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Background Breast cancer is the most common malignancy observed in patients with inflammatory bowel diseases (IBD) unrelated to the disease or its treatment (Poullenot F et al. JCC 2022). The main aim of our study was to assess the risk of incident cancer according to the IBD treatment given in patients with prior breast cancer. Methods Consecutive IBD patients with prior breast cancer diagnosis were included in a multicenter retrospective cohort from 25 tertiary centres. Inclusion date corresponded to the diagnosis of index cancer. Follow up was calculated from the first administration of immunomodulator after cancer diagnosis (or cancer diagnosis date in absence of treatment) to the occurrence of incident cancer, corresponding to recurrence of breast cancer or de novo cancer, or to the last follow-up visit. Patients were categorized according to the use or not of immunomodulator after cancer diagnosis: thiopurines, methotrexate, anti-TNF, vedolizumab, ustekinumab. Crude incidence rates were compared between patients receiving at least one immunomodulator and those without immunomodulator before and after matching on age, lymph node, and metastasis extension and tumor’s grade, using a propensity-score analysis with a 1:1 ratio. Results Among the 151 identified patients, 80 patients with full available data were analyzed: 76 (95%) women; mean age at index cancer diagnosis: 51.5 years [standard deviation (SD): 11.5 years]; 44 (55%) with Crohn’s disease, 35 (44 %) ulcerative colitis and 1 (1 %) indeterminate colitis; median IBD duration at inclusion was 13 years [interquartile range (IQR) 6-21]. After a median follow up of 84 months [IQR 49-154], 16 (20%) incident cancers were observed: 12 (15%) recurrences and 4 (5%) cancer de novo. Three (4%) patients died from cancer related cause during the follow up. 39 (49%) patients received no immunomodulator and, 11 (14%) were treated with thiopurines, 6 (7.5%) with methotrexate, 18 (22.5%) with anti-TNF, 5 (6%) with vedolizumab and one (1%) with ustekinumab. Those treatments were initiated with a median interval of 24 months [IQR 7-48] after cancer diagnosis. Crude incidence rate per 1000 person-years were 47.97 for patients not exposed to any immunomodulator and 12.61 for the others (p=0.0248). After matching, adjusted crude incidence rates per 1000 person-years were 50 and 27.27, respectively (p=0.3798). Rates of survival without incident cancer were not different between the two groups after matching on age, lymph node, metastasis extension, and tumor’s grade (p=0.17) (Figure 1). Conclusion In the present multicenter retrospective cohort, incident cancer risk among patient with IBD and prior breast cancer was not increased in patients subsequently exposed to immunomodulators.

Introduction Knowledge about the cancer risk when initiating a biologic in inflammatory bowel disease [IBD] patients with prior malignancy remains scarce, especially for vedolizumab. Our aim was to evaluate the rate of incident cancer in a cohort of IBD patients with prior non-digestive malignancy, according to the subsequent treatment given. Methods A multicentre retrospective study included consecutive IBD patients with prior non-digestive malignancy. Inclusion date corresponded to the diagnosis of index malignancy. Patients were categorized into different cohorts according to the first treatment [none, conventional immunosuppressant, anti-TNF, or vedolizumab] to which they were exposed after inclusion and before incident cancer [recurrent or new cancer]. Results Among the 538 patients {58% female; mean (standard deviation [SD]) age inclusion: 52 [15] years} analyzed, the most frequent malignancy was breast cancer [25%]. The first immunomodulator given after inclusion was a conventional immunosuppressant in 27% of patients, anti-TNF in 21%, or vedolizumab in 9%. With a median (interquartile range [IQR]) follow-up duration of 55 [23-100] months, 100 incident cancers were observed. Crude cancer incidence rates per 1000 person-years were 47.0 for patients receiving no immunomodulator, 36.6 in the anti-TNF cohort, and 33.6 in the vedolizumab cohort [p = 0.23]. Incident-cancer free survival rates were not different between patients receiving anti-TNF and those receiving vedolizumab [p = 0.56]. After adjustment, incidence rates were not different between patients receiving no immunomodulator, anti-TNF, or vedolizumab. Conclusions In this large multicentre cohort study, there was no difference of cancer incidence in those IBD patients with prior non-digestive malignancy, treated with vedolizumab or anti-TNF.

Background Knowledge about the cancer risk when initiating a biologic in Inflammatory Bowel Disease (IBD) patients with prior malignancy remains scarce especially for vedolizumab. Our aim was to evaluate the rate of incident cancer in a cohort of IBD patients with prior non-digestive malignancy according to the subsequent treatment given. Methods Consecutive cases of patients with IBD and a malignancy were retrospectively collected in, 33 centers in two countries. Patients with a biliary- or digestive tract cancer were excluded. Inclusion date corresponded to diagnosis of malignancy. Patients were categorized into different cohorts according to the first treatment they were exposed to after the malignancy diagnosis and before incident cancer. Follow-up time was calculated from the first administration of therapy to last follow-up visit. For patients receiving no therapy, follow-up started at diagnosis of cancer. Incident cancer during follow-up was defined as recurrence of the known cancer or occurrence of a new cancer. Crude cancer incidence rates were compared between the cohorts using chi-square test. Patients from the anti-TNF, vedolizumab, and no treatment cohorts were matched on age, lymph node and metastasis extension and malignancy recurrence risk according to the Penn classification using a propensity-score analysis with a, 1:1 ratio. Results Among the, 538 patients (58% female; mean [standard deviation (SD)] age inclusion:, 52 [15] years) analyzed, the most frequent malignancy was breast cancer (25%). First immunomodulator given after inclusion was a conventional immunosuppressant in, 27% of patients, anti-TNF in, 21% or vedolizumab in, 9%. With a median (inter-quartile range (IQR)) follow-up duration of, 55 (23–100) months, 100 incident cancers were observed. Crude cancer incidence rates per, 1000 person-years were, 47.0 for patients receiving no immunomodulator, 36.6 in the anti-TNF cohort and, 33.6 in the vedolizumab cohort (p=0.23). Incident-cancer free survival rates were not different between patients receiving anti-TNF and those receiving vedolizumab (p=0.56). After adjustment, incidence rates were not different between patients receiving no immunomodulator, anti-TNF or vedolizumab. On multivariate analysis, age ≥, 52 years at inclusion, follow-up after index cancer Conclusion In this large multicenter cohort study, we found no difference in terms of incident cancer rates in patients with IBD and a prior non-digestive malignancy treated by vedolizumab compared to those treated by other immunomodulatory therapies including anti-TNF.

Background In the context of the Sars-Cov2 pandemic, the management of patients with chronic diseases and/or receiving immunosuppressive drugs was of concern due to lack of data to dictate their management. The objectives of our study were to evaluate the characteristics and prognosis of COVID-19 among IBD patients and to study the factors associated with severe COVID-19. Methods We carried out a multicentre bispective study in 30 French GETAID centres. Participating centres were asked to report all consecutive COVID19 cases occurring in their IBD-cohort between March,1st and December,31st 2020. The cases had to be confirmed by a PCR test, or by a chest CT scan demonstrating COVID19 lesions. In addition to the baseline examination, patients were scheduled for a follow up visit within 3–6 months following their infection. Demographics, disease characteristics, treatments, and the clinical course of IBD were prospectively recorded. Severe COVID-19 was defined as admission to the hospital >1 day and/or use of oxygen therapy and/or death. Predictive factors for developing severe COVID-19 were explored using univariate and multivariate logistic regression. Results A total of 719 IBD patients with COVID 19 were included; 54.2% were women, median age was 42 years, 64.4% had Crohn’s disease (CD), and median disease duration was 10.8 years. 13.3% of the patients were active smokers;12.7% had a BMI>30. With respect to the treatment, 72(10%) patients were not on any IBD medication, 75(10.4%) were only receiving 5-ASA, 164(22.8%) received conventional immunosuppressants, and 509(70.8%) biologics.21.6% of the patients developed either diarrhoea in remitters, or an exacerbation of diarrhoea in active patients. IBD treatments were maintained unchanged, suspended or discontinued in 73.4%, 25.5%, and 1.1% of the patients. Over the follow-up period, 13.2% of the patients had a flare. A total of 68 patients developed severe COVID 19, 67(9.3%) were hospitalized for a median duration of 6 days, and 4(0.6%) patients died. In multivariate analysis, age > 50 years (OR: 2.0,CI:1.06–3.72; p=0.031), obesity (OR: 2.01,CI:1.05–4.09; p=0.037), and comorbidities (OR: 3.28,CI:1.76–6.09; p=0.0002) were factors associated with the occurrence of severe COVID 19; while immunomodulatory treatment (biologic and/or immunosuppressant) was a protective factor for developing severe COVID 19 (OR: 0.38,CI: 0.22–0.69; p=0.0012). Conclusion Rate of severe COVID 19 in this cohort of IBD patients was corresponding to the general population with similar risk factors for severity, i.e., age, obesity and comorbidities. Prescription of immunomodulators was protective against severe COVID 19, raising the hypothesis of their potential immunological effect on the immune storm phase of Sars-Cov2.

D.J.-M. VIDON, S. DONZE, C. MULLER, A. ENTZMANN AND P. ANDRE. 2001. Aims:Listeria monocytogenes is capable, under certain conditions, of producing chemiluminescence which is amplified by luminol. This property was used to detect and count microcolonies of Listeria spp. in a few hours, without the use of a microscope. Methods and Results: After trapping Listeria cells on polyvinylidene fluoride membranes, a chemiluminescence mixture was sprayed onto the membrane. The chemiluminescent spots emitted were analysed by a charge-coupled device camera connected to a data-processing system, which restored the intensity of the signals into three dimensional images. The intensity of the luminescence of microcolonies was improved by addition of cellobiose, and by brief exposure to u.v. light. Conclusions: Microcolonies of Listeria spp. can be imaged and counted by luminol-enhanced chemiluminescence with a photon-counting system. Significance and Impact of the Study: This method can be applied to the rapid detection and counting of Listeria spp. in raw milk.

Almost all bacteria require iron for growth and virulence expression. However, Listeria spp. do not produce any siderophore for iron acquisition. Representative strains of each of the six species of Listeria were examined for their ability to use various compounds as iron suppliers in iron-restricted medium. Here we show that L. monocytogenes, L. innocua, L. ivanovii, L. welshimeri, L. seeligeri, and L. grayi were able to use exogenous siderophores and various catechol ligands, including catecholamines, to overcome growth inhibition induced by tropolone, an iron chelating agent. In contrast, no growth promoting effect was observed with normetanephrine or 4-hydroxy-3-methoxyphenylglycol-piperazine salt, which indicates that the o-diphenol function of the ligand must be free to allow iron acquisition. Furthermore, we demonstrate that catecholamines do not act through specific bacterial receptors, because no difference in growth stimulation was observed between [+]- and [-]-norepinephrine. These results show that utilization of a variety of catechol compounds to acquire iron is a general phenomenon in the genus Listeria.

Iron is an essential compound for the growth and virulence of Listeria monocytogenes. In extracellular environments, iron often requires a siderophore to be acquired by microorganisms. Although it does not produce siderophores, L. monocytogenes can use some exogenous bacterial or fungal siderophores as well as a number of animal or plant o-diphenol compounds to overcome growth inhibition by the iron-chelating agents tropolone and 8-hydroxyquinoline. Esculin, a plant glycoside, can be hydrolysed by L. monocytogenes to the o-diphenol aglucon, esculetin. The latter neutralized in vitro growth inhibition induced by the iron-chelating agents. Furthermore, when injected into infected mice, esculetin enhanced mortality in a dose-dependent manner and increased bacterial counts in spleen induced by sublethal doses of L. monocytogenes. Esculetin apparently functioned as a siderophore for L. monocytogenes in murine tissues.

Ninety samples of honey produced in eastern France, and 26 samples of honey originating from various countries, were analyzed for the presence of Clostridium botulinum spores. Although eight samples were found positive when using the mouse toxicity test, none of the strains isolated from the positive samples were identified as C. botulinum. This result is consistent with the hitherto rare occurrence of cases of infant botulism reported in France.

Listeria monocytogenes produces chemiluminescence in brain heart infusion broth at 37 degrees C in the presence of carbonate ions and acetaldehyde. This phenomenon can be enhanced by the use of luminol rather than acetaldehyde. Furthermore, there is direct relationship between the extent of growth and the level of luminescence which culminates at the end of the exponential growth. This property was used to study the susceptibility of this bacterium to two antiseptics, cetrimonium bromide and chlorhexidine, and to two antibiotics, ampicillin and chloramphenicol. Inhibition of chemiluminescence was proportional to the antimicrobial agents' concentrations and was complete at their minimal inhibitory concentrations.

All Enterococcus spp., isolated from environmental water samples (n = 81), emitted a high chemiluminescence signal in the presence of luminol (10 � 2 M). Kinetic studies of chemiluminescence show a close correlation between chemiluminescence and growth curves during the exponential phase, with a maximum chemiluminescence reached just before bacterial growth entered in the stationary phase. On the other hand, genera closely related to Enterococcus such as Streptococcus or Lactococcus produced a very weak chemiluminescent signal. Chemiluminescence of enterococci could therefore offer a rapid test, in aiding the identification of the genus Enterococcus and in the survey of the microbiological quality of water supplies. � 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

Listeria monocytogenes and Listeria innocua are able, under certain conditions, to produce chemiluminescence (CL), which is amplified by luminol. Kinetic studies of CL by L. monocytogenes and L. innocua show a close parallelism between CL and growth curves during the exponential phase, with a maximum of CL reached just before entrance of bacteria into the stationary phase. CL is tightly correlated with the release of oxygen compounds. The reactive oxygen species scavengers tryptophan, mannitol, and tiron, as well as cellobiose and high temperature, were assessed with regard to CL in the two Listeria species. Only tiron strongly reduced the CL emitted by L. monocytogenes and L. innocua. On the other hand, charcoal pretreatment of the growth medium inhibited the CL, whereas ferric citrate strongly increased the CL of L. monocytogenes and L. innocua. These data suggest that iron and superoxide radical are implicated in the CL produced by these bacteria, but this phenomenon is not correlated to virulence.

Listeria monocytogenes is a ubiquitous potentially pathogenic organism requiring iron for growth and virulence. Although it does not produce siderophores, L. monocytogenes is able to obtain iron by using either exogenous siderophores produced by various microorganisms or natural catechol compounds widespread in the environment. In the presence of tropolone, an iron-chelating agent, growth of L. monocytogenes is completely inhibited. However, the growth inhibition can be relieved by the addition of dopamine or norepinephrine under their different isomeric forms, while the catecholamine derivatives 4-hydroxy-3-methoxyphenylglycol and normetanephrine did not relieve the inhibitory effect of tropolone. Preincubation of L. monocytogenes with chlorpromazine and yohimbine did not antagonize the growth-promoting effect of catecholamines in iron-complexed medium. In addition, norepinephrine stimulated the growth-promoting effect induced by human transferrin in iron-limited medium. Furthermore, dopamine and norepinephrine allowed 55Fe uptake by iron-deprived bacterial cells. The uptake of iron was energy dependent, as indicated by inhibition of 55Fe uptake at 0 degrees C as well as by preincubating the bacteria with KCN. Inhibition of 55Fe uptake by L. monocytogenes was also observed in the presence of Pt(II). Moreover, when assessed by a whole-cell ferric reductase assay, reductase activity of L. monocytogenes was inhibited by Pt(II). These data demonstrate that dopamine and norepinephrine can function as siderophore-like compounds in L. monocytogenes owing to their ortho-diphenol function and that catecholamine-mediated iron acquisition does not involve specific catecholamine receptors but acts through a cell-bound ferrireductase activity.

Listeria monocytogenes does not produce siderophores for iron acquisition. We demonstrate that a number of microbial siderophores and natural iron-binding compounds are able to promote the growth of iron-starved L. monocytogenes. We suggest that the ability of L. monocytogenes to use a variety of exogenous siderophores and natural catechols accounts for its ubiquitous character.

A mercuric ion-reducing flavoprotein was purified from Yersinia enterocolitica 138A14 using dye matrix affinity chromatography. The purified enzyme had a characteristic absorption spectrum similar to those of flavin compounds, and FAD was detected as a part of the purified enzyme by thin-layer chromatography. Freshly purified preparations of the enzyme showed a single band on SDS polyacrylamide gel electrophoresis with a molecular weight of 70 000. The isolated enzyme had a molecular weight of about 200 000 as determined by gel filtration and disc gel electrophoresis. These results suggest an apparently trimeric structure of the enzyme. Dithiothreitol treatment disrupted the trimer into a dimeric structure of 140 000. Along with ageing, as well as limited proteolytic digestion, the enzyme evolved to give a dimeric molecule of 105 000 composed of two identical subunits of 52 000. The combination of the purified enzyme with HgCl2, or unexpectedly with merthiolate, oxidised the NADPH, which was followed spectrophotometrically. The Km for HgCl2 was dependent on the concentration of exogenous thiol compounds. A comparison of physical properties as well as kinetic characteristics indicated that the enzyme from Y. enterocolitica 138A14 is similar to mercuric reductases isolated from other mercury-resistant bacteria.Key words: Yersinia enterocolitica, mercury resistance, mercuric reductase.

Strains of Yersinia kristensenii display high susceptibility to carbenicillin (MIC90 less than 8 micrograms/ml) in comparison with the majority of environmental strains of Yersinia closely related to Y. enterocolitica which are resistant to this antibiotic (MIC90 greater than 256 micrograms/ml). beta-lactamases of 39 strains of Y. kristensenii isolated from foods were analysed by isoelectric focusing and gel electrophoresis of ultrasonically disrupted uninduced cultures. beta-lactamase patterns showed the presence of only one out of three classes of enzymes of pI 6.7, 7.6 and 8.2, respectively, by strain. One beta-lactamase showed electrophoretic mobility different (EM + 2.0 cm/h) from that of all the other enzymes (EM + 1.6 cm/h) belonging to the class of pI 7.6. Induction by cefoxitin revealed the existence of inducible beta-lactamases in two out of eight selected strains. The substrate profile of these enzymes, which are probably chromosomally mediated, showed a predominant cephalosporinase activity. None of the type A and B beta-lactamases described by Cornelis and Abraham in Y. enterocolitica were found in any of the strains examined. The lack of beta-lactamase A (a penicillinase) accounts for the carbenicillin susceptibility of Y. kristensenii strains.

A new transposon coding for mercury resistance (HgR), Tn3926, has been found in a strain of Yersinia enterocolitica, YE138A14. The element has a size of 7.8 kb and transposes to conjugative plasmids belonging to different incompatibility groups. A restriction map has been established. DNA-DNA hybridization indicates that Tn3926 displays homology with both Tn501 and Tn21; the greatest homology is shown with the regions of these transposons that encode HgR. Weaker homology is observed between Tn3926 sequences and those regions of Tn501 and Tn21 that encode transposition functions. Complementation experiments indicate that the Tn3926 transposase mediates transposition of Tn21, albeit somewhat inefficiently, but not of Tn501, while the resolvase mediates resolution of transposition cointegrates formed via Tn21, Tn501, or Tn1721.

A total of 75 raw milk samples collected from a central dairy or from retailers in Alsace, France, were analyzed for the presence of Yersinia enterocolitica. Three procedures were used: enrichment at 4 degrees C for 1 month; enrichment in modified Rappaport medium at room temperature for 72 h after a preenrichment at 4 degrees C for 1 month; and enrichment in a new medium containing sucrose, tris(hydroxymethyl)aminomethane, sodium azide, and ampicillin (PSTA) at 28 degrees C for 48 h after a preenrichment at 4 degrees C for 1 month. Isolation of Y. enterocolitica was made on Hektoen medium plus ampicillin. Sixty-one samples were positive (81.4%), but the PSTA medium produced the greatest number of isolates. Biochemical, serological, and phage typing of 40 isolates showed that chemotype 1 and serogroup O:5 were predominant. In seven cases, two different strains were obtained from the same samples. Most of the 66 isolates tested for their antimicrobial susceptibility were resistant to ampicillin and carbenicillin, and all were sensitive to tetracycline, chloramphenicol, streptomycin, sulfonamides, and mercuric ions.