least 50% decrease of Fcal or normalization of Fcal(< 100 μg/g)(P = 0.001) were predictive of CFREM at W52. Combined endpoint(CDAI < 150 and CRP ≤ 2.9 mg/L and FCal improvement) at W12 was the best predictor of CFREM at W52 with positive predictive value = 100.0%(100.0-100.0)and negative predictive value = 87.1%(75.3-98.9). In multivariable analysis, Fcal improvement at W12 [odd ratio(OR) = 45.1(2.96-687.9); P = 0.03] was a better predictor of CFREM at W52 than CDAI < 150 [OR = 9.3(0.36-237.1); P = 0.145]and CRP < 2.9 mg/L(0.77-278.0; P = 0.073).CONCLUSION The combined monitoring of CDAI, CRP and Fcal after anti-TNF induction therapy is able to predict favorable outcome within one year in patients with CD.

Construction of Parsimonious Event Risk Scores by an Ensemble Method. An Illustration for Short-Term Predictions in Chronic Heart Failure Patients from the GISSI-HF Trial

Selecting which explanatory variables to include in a given score is a common difficulty, as a balance must be found between statistical fit and practical application. This article presents a methodology for constructing parsimonious event risk scores combining a stepwise selection of variables with ensemble scores obtained by aggregation of several scores, using several classifiers, bootstrap samples and various modalities of random selection of variables. Selection methods based on a probabilistic model can be used to achieve a stepwise selection for a given classifier such as logistic regression, but not directly for an ensemble classifier constructed by aggregation of several classifiers. Three selection methods are proposed in this framework, two involving a backward selection of the variables based on their coefficients in an ensemble score and the third involving a forward selection of the variables maximizing the AUC. The stepwise selection allows constructing a succession of scores, with the practitioner able to choose which score best fits his needs. These three methods are compared in an application to construct parsimonious short-term event risk scores in chronic HF patients, using as event the composite endpoint of death or hospitalization for worsening HF within 180 days of a visit. Focusing on the fastest method, four scores are constructed, yielding out-of-bag AUCs ranging from 0.81 (26 variables) to 0.76 (2 variables).

Faecal calprotectin and magnetic resonance imaging in detecting Crohn's disease endoscopic postoperative recurrence

AIM To assess magnetic resonance imaging(MRI) and faecal calprotectin to detect endoscopic postoperative recurrence in patients with Crohn's disease(CD).METHODS From two tertiary centers, all patients with CD who underwent ileocolonic resection were consecutively and prospectively included. All the patients underwent MRI and endoscopy within the first year after surgery or after the restoration of intestinal continuity [median = 6 mo(5.0-9.3)]. The stools were collected the day before the colonoscopy to evaluate faecal calprotectin level. Endoscopic postoperative recurrence(POR) was defined as Rutgeerts' index ≥ i2b. The MRI was analyzed independently by two radiologists blinded from clinical data.RESULTS Apparent diffusion coefficient(ADC) was lower in patients with endoscopic POR compared to those with no recurrence(2.03 ± 0.32 vs 2.27 ± 0.38 × 10^(-3) mm^2/s, P = 0.032). Clermont score(10.4 ± 5.8 vs 7.4 ± 4.5, P = 0.038) and relative contrast enhancement(RCE)(129.4% ± 62.8% vs 76.4% ± 32.6%, P = 0.007) were significantly associated with endoscopic POR contrary to the magnetic resonance index of activity(Ma RIA)(7.3 ± 4.5 vs 4.8 ± 3.7; P = 0.15) and MR scoring system(P = 0.056). ADC < 2.35 × 10^(-3) mm^2/s [sensitivity = 0.85, specificity = 0.65, positive predictive value(PPV) = 0.85, negative predictive value(NPV) = 0.65] and RCE > 100%(sensitivity = 0.75, specificity = 0.81, PPV = 0.75, NPV = 0.81) were the best cutoff values to identify endoscopic POR. Clermont score > 6.4(sensitivity = 0.61, specificity = 0.82, PPV = 0.73, NPV = 0.74), Ma RIA > 3.76(sensitivity = 0.61, specificity = 0.82, PPV = 0.73, NPV = 0.74) and a MR scoring system ≥ MR1(sensitivity = 0.54, specificity = 0.82, PPV = 0.70, and NPV = 0.70) demonstrated interesting performances to detect endoscopic POR. Faecal calprotectin values were significantly higher in patients with endoscopic POR(114 ± 54.5 μg/g vs 354.8 ± 432.5 μg/g; P = 0.0075). Faecal calprotectin > 100 μg/g demonstrated high performances to detect endoscopic POR(sensitivity = 0.67, specificity = 0.93, PPV = 0.89 and NPV = 0.77).CONCLUSION Faecal calprotectin and MRI are two reliable tools to detect endoscopic POR in patients with CD.

WNT/β-catenin pathway and circadian rhythms in obsessive-compulsive disorder

The neuropsychiatric disease named obsessive-compulsive disorder is composed by obsessions and/or compulsions.Obsessive-compulsive disorder etiologies are undefined.However,numerous mechanisms in several localizations are implicated.Some studies showed that both glutamate,inflammatory factors and oxidative stress could have main functions in obsessive-compulsive disorder.Glycogen synthase kinase-3β,the major negative controller of the WNT/β-catenin pathway is upregulated in obsessive-compulsive disorder.In obsessive-compulsive disorder,some studies presented the actions of the different circadian clock genes.WNT/β-catenin pathway and circadian clock genes appear to be intricate.Thus,this review focuses on the interaction between circadian clock genes and the WNT/β-catenin pathway in obsessive-compulsive disorder.

Construction and Update of an Online Ensemble Score Involving Linear Discriminant Analysis and Logistic Regression

The present aim is to update, upon arrival of new learning data, the parameters of a score constructed with an ensemble method involving linear discriminant analysis and logistic regression in an online setting, without the need to store all of the previously obtained data. Poisson bootstrap and stochastic approximation processes were used with online standardized data to avoid numerical explosions, the convergence of which has been established theoretically. This empirical convergence of online ensemble scores to a reference “batch” score was studied on five different datasets from which data streams were simulated, comparing six different processes to construct the online scores. For each score, 50 replications using a total of 10N observations (N being the size of the dataset) were performed to assess the convergence and the stability of the method, computing the mean and standard deviation of a convergence criterion. A complementary study using 100N observations was also performed. All tested processes on all datasets converged after N iterations, except for one process on one dataset. The best processes were averaged processes using online standardized data and a piecewise constant step-size.

Opposite Interplay Between the Canonical WNT/β-Catenin Pathway and PPAR Gamma： A Potential Therapeutic Target in Gliomas

In gliomas, the canonical Wingless/Int（WNT）/b-catenin pathway is increased while peroxisome proliferator-activated receptor gamma（PPAR-c） is downregulated.The two systems act in an opposite manner. This review focuses on the interplay between WNT/b-catenin signaling and PPAR-c and their metabolic implications as potential therapeutic target in gliomas. Activation of the WNT/bcatenin pathway stimulates the transcription of genes involved in proliferation, invasion, nucleotide synthesis,tumor growth, and angiogenesis. Activation of PPAR-c agonists inhibits various signaling pathways such as the JAK/STAT, WNT/b-catenin, and PI3 K/Akt pathways,which reduces tumor growth, cell proliferation, cell invasiveness, and angiogenesis. Nonsteroidal anti-inflammatory drugs, curcumin, antipsychotic drugs, adiponectin,and sulforaphane downregulate the WNT/b-catenin pathway through the upregulation of PPAR-c and thus appear to provide an interesting therapeutic approach for gliomas.Temozolomide（TMZ） is an antiangiogenic agent. The downstream action of this opposite interplay may explain the TMZ-resistance often reported in gliomas.

Criteria deemed important by ICU patients when designating a reference person

Background:We investigated the criteria that hospitalized patients in intensive care units(ICUs)deem important when designating relatives who are best qualified to interact with the caregiving staff.Methods:We conducted an exploratory,observational,prospective,multicenter study between March 1,2018,and October 31,2018,within two ICUs.A 12-item questionnaire was distributed to patients in the ICUs by the investigating physicians.Patients were considered eligible if they had a good understanding of the French language and if they had not officially designated surrogates before ICU admission.Results:Seventy-one patients whose average age was 63.9±17.3 years,of whom 21(29.5%)were females,completed the questionnaire.The average Charlson comorbidity score was 2.5±2.4,and the average Simplified Acute Physiology Score(SAPS II)was 39.8±16.5.The main etiology was respiratory infection(40.8%),followed by sepsis(23.9%).The most important criteria identified by patients when selecting reference persons were a good knowledge of the patient’s wishes and values,an emotional attachment to the patient,and being a family member.Conclusion:Our findings reveal that ICU patients considered the following criteria to be critical when designating reference persons:knowledge of their wishes and the existence of emotional and family attachments.