Early Transmural Response Assessed Using Magnetic Resonance Imaging Could Predict Sustained Clinical Remission and Prevent Bowel Damage in Patients with Crohn's Disease Treated with Anti-Tumour Necrosis Factor Therapy.

BACKGROUND: Magnetic resonance imaging [MRI] is a promising tool to evaluate therapeutic efficacy in ileocolonic Crohn's disease [CD]. AIMS: We aimed to assess the feasibility of early MRI evaluation (week 12 [W12]) to predict corticosteroid-free remission [CFREM] at W52 and prevent long-term bowel damage. METHODS: All patients with active CD needing anti-tumour necrosis factor [anti-TNF] therapy were consecutively enrolled in this multicentre prospective study. MRI was performed before starting therapy, at W12 and W52. CFREM was defined as Crohn's Disease Activity Index < 150, C-reactive protein < 5 mg/L and faecal calprotectin < 250 µg/g, with no switch of anti-TNF agents, no bowel resection and no therapeutic intensification between W12 and W52. RESULTS: Among 46 patients, 22 [47.8%] achieved CFREM at W52. Anti-TNF agents were able to heal almost all CD lesions as soon as W12 [p < 0.05]. Early transmural response defined as a 25% decrease of either Clermont score (odds ratio [OR] = 7.7 [1.7-34.0], p < 0.001) or Magnetic Resonance Index of Activity (OR = 4.2 [1.3-13.3], p = 0.015) was predictive of CFREM at W52. Achieving at least two items on W12-MRI among ulceration healing, disappearance of enlarged lymph nodes or sclerolipomatosis, ΔADC [apparent diffusion coefficient] > +10% or ΔRCE [relative contrast enhancement] > -30% was associated with a likelihood of CFREM at W52 of 84.6% vs 37.5% in patients without transmural response [p < 0.001]. Early transmural response could prevent bowel damage progression over time using Clermont score (hazard ratio = 0.21 [0.0-0.9]; p = 0.037). CONCLUSION: Evaluation of early transmural response by MRI is feasible and is a promising end point to monitor therapeutic efficacy in patients with CD.

[Therapeutic strategies in patients undergoing surgery for non-small cell lung cancer. Results of the ESCAP-2011-CPHG study, promoted by the French College of General Hospital Respiratory Physicians (CPHG)]. / Stratégies thérapeutiques chez les patients opérés pour un carcinome bronchique non à petites cellules. Résultats de l'étude ESCAP-2011-CPHG réalisée par le Collège des pneumologues des hôpitaux généraux (CPHG).

BACKGROUND: The aim of ESCAP-2011-CPHG, promoted by the French College of General Hospital Respiratory Physicians, was to describe therapeutic strategies in lung cancer in the first 2 years after diagnosis, in a real-life setting. This article focuses on patients undergoing surgical management of a non-small cell lung cancer (NSCLC). METHODS: A prospective multicentre study was conducted in 53 French general hospitals. For each patient with lung cancer diagnosed in 2010, a standardised form was completed following each change in treatment strategy up to 2 years after diagnosis. RESULTS: Overall, 3418 of the 3943 included patients had NSCLC. 741 patients (21.7%) underwent curative surgery (stage 0-II, IIIA, IIIB, and IV: 65%, 27%, 3% and 5%, respectively). The therapeutic strategy changed less often in surgical than non-surgical patients and average follow-up time was longer: 23.3 months (SD: 9.3) versus 10.4 months (SD: 9.5) for non-surgical patients. Among patients with a surgical first strategy (92.6% of surgical patients as a whole), 56.9% did not receive any other treatment, 34.7% received chemotherapy, 5.9% radio-chemotherapy, 2.6% radiotherapy. At the end of follow-up, 55.8% were still alive without any other strategy, 13.1% had died, and 31.1% had received at least one more strategy. Among patients with a surgical second strategy, 63% had received chemotherapy alone during the first strategy. CONCLUSIONS: ESCAP -2011- CPHG assessed everyday professional practice in the surgical management of NSCLC in general hospitals. It pointed out the discrepancies between current guidelines and the therapeutic strategies applied in real life conditions.

Faecal chitinase 3-like 1 is a reliable marker as accurate as faecal calprotectin in detecting endoscopic activity in adult patients with inflammatory bowel diseases.

BACKGROUND: Faecal biomarkers are emerging tools in the assessment of mucosal healing in inflammatory bowel diseases (IBDs). AIM: To evaluate the accuracy of faecal chitinase 3-like 1(CHI3L1) compared to calprotectin in detecting endoscopic activity in IBD. METHODS: Overall, 86 IBD adults underwent colonoscopy consecutively and prospectively, with Crohn's disease Endoscopic Index of Severity (CDEIS) or Mayo endoscopic subscore calculation for ulcerative colitis, and stool collection. Faecal calprotectin was measured using quantitative immunochromatographic testing. Faecal CHI3L1 was quantified by ELISA. CHI3L1 cut-off value was determined using a receiver-operating curve. RESULTS: In 54 Crohn's disease patients, faecal CHI3L1 (ρ = 0.70, P < 0.001) and calprotectin (ρ = 0.74, P < 0.001) levels correlated with CDEIS and were significantly increased in patients with endoscopic ulceration. In patients with ileal Crohn's disease, faecal CHI3L1 seemed to be better correlated with CDEIS than faecal calprotectin (ρ = 0.78 vs. ρ = 0.62, P < 0.001 for both). CHI3L1 > 15 ng/g detected endoscopic ulceration in Crohn's disease with a sensitivity of 100% and a specificity of 63.6%, compared to faecal calprotectin > 250 µg/g showing a sensitivity of 90.5% and a specificity of 59.1%. In 32 ulcerative colitis patients, faecal CHI3L1 and calprotectin levels correlated with Mayo endoscopic subscore (ρ = 0.44 and 0.61, respectively, P < 0.001 for both) and were significantly increased in ulcerative colitis patients with endoscopic activity. In ulcerative colitis patients, faecal CHI3L1 > 15 ng/g predicted endoscopic activity with a sensitivity of 81.8% and a specificity of 80.0%, compared to faecal calprotectin>250 µg/g showing a sensitivity of 86.4% and a specificity of 80.0%. CONCLUSION: Faecal CHI3L1 is a reliable biomarker in detecting endoscopic activity in IBD.

Biliary stenting is not a prerequisite to endoscopic placement of duodenal covered self-expandable metal stents.

BACKGROUND: Duodenal covered self-expandable metal stent (cSEMS) can be used in malignant or benign gastroduodenal obstruction. The need for biliary stenting in patients with no concomitant biliary stricture, before duodenal cSEMS placement, remains unknown. The aim of this study was to determine whether cSEMS placement is responsible for biliary obstruction. METHODS: This is a single-center, retrospective, case-controlled study, including 106 patients with symptomatic gastric outlet obstruction or duodenal fistula who received a covered nitinol duodenal stent by using through-the-scope/over-the-wire placement procedure. The main outcome measurement was the occurrence comparison of jaundice and bilirubin level, between patients with previous or concomitant biliary stenting (cSEMS + BS group), and patients with no biliary stent (cSEMS group) during an observational period of 90 days. RESULTS: Hundred and six patients underwent cSEMS placement between June 2005 and March 2014: 53 in the cSEMS group (58% male, mean age 66.4 ± 13.3 years) and 53 in cSEMS + BS group (60% male, mean age 70.4 ± 11.6 years). The obstruction was due to cancer in 45% in cSEMS group and 87% in cSEMS + BS group. No case of jaundice was reported in the cSEMS group or in the cSEMS + BS group. In cSEMS group, the mean bilirubin level (µmol/L ± SD) was 8.0 ± 4 at baseline and 8.5 ± 4.6 at day 10, while in the cSEMS + BS group it was 91.4 ± 108 at baseline and 35.3 ± 39 at day 10 (p < 0.01). Patients from the two groups were matched on age, gender and bilirubin level at baseline. Evolution of bilirubinemia was +0.98 ± 2.76 µmol/L in experimental group and +0.39 ± 522 µmol/L in the control group (p = 0.34). No significant difference was observed between the two groups in term of technical success, clinical effectiveness, migration and other complications. CONCLUSIONS: Previous biliary stenting is not required before endoscopic covered duodenal stent placement in patients with no associated biliary obstruction. Prospective studies are needed.

Endoscopic Factors Influencing Fecal Calprotectin Value in Crohn's Disease.

BACKGROUND AND AIMS: Fecal calprotectin [fcal] is a biomarker of Crohn's disease [CD] endoscopic activity. Identifying the endoscopic situations in which fcal is less reliable remains unexplored. We aimed to determine the endoscopic factors influencing fcal level in CD. METHODS: Overall, 53 CD patients consecutively and prospectively underwent colonoscopy, with CD Endoscopic Index of Severity [CDEIS] calculation and stool collection. Fcal was measured using a quantitative immunochromatographic test. Correlation analysis was done with Pearson statistics. RESULTS: Fcal was correlated with CDEIS [0.66, p < 0.001]. In univariate analysis, fcal was correlated with the affected surface [0.65, p < 0.001] and the ulcerated surface [0.47, p < 0.001]. Fcal was significantly associated with ulceration depth, with median fcal of 867.5 µg/g, 1251.0 µg/g, and 1800.0 µg/g, in patients presenting with non-ulcerated lesions, superficial ulcerations [SU], and deep ulcerations [DU], respectively. Lesion locations did not influence fcal. In multivariate analysis, fcal was associated with affected surface [p = 0.04] and the presence of CD lesions. Moreover, fcal increased with the ulceration depth [p = 0.03]. However, ulcerated surface and CD location did not affect fcal. Using a receiver operating characteristic [ROC] curve, we showed that fcal of 400 µg/g was the best compromise between sensitivity [0.76] and specificity [0.77], whereas fcal ≥ 200 µg/g was highly sensitive [0.86] to detect SU or DU. CONCLUSIONS: Fcal is a very reliable biomarker to detect endoscopic ulcerations in CD. We suggest repeating measurement in case of intermediary results [200-400 µg/g] in daily practice. Fcal level is mostly influenced by the presence of CD lesions [even non-ulcerated], in a depth-related manner and by the affected surface.

Diffusion-weighted magnetic resonance imaging in ileocolonic Crohn's disease: validation of quantitative index of activity.

OBJECTIVES: Magnetic resonance imaging (MRI) allows accurate assessment of Crohn's disease (CD), but requires gadolinium injection. Diffusion-weighted (DW)-MRI yields comparable performances in small bowel CD. We compared the accuracy of DW-MR enterocolonography (MREC) and the magnetic resonance index of activity (MaRIA), and performed an external validation of the Clermont score in assessing inflammation in CD. METHODS: This was an observational prospective study of a single-center cohort. A total of 130 CD patients underwent consecutively MREC with gadolinium injection and DWI sequences between July 2011 and December 2012. RESULTS: Of the 848 evaluated segments (small bowel=352, colon/rectum=496), 175 (20.6%) were active (small bowel=111, colon/rectum=64) defined as MaRIA ≥7. Using a receiver operating characteristic (ROC) curve, we determined an apparent coefficient of diffusion (ADC) threshold of 1.9 × 10(-3) mm(2)/s that yielded a sensitivity and a specificity in discriminating active from nonactive CD of 96.9% and 98.1%, respectively, for the colon/rectum, and 85.9% and 81.6%, respectively, for the ileum. ADC was better correlated to MaRIA ≥7 than related contrast enhancement obtained with injected sequences (P<0.001). The Clermont score (=1.646 × bowel thickness-1.321 × ADC+5.613 × edema+8.306 × ulceration+5.039) was highly correlated with the MaRIA (rho=0.99) in ileal CD but not in colonic CD (rho <0.80). Interobserver agreement was high with regard to ADC measurement (correlation >0.9, P<0.001, and concordance >0.9, P<0001). CONCLUSIONS: DW-MREC is a reliable tool to assess inflammation in colonic (ADC) and ileal (Clermont score) CD and its use in daily practice would avoid gadolinium injection.

Generation and analysis of soybean plastid transformants expressing Bacillus thuringiensis Cry1Ab protoxin.

We describe the generation of fertile and homoplasmic soybean plastid transformants, expressing the Bacillus thuringiensis insecticidal protoxin Cry1Ab. Transgenes were targeted in the intergenic region of Glycine max plastome, between the rps12/7 and trnV genes and selection was carried out using the aadA gene encoding spectinomycin resistance. Molecular analysis confirmed the integration of the cry1Ab and aadA expression cassettes at the expected location in the soybean plastome, and the transmission of the transgenes to the next generation. Western blot analyses showed that the Cry1Ab protoxin is highly expressed in leaves, stems and seeds, but not in roots. Its expression confers strong insecticidal activity to the generated transgenic soybean, as exemplified with velvetbean caterpillar (Anticarsia gemmatalis).

The smaller helical repeat of poly(dA) . poly(dT) relative to DNA may reflect the wedge property of the dA . dT base pair.

A simple geometric approach is described which suggests that the smaller helical repeat of the homopolymer poly(dA) . poly(dT) relative to DNA (10.1 against 10.6 base pairs/turn) quantitatively reflects the property of the dA . dT base pair to behave like a wedge, of angle 11 degrees, pointing towards dA.