Impact of Clinical and Pharmacological Parameters on Faecal Microbiota Transplantation Outcome in Clostridioides difficile Infections: Results of a 5-Year French National Survey.

Detailed comparative assessment of procedure-related factors associated with faecal microbiota transplantation (FMT) efficacy in Clostridioides difficile infection (CDI) is limited. We took advantage of the differences in procedures at the various French FMT centres to determine clinical and procedure-related factors associated with FMT success in CDI. We performed a nationwide retrospective multicentre cohort study. All FMTs performed within The French Faecal Transplant Group for CDI from 2018 to 2022 were included. Clinical data were collected retrospectively from recipient medical files, characteristics of stool transplant preparations were prospectively collected by each Pharmacy involved. Univariate and multivariate analyses were performed using Fisher's test and multiple logistic regression. Six hundred fifty-eight FMTs were performed for 617 patients in 17 centres. The overall efficacy of FMT was 84.3% (520/617), with 0.5% of severe adverse events possibly related to FMT (3/658). Forty-seven patients were treated at the first recurrence of CDI with a similar success rate (85.1%). Severe chronic kidney disease (CKD; OR: 2.18, 95%CI [1.20-3.88]), non-severe refractory CDI (OR: 15.35, [1.94-318.2]), the use of ≥ 80% glycerol (OR: 2.52, [1.11-5.67]), insufficient bowel cleansing (OR: 5.47, [1.57-20.03]) and partial FMT retention (OR: 9.97, [2.62-48.49]) were associated with CDI recurrence within 8 weeks. Conditions of transplant manufacturing, bowel cleansing, and a route of delivery tailored to the patient's characteristics are key factors in optimising FMT efficacy. FMT at first recurrence showed high success in real-life practice, whereas it had lower efficacy in severe CDI and non-severe refractory CDI

French national cohort of first use of dalbavancin: a high proportion of off-label use

Dalbavancin is a glycopeptide antibiotic with a long half-life, recently marketed in Europe for skin and soft tissue infections (SSTI), but real-life use is not well-known. We aimed to describe all first prescriptions in France over an 18-month period. We performed a retrospective study on all adult patients who received at least one dose of dalbavancin from July 1, 2017 to September 31, 2018. Data were collected thanks to a standard questionnaire. Failure was defined as: persistent or reappearance of signs of infection; and/or switch to suppressive antibiotic treatment; and/or death from infection. We included 75 patients from 29 French hospitals. Main indications were bone and joint infections (BJIs) (64.0%), endocarditis (25.3%), and SSTIs (17.3%). Main bacteria involved were: Staphylococcus aureus (51.4%), including methicillin-resistant S. aureus (MRSA) (19.4%); and coagulase-negative staphylococci (CNS) (44.4%). Median MICs for staphylococci to vancomycin and dalbavancin ranged from 0.875 mg/L to 2.0 mg/L, and 0.040 mg/L to 0.064 mg/L, respectively. Dalbavancin was used after a mean of 2.3 ± 1.2 lines of antimicrobial treatment. Main treatment regimens for dalbavancin were a weekly 2-dose regimen (1500mg each) in 38 (53.2%) cases, and a single-dose regimen (1500mg) in 13 (18.3%) cases. Overall, at the patients\u27 last visit, clinical cure was observed in 54/72 patients, while failure was found in 14/72 patients. First uses of dalbavancin in France were mostly off-label. Most of them were due to BJIs, and often as rescue therapy for severe infections. Even in off-label situations, dalbavancin seems safe and effective

Serum Early Prostate Cancer Antigen (EPCA) Level and Its Association with Disease Progression in Prostate Cancer in a Chinese Population

BACKGROUND: Early prostate cancer antigen (EPCA) has been shown a prostate cancer (PCa)-associated nuclear matrix protein, however, its serum status and prognostic power in PCa are unknown. The goals of this study are to measure serum EPCA levels in a cohort of patients with PCa prior to the treatment, and to evaluate the clinical value of serum EPCA. METHODS: Pretreatment serum EPCA levels were determined with an ELISA in 77 patients with clinically localized PCa who underwent radical prostatectomy and 51 patients with locally advanced or metastatic disease who received primary androgen deprivation therapy, and were correlated with clinicopathological variables and disease progression. Serum EPCA levels were also examined in 40 healthy controls. RESULTS: Pretreatment mean serum EPCA levels were significantly higher in PCa patients than in controls (16.84 ± 7.60 ng/ml vs. 4.12 ± 2.05 ng/ml, P<0.001). Patients with locally advanced and metastatic PCa had significantly higher serum EPCA level than those with clinically localized PCa (22.93 ± 5.28 ng/ml and 29.41 ± 8.47 ng/ml vs. 15.17 ± 6.03 ng/ml, P = 0.014 and P<0.001, respectively). Significantly elevated EPCA level was also found in metastatic PCa compared with locally advanced disease (P < 0.001). Increased serum EPCA levels were significantly and positively correlated with Gleason score and clinical stage, but not with PSA levels and age. On multivariate analysis, pretreatment serum EPCA level held the most significantly predictive value for the biochemical recurrence and androgen-independent progression among pretreatment variables (HR = 4.860, P<0.001 and HR = 5.418, P<0.001, respectively). CONCLUSIONS: Serum EPCA level is markedly elevated in PCa. Pretreatment serum EPCA level correlates significantly with the poor prognosis, showing prediction potential for PCa progression

Bacterial diversity and specific taxa are associated with decolonization of carbapenemase-producing enterobacterales after fecal microbiota transplantation

Objectives: We evaluated the effect of fecal microbiota transplantation (FMT) on the clearance of carbapenemase-producing Enterobacterales (CPE) carriage. Methods: We performed a prospective, multi-center study, conducted among patients who received a single dose of FMT from one of four healthy donors. The primary endpoint was complete clearance of CPE carriage two weeks after FMT with a secondary endpoint at three months. Shotgun metagenomic sequencing was performed to assess gut microbiota composition of donors and recipients before and after FMT. Results: Twenty CPE-colonized patients were included in the study, where post-FMT 20% (n = 4/20) of patients met the primary endpoint and 40% (n = 8/20) of patients met the secondary endpoint. KaplanMeier curves between patients with FMT intervention and the control group (n = 82) revealed a similar rate of decolonization between groups. Microbiota composition analyses revealed that response to FMT was not donor-dependent. Responders had a significantly lower relative abundance of CPE species pre-FMT than non-responders, and 14 days postFMT responders had significantly higher bacterial species richness and alpha diversity compared to nonresponders (p Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc

IGFBP-rP1, a potential molecule associated with colon cancer differentiation

<p>Abstract</p> <p>Background</p> <p>In our previous studies, we have demonstrated that insulin-like growth factor binding protein-related protein1 (IGFBP-rP1) played its potential tumor suppressor role in colon cancer cells through apoptosis and senescence induction. In this study, we will further uncover the role of IGFBP-rP1 in colon cancer differentiation and a possible mechanism by revealing responsible genes.</p> <p>Results</p> <p>In normal colon epithelium, immunohistochemistry staining detected a gradient IGFBP-rP1 expression along the axis of the crypt. IGFBP-rP1 strongly expressed in the differentiated cells at the surface of the colon epithelium, while weakly expressed at the crypt base. In colon cancer tissues, the expression of IGFBP-rP1 correlated positively with the differentiation status. IGFBP-rP1 strongly expressed in low grade colorectal carcinoma and weakly expressed in high grade colorectal carcinoma. In vitro, transfection of PcDNA3.1(IGFBP-rP1) into RKO, SW620 and CW2 cells induced a more pronounced anterior-posterior polarity morphology, accompanied by upregulation with alkaline phosphatase (AKP) activity. Upregulation of carcino-embryonic antigen (CEA) was also observed in SW620 and CW2 transfectants. The addition of IGFBP-rP1 protein into the medium could mimic most but not all effects of IGFBP-rP1 cDNA transfection. Seventy-eight reproducibly differentially expressed genes were detected in PcDNA3.1(IGFBP-rP1)-RKO transfectants, using Affymetrix 133 plus 2.0 expression chip platform. Directed Acyclic Graph (DAG) of the enriched GO categories demonstrated that differential expression of the enzyme regulator activity genes together with cytoskeleton and actin binding genes were significant. IGFBP-rP1 could upreguate Transgelin (TAGLN), downregulate SRY (sex determining region Y)-box 9(campomelic dysplasia, autosomal sex-reversal) (SOX9), insulin receptor substrate 1(IRS1), cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) (CDKN2B), amphiregulin(schwannoma-derived growth factor) (AREG) and immediate early response 5-like(IER5L) in RKO, SW620 and CW2 colon cancer cells, verified by Real time Reverse Transcription Polymerase Chain Reaction (rtRT-PCR). During sodium butyrate-induced Caco2 cell differentiation, IGFBP-rP1 was upregulated and the expression showed significant correlation with the AKP activity. The downregulation of IRS1 and SOX9 were also induced by sodium butyrate.</p> <p>Conclusion</p> <p>IGFBP-rP1 was a potential key molecule associated with colon cancer differentiation. Downregulation of IRS1 and SOX9 may the possible key downstream genes involved in the process.</p

Covid-19 : mise à jour des stratégies thérapeutiques curatives précoces et du patient sous oxygénothérapie

International audienceIntroduction. — Il existe désormais dans la prise en charge du COVID-19 des traitements préventifs mais également curatifs à la phase précoce et avancée de la maladie.État des connaissances. — Les antibiotiques n’ont pas leur place dans la prise en charge thérapeutique initiale d’une pneumonie à Sars-Cov-2. En revanche, chez les patients nécessitantune oxygénothérapie ≥ 2 L/min, les corticostéroïdes sont recommandés. Selon les dernièresrecommandations, le nirmatrelvir/ritonavir est indiqué en traitement précoce chez les adultesne nécessitant pas d’oxygénothérapie à risque élevé d’évolution vers une forme grave de laCOVID-19. En cas de contre-indication, le remdesivir constitue une alternative thérapeutique.Perspectives. — Bien qu’il n’y ait pas d’indication du plasma de convalescents en dehors d’essaiscliniques, ce dernier semble intéressant chez les patients immunodéprimés notamment ayantune lymphopénie B. À noter que dans la période actuelle avec une prédominance du variant Omicron XBB.1.5, les anticorps monoclonaux n’ont plus leur place en thérapeutique à l’exceptionfait du sotrovimab après avis d’expert, en sauvetage, au sein d’une stratégie bien définie aupréalable.Conclusion. — Malgré l’évolution des variants, les antiviraux semblent garder une activité etrestent le traitement de première intention des patients, en complément de la vaccination