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INTRODUCTION: Fecal microbiota transfer (FMT) is a treatment to modulate the gastrointestinal microbiota. Its use in recurrent Clostridioides difficile infection (rCDI) is established throughout Europe and recommended in national and international guidelines. In Germany, the FMT is codeable in the hospital reimbursement system. A comprehensive survey on the frequency of use based on this coding is missing so far. MATERIAL AND METHODOLOGY: Reports of the Institute for Hospital Remuneration (InEK), the Federal Statistical Office (DESTATIS), and hospital quality reports 2015-2021 were examined for FMT coding and evaluated in a structured expert consultation. RESULTS: Between 2015 and 2021, 1,645 FMT procedures were coded by 175 hospitals. From 2016 to 2018, this was a median of 293 (274-313) FMT annually, followed by a steady decline in subsequent years to 119 FMT in 2021. Patients with FMT were 57.7% female, median age 74 years, and FMT was applied colonoscopically in 72.2%. CDI was the primary diagnosis in 86.8% of cases, followed by ulcerative colitis in 7.6%. DISCUSSION: In Germany, FMT is used less frequently than in the European comparison. One application hurdle is the regulatory classification of FMT as a non-approved drug, which leads to significantly higher costs in manufacturing and administration and makes reimbursement difficult. The European Commission recently proposed a regulation to classify FMT as a transplant. This could prospectively change the regulatory situation of FMT in Germany and thus contribute to a nationwide offer of a therapeutic procedure recommended in guidelines.
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Clostridioides difficile , Infecciones por Clostridium , Microbioma Gastrointestinal , Humanos , Femenino , Anciano , Masculino , Trasplante de Microbiota Fecal/métodos , Infecciones por Clostridium/terapia , Alemania/epidemiología , Resultado del Tratamiento , RecurrenciaRESUMEN
BACKGROUND: Adenoma detection with polypectomy during total colonoscopy reduces the incidence of colorectal cancer (CRC) and colorectal cancer-associated mortality. The adenoma detection rate (ADR) is an established quality indicator, which is associated with a decreased risk for interval cancer. An increase in ADR could be demonstrated for several artificially intelligent, real-time computer-aided detection (CADe) systems in selected patients. Most studies concentrated on outpatient colonoscopies. This sector often lacks funds for applying costly innovations like CADe. Hospitals are more likely to implement CADe and information about the impact of CADe in the distinct patient cohort of hospitalized patients is scarce. METHODS: In this prospective, randomized-controlled study, we compared colonoscopies performed with or without computer-aided detection (CADe) system (GI Genius, Medtronic) performed at University Medical Center Schleswig-Holstein, Campus Luebeck. The primary endpoint was ADR. RESULTS: Overall, 232 patients were randomized with n = 122 patients in the CADe arm and n = 110 patients in the control arm. Median age was 66 years (interquartile range 51-77). Indication for colonoscopy was most often workup for gastrointestinal symptoms (88.4%) followed by screening, post-polypectomy and post-CRC surveillance (each 3.9%). Withdrawal time was significantly prolonged (11 vs. 10 min, p = 0.039), without clinical relevance. Complication rate was not different between the arms (0.8% vs. 4.5%; p = 0.072). The ADR was significantly increased in the CADe arm compared to the control (33.6% vs. 18.1%, p = 0.008). ADR increase was particularly strong for the detection in elderly patients aged ≥50 years (OR 6.3, 95% CI 1.7 - 23.1, p = 0.006). CONCLUSION: The use of CADe is safe and increases ADR in hospitalized patients.
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Adenoma , Pólipos del Colon , Neoplasias Colorrectales , Anciano , Humanos , Estudios Prospectivos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Colonoscopía , Computadores , Adenoma/diagnóstico , Adenoma/epidemiología , Pólipos del Colon/diagnósticoRESUMEN
Esophagogastroduodenoscopy (EGD), endoscopic retrograde cholangiopancreatography (ERCP) and colonoscopy (CLN) come with a potential risk of pathogen transmission. Unfortunately, up to now data on the causes and the distribution of pathogens is rather sparse.We performed a systematic review of the medical literature using the Worldwide Outbreak Database, the PubMed, and Embase. We then checked so-retrieved articles for potential sources of the outbreak, the spectrum of pathogens, the attack rates, mortality and infection control measures.In total 73 outbreaks (EGD: 24, ERCP: 42; CLN: 7) got included. The corresponding attack rates were 3.5%, 7.1% and 12.8% and mortality rates were 6.3%, 12.7% and 10.0% respectively. EGD was highly associated with transmission of enterobacteria including a large proportion of multi-drug resistant strains. ERCP led primarily to transmission of non-fermenting gram-negative rods. The most frequent cause was human failure during reprocessing regardless of the type of endoscope.Staff working in the field of endoscopy should always be aware of the possibility of pathogen transmission in order to detect and terminate those events at the early most time point. Furthermore, proper ongoing education of staff involved in the reprocessing and maintenance of endoscopes is crucial. Single-use devices may be an alternative option and lower the risk of pathogen transmission, but on the downside may also increase costs and waste.
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Infección Hospitalaria , Humanos , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Endoscopía Gastrointestinal , Endoscopios/microbiología , Colangiopancreatografia Retrógrada Endoscópica , Brotes de Enfermedades/prevención & controlRESUMEN
This study aims to characterize the biliary microbiome as neglected factor in patients with ischaemic-type biliary lesions (ITBL) after liver transplantation. Therefore, the V1-V2 region of the 16S rRNA gene was sequenced in 175 bile samples. Samples from patients with anastomotic strictures (AS) served as controls. Multivariate analysis and in silico metagenomics were applied cross-sectionally and longitudinally. The microbial community differed significantly between ITBL and AS in terms of alpha and beta diversity. Both, antibiotic treatment and stenting were associated independently with differences in the microbial community structure. In contrast to AS, in ITBL stenting was associated with pronounced differences in the biliary microbiome, whereas no differences associated with antibiotic treatment could be observed in ITBL contrasting the pronounced differences found in AS. Bacterial pathways involved in the production of antibacterial metabolites were increased in ITBL with antibiotic treatment. After liver transplantation, the biliary tract harbours a complex microbial community with significant differences between ITBL and AS. Fundamental changes in the microbial community in ITBL can be achieved with biliary stenting. However, the effect of antibiotic treatment in ITBL was minimal. Therefore, antibiotics should be administered wisely in order to reduce emerging resistance of the biliary microbiome towards external antibiotics.
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Sistema Biliar , Microbiota , Antibacterianos/uso terapéutico , Humanos , Isquemia , ARN Ribosómico 16SRESUMEN
BACKGROUND: Asymptomatic C. difficile colonization is believed to predispose to subsequent C. difficile infection (CDI). While emerging insights into the role of the commensal microbiota in mediating colonization resistance against C. difficile have associated CDI with specific microbial components, corresponding prospectively collected data on colonization with C. difficile are largely unavailable. METHODS: C. difficile status was assessed by GDH EIA and real-time PCR targeting the toxin A (tcdA) and B (tcdB) genes. 16S V3 and V4 gene sequencing results from fecal samples of patients tested positive for C. difficile were analyzed by assessing alpha and beta diversity, LefSe, and the Piphillin functional inference approach to estimate functional capacity. RESULTS: 1506 patients were recruited into a prospective observational study (DRKS00005335) upon admission into one of five academic hospitals. 936 of them provided fecal samples on admission and at discharge and were thus available for longitudinal analysis. Upon hospital admission, 5.5% (83/1506) and 3.7% (56/1506) of patients were colonized with toxigenic (TCD) and non-toxigenic C. difficile (NTCD), respectively. During hospitalization, 1.7% (16/936) acquired TCD. Risk factors for acquisition of TCD included pre-existing lung diseases, lower GI endoscopy and antibiotics. Species protecting against hospital-related C. difficile acquisition included Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii and other Ruminococcus spp. Metagenomic pathway analysis identified steroid biosynthesis as the most underrepresented metabolic pathway in patients who later acquire C. difficile colonization. CONCLUSIONS: Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii and other Ruminococci were associated with a decreased risk of C. difficile acquisition. CLINICAL TRIALS REGISTRATION: DRKS00005335.
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Toxinas Bacterianas , Clostridioides difficile , Infecciones por Clostridium , Microbiota , Toxinas Bacterianas/genética , Bacteroidetes , Clostridioides , Clostridioides difficile/genética , Infecciones por Clostridium/epidemiología , Heces , Humanos , Estudios Prospectivos , Factores de Riesgo , RuminococcusAsunto(s)
Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Ictericia , Linfoma de Células B Grandes Difuso , Humanos , Adulto , Trasplante Autólogo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/patología , Protocolos de Quimioterapia Combinada Antineoplásica , Aumento de Peso , Enfermedad Veno-Oclusiva Hepática/tratamiento farmacológico , Enfermedad Veno-Oclusiva Hepática/patologíaRESUMEN
BACKGROUND: Reports of head and neck ultrasound examinations are frequently written by hand as free texts. Naturally, quality and structure of free text reports is variable, depending on the examiner's individual level of experience. Aim of the present study was to compare the quality of free text reports (FTR) and structured reports (SR) of head and neck ultrasound examinations. METHODS: Both standard FTRs and SRs of head and neck ultrasound examinations of 43 patients were acquired by nine independent examiners with comparable levels of experience. A template for structured reporting of head and neck ultrasound examinations was created using a web-based approach. FTRs and SRs were evaluated with regard to overall quality, completeness, required time to completion, and readability by four independent raters with different specializations (Paired Wilcoxon test, 95% CI) and inter-rater reliability was assessed (Fleiss' kappa). A questionnaire was used to compare FTRs vs. SRs with respect to user satisfaction (Mann-Whitney U test, 95% CI). RESULTS: By comparison, completeness scores of SRs were significantly higher than FTRs' completeness scores (94.4% vs. 45.6%, p < 0.001), and pathologies were described in more detail (91.1% vs. 54.5%, p < 0.001). Readability was significantly higher in all SRs when compared to FTRs (100% vs. 47.1%, p < 0.001). The mean time to complete a report, however, was significantly higher in SRs (176.5 vs. 107.3 s, p < 0.001). SRs achieved significantly higher user satisfaction ratings (VAS 8.87 vs. 1.41, p < 0.001) and a very high inter-rater reliability (Fleiss' kappa 0.92). CONCLUSIONS: As compared to FTRs, SRs of head and neck ultrasound examinations are more comprehensive and easier to understand. On the balance, the additional time needed for completing a SR is negligible. Also, SRs yield high inter-rater reliability and may be used for high-quality scientific data analyses.
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Cabeza/diagnóstico por imagen , Cuello/diagnóstico por imagen , Proyectos de Investigación/normas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Registros Médicos/normas , Persona de Mediana Edad , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND & AIMS: Ribavirin (RBV) is commonly used for the treatment of hepatitis C virus (HCV) infection. However, RBV is associated with a reduced quality of life (QOL). We aim to assess the impact of RBV on QOL in a real-world setting. METHODS: In a prospective study, QOL was measured by a SF-36 questionnaire in 174 patients. In all, 85 patients were treated with RBV and 89 patients without RBV. QOL was assessed at baseline, week 12 of treatment and 24 weeks after treatment. RESULTS: Patients treated with RBV were more likely to have HCV genotype 2 and 3 infection and cirrhosis (all P < .05). RBV-treated patients reported lower scores for several domains of QOL already at baseline. During HCV treatment, RBV-free treatment led to an increase in all measured dimensions of quality of life, whereas RBV treatment led to a decrease in the emotional and physical functioning. After treatment, all dimensions for QOL showed improvement across the study cohort, regardless whether RBV was part of the treatment regimen. However, 28.8%-45.2% of treated patients perceive a sustained reduction in their physical or mental capacity after treatment, not related to RBV usage or SVR, but related to older age (P = .03) and cirrhosis (P = .02). CONCLUSIONS: During treatment, RBV leads to a reduced QOL, whereas RBV-free treatment leads to an increased QOL. After treatment, QOL strongly increases in both, RBV and RBV-free treated patients. Some patients perceive a sustained reduction in QOL, which seems unrelated to treatment.
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Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Ribavirina/uso terapéutico , Anciano , Femenino , Hepacivirus , Hepatitis C/complicaciones , Humanos , Interferón-alfa , Cirrosis Hepática/virología , Masculino , Salud Mental , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: The importance of the intestinal microbiota for the onset and clinical course of many diseases, including liver diseases like non-alcoholic steatohepatitis and cirrhosis, is increasingly recognized. However, the role of intestinal microbiota in chronic hepatitis C virus (HCV) infection remains unclear. METHODS: In a cross-sectional approach, the intestinal microbiota of 95 patients chronically infected with HCV (n=57 without cirrhosis [NO-CIR]; n=38 with cirrhosis [CIR]) and 50 healthy controls (HC) without documented liver diseases was analysed. RESULTS: Alpha diversity, measured by number of phylotypes (S) and Shannon diversity index (H'), decreased significantly from HC to NO-CIR to CIR. S and H' correlated negatively with liver elastography. Analysis of similarities revealed highly statistically significant differences in the microbial communities between HC, NO-CIR and CIR (R=.090; P<1.0×10-6 ). Stratifying for HCV genotypes even increased the differences. In addition, we observed distinct patterns in the relative abundance of genera being either positive or negative correlated with diseases status. CONCLUSIONS: This study shows that not only the stage of liver disease but also HCV infection is associated with a reduced alpha diversity and different microbial community patterns. These differences might be caused by direct interactions between HCV and the microbiota or indirect interactions facilitated by the immune system.
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Bacterias/clasificación , Microbioma Gastrointestinal , Tracto Gastrointestinal/microbiología , Hepacivirus/patogenicidad , Hepatitis C Crónica/microbiología , Cirrosis Hepática/microbiología , Adulto , Anciano , Estudios de Casos y Controles , Estudios Transversales , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/virología , Interacciones Huésped-Patógeno , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Adulto JovenAsunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: Currently only vague estimates exist for the seroprevalence and vaccination status for viral hepatitis B (HBV) in refugees arriving in Germany during the current refugee crisis. OBJECTIVES: To assess the prevalence of hepatitis B in refugees arriving in northern Germany in 2015. METHODS: In a cross-sectional study in 793 patients from all age groups tests for serological markers of hepatitis B virus infection (HBsAg, anti-HBc) and liver enzymes (ALT, AST, bilirubin, γGT, alkaline phosphatase) were performed in August 2015 at six reception centers in northern Germany. In 258 patients anti-HBs antibodies were assessed additionally. RESULTS: Of the tested refugees, 76.7 % were male, the median age was 28.8 ± 11.4 years, and 7.8 % were children under the age of 18. The overall prevalence of HBsAg and total anti-HBc was 2.3 % and 14.0 % respectively (2.5 % and 14.5 % in men; 1.2 % and 13.5 % in women). Prevalence was highest in 35 to 49-year-old patients for HBsAg (3.1 %) and for refugees over 50 years for anti-HBc (38 %). No immunity to Hepatitis B was found in 62 %, 18.6 % had been vaccinated against Hepatitis B, while 50 % of children aged up to 15 years (n = 12) had been vaccinated. Positive predictive values of elevated AST and ALT for detection of HBsAg was 0 and 0.016, respectively. Only two patients with a positive HBsAg had elevated transaminases. CONCLUSIONS: This study showed a high prevalence of HBsAg in a German refugee sample in comparison to the general German population. Liver enzymes are not an appropriate tool for screening for hepatitis B virus infection.
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Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Refugiados/estadística & datos numéricos , Transaminasas/sangre , Vacunación/estadística & datos numéricos , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Niño , Preescolar , Pruebas Enzimáticas Clínicas/estadística & datos numéricos , Femenino , Alemania/epidemiología , Hepatitis B/prevención & control , Vacunas contra Hepatitis B/uso terapéutico , Humanos , Lactante , Recién Nacido , Pruebas de Función Hepática/métodos , Pruebas de Función Hepática/estadística & datos numéricos , Masculino , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Prevalencia , Pronóstico , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y Especificidad , Estudios Seroepidemiológicos , Distribución por Sexo , Adulto JovenRESUMEN
BACKGROUND: Continuous use of anabolic androgenic steroid in high-doses is associated with substantial health risks, including hepatocellular adenoma. Malignant transformation from hepatocellular adenoma to hepatocellular carcinoma after anabolic androgenic steroid abuse has been rarely reported. The morphological distinction of adenoma from well-differentiated hepatocellular carcinoma is challenging and requires elaborated imaging techniques and histology. CASE PRESENTATION: We report about a 29-year old male professional bodybuilder who presented with mid-epigastric pain at the emergency unit. Ultrasound showed a severe hepatomegaly with multiple lesions. Contrast-enhanced ultrasound revealed a heterogeneous pattern with signs of hepatocellular carcinoma. CT scan of the abdomen confirmed multiple hypervascular lesions and central areas of necrosis without contrast enhancement. Subsequent diagnostics included fine needle aspiration (FNA) of suspicious lesions and mini-laparoscopy to establish the diagnosis of a ß-catenin and testosterone-receptor positive hepatocellular carcinoma embedded in multiple adenomas. The patient was subsequently treated by liver transplantation and remains tumor-free 27 month after surgery. CONCLUSION: Hepatocellular carcinoma occurring in association with anabolic androgenic steroid abuse should sensitize physicians and especially professional bodybuilders for the harmful use of high doses of steroids.
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Anabolizantes/efectos adversos , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/inducido químicamente , Neoplasias Hepáticas/inducido químicamente , Sustancias para Mejorar el Rendimiento/efectos adversos , Receptores Androgénicos/metabolismo , Levantamiento de Peso , Adulto , Andrógenos/efectos adversos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Doping en los Deportes , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Masculino , Esteroides/efectos adversosRESUMEN
Background and aims: Bacterial cholangitis is a common complication in patients with ischemic type biliary lesions and/or anastomotic strictures after liver transplantation (LTX). Patients frequently need antibiotics and endoscopic retrograde cholangiography (ERC) to improve the bile flow. Antibiotic treatment is based on findings in standard microbiological cultivation (SMC) of bile. However, the cultivation techniques are limited to a subset of bacteria easy-to-cultivate. Therefore, the aim of our study was to evaluate the value of next generation sequencing as an additional diagnostic tool to SMC in ischemic type biliary lesions and/or anastomotic strictures. Methods: We sequenced the V1-V2 region of the 16S rRNA gene in 242 stored bile samples in patients after LTX and compared the results with findings of SMC. SMC was performed in n = 135 (56%) fresh bile samples in addition to NGS. SMC was part of the clinical routine in these patients. Results: NGS detected bacterial genera in bile samples more often than SMC (P = 5.42 × 10-74). SMC showed insufficient discovery of bacterial genera compared to NGS with better performance in patients receiving antibiotics prior to ERC. SMC missed many bacterial genera detected by NGS. Conclusions: NGS was more sensitive in detecting bacteria in bile than SMC, no clinical parameters could be used to improve discovery rates in SMC and many genera were missed by SMC. Therefore, NGS should be used in a combined approach with SMC for improved diagnostics to achieve more specific and targeted antibiotic treatments.
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OBJECTIVES: The objective of this study is to examine the comparative effectiveness of vancomycin and metronidazole in a confirmatory analysis of event-free survival (EFS) after initial infection in patients with Clostridioides difficile from a German multicentre cohort study. METHODS: The IBIS multicentre cohort enrolled patients with an index episode of C. difficile infection between August 2017 and September 2020. The primary endpoint was EFS, defined as response to treatment with metronidazole or vancomycin within 10 days of initiation, absence of recurrence and death from any cause up to 90 days post-treatment. A Cox proportional hazards model with inverse probability of treatment weighting was used to investigate the comparative effectiveness of this outcome. Additionally, subgroup analyses were performed based on severe and non-severe infections. RESULTS: Of the 489 patients included, 118 (24%) received initial treatment with metronidazole and 371 (76%) with vancomycin. Of these, 78/118 (66.1%) and 247/371 (66.6%), respectively, responded to treatment within 10 days, neither developed a recurrence nor died within 90 days and thus achieved the outcome of EFS. In the subgroup of non-severe infections, 74/293 patients (25.3%) received metronidazole, and 219/293 (74.7%) received vancomycin. Of these, 33/74 (44.6%) metronidazole patients and 150/219 (68.5%) vancomycin patients survived event free. The Cox proportional hazards model revealed differences in EFS for the overall population and both subgroups (reference metronidazole: all severity levels: hazard ratio [HR] 0.46, [95% CI, 0.33-0.65]; non-severe: HR 0.39; [95% CI, 0.24-0.60]; severe: HR 0.52; [95% CI, 0.28-0.95]). DISCUSSION: Our analysis confirms current changes in guidelines, as it supports the superiority of vancomycin compared with metronidazole across all severity levels.
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INTRODUCTION: Bile has long been considered sterile. Recent studies show that bacteria can frequently be detected in bile and certain bacterial species are associated with bile duct-associated liver disease. OBJECTIVES: To detect bacterial species and antibiotic resistance in bile in bile duct-associated liver disease. METHODOLOGY: To evaluate microbiological findings of bile samples obtained during ERCP at a tertiary center from 2009 to 2019. RESULTS: There were 1885 bile samples from 992 patients examined by cultural microbiological analysis. Germs were detected in 91% of the samples. Most bile samples (n) were obtained from patients who had undergone liver transplantation (LTX; nâ =â 556), followed by patients with primary sclerosing cholangitis (PSC; nâ =â 287). Enterococci were detected in 67% of samples, followed by E. coli (32.2%) and Klebsiella (28.2%). Of 1151 enterococci detected, 13.1% were vancomycin (VRE)s and of 216 staphylococci detected, 10% were ORSA. The proportion of VRE increased with the number of tests performed during ERCPs ( P â <â 0.01; chi-square) and increased 2.5-fold over 10 years, whereas the detection of ORSA remained stable. Patients with cholecystolithiasis were significantly more likely to have evidence of VRE in bile compared to LTX and PSC patients ( P â =â 0.02, P â <â 0.01; chi-square). The most abundant bacterial genera showed highly statistically significant differences in their levels of liver enzymes and c-reactive protein ( P â <â 0.001). CONCLUSION: Knowledge of the bacterial composition of bile in various bile duct-associated liver diseases may allow more targeted antibiotic use in the future.
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Colangitis Esclerosante , Hepatopatías , Microbiota , Humanos , Bilis/microbiología , Escherichia coli , Colangitis Esclerosante/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica , BacteriasRESUMEN
BACKGROUND: Accurate biomarkers for disease activity and progression in patients with inflammatory bowel disease (IBD) are a prerequisite for individual disease characterization and personalized therapy. We show that metabolic profiling of serum from IBD patients is a promising approach to establish biomarkers. The aim of this work was to characterize metabolomic and lipidomic serum profiles of IBD patients in order to identify metabolic fingerprints unique to the disease. METHODS: Serum samples were obtained from 55 patients with Crohn's disease (CD), 34 patients with ulcerative colitis (UC), and 40 healthy control (HC) individuals and analyzed using proton nuclear magnetic resonance spectroscopy. Classification of patients and HC individuals was achieved by orthogonal partial least squares discriminant analysis and univariate analysis approaches. Disease activity was assessed using the Gastrointestinal Symptom Rating Scale. RESULTS: Serum metabolome significantly differed between CD patients, UC patients, and HC individuals. The metabolomic differences of UC and CD patients compared with HC individuals were more pronounced than the differences between UC and CD patients. Differences in serum levels of pyruvic acid, histidine, and the branched-chain amino acids leucine and valine were detected. The size of low-density lipoprotein particles shifted from large to small dense particles in patients with CD. Of note, apolipoprotein A1 and A2 serum levels were decreased in CD and UC patients with higher fecal calprotectin levels. The Gastrointestinal Symptom Rating Scale is negatively associated with the concentration of apolipoprotein A2. CONCLUSIONS: Metabolomic assessment of serum samples facilitated the differentiation of IBD patients and HC individuals. These differences were constituted by changes in amino acid and lipoprotein levels. Furthermore, disease activity in IBD patients was associated with decreased levels of the atheroprotective apolipoproteins A1 and A2.
The metabolic and lipidomic serum profile of patients with inflammatory bowel disease was analyzed using proton nuclear magnetic resonance spectroscopy. A significantly altered profile in comparison with healthy control individuals was identified, characterized by more atherogenic properties.
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BACKGROUND: Fecal microbiota transfer (FMT) has become a standard of care in the prevention of multiple recurrent Clostridioides difficile (rCDI) infection. AIM: While primary cure rates range from 70-80% following a single treatment using monodirectional approaches, cure rates of combination treatment remain largely unknown. METHODS: In a retrospective case-control study, outcomes following simultaneous bidirectional FMT (bFMT) with combined endoscopic application into the upper and lower gastrointestinal tract, compared to standard routes of application (endoscopy via upper or lower gastrointestinal tract and oral capsules; abbreviated UGIT, LGIT and CAP) on day 30 and 90 after FMT were assessed. Statistical matching partners were identified using number of recurrences (<3; ≥3), age and gender. RESULTS: Primary cure rates at D30 and D90 for bFMT were 100% (p=.001). The matched control groups showed cure rates of 81.3% for LGIT (p=.010), 62.5% for UGIT (p=.000) and 78.1% for CAP (p=.005) on D30 and 81.3% for LGIT (p=.010), 59.4% for UGIT (p=.000) and 71.9% for CAP (p=.001) on D90. CONCLUSION: In our analysis, bFMT on the same day significantly increased primary cure rate at D30 and D90. These data require prospective confirmation but suggest that route of application may play a significant role in optimizing patient outcomes. ClinicalTrials.gov no: NCT02681068.
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Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal/métodos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Sistema de Registros , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: Faecal microbiota transplantation (FMT) has proven high clinical efficacy in the management of recurrent Clostridioides difficile infection (rCDI) with cure rates of over 80% after a single treatment. Nevertheless, the reasons for failure in the remaining 20% remain elusive. The aim of the present study was to investigate different potential predictors of response to FMT. METHODS: Faecal specimens of sixteen patients undergoing FMT for rCDI, as well as samples from the respective donors were collected and analyzed by 16S rRNA gene profiling, bile acid-inducible (baiCD) gene specific qPCR, and liquid chromatography tandem-mass spectrometry (LC-MS/MS) to quantify the concentrations of primary and secondary bile acids. RESULTS: Using the faecal concentration of the secondary bile acid lithocholic acid (LCA)within the patient specimens, we were able to predict response to FMT (accuracy 95.2%, sensitivity 100%, specificity 90.9%). By combining the faecal LCA concentration with the urinary pCS concentration, an accuracy of 100% was achieved. CONCLUSION: LCA appears to be a promising marker candidate for prediction of clinical response to FMT. Other makers, such as urinary concentration of pCS, but not 3-IS, might be used to improve accuracy of prediction. Further studies are warranted to validate these candidate markers.
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Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Ácido Litocólico/metabolismo , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Infecciones por Clostridium/microbiología , Heces/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del TratamientoRESUMEN
Introduction: Fecal microbiota transfer (FMT) is highly effective in the treatment and prevention of recurrent Clostridioides difficile infection (rCDI) with cure rates of about 80% after a single treatment. Nevertheless, the reasons for failure in the remaining 20% remain largely elusive. The aim of the present study was to investigate different potential clinical predictors of response to FMT in Germany. Methods: Information was extracted from the MicroTrans Registry (NCT02681068), a retrospective observational multicenter study, collecting data from patients undergoing FMT for recurrent or refractory CDI in Germany. We performed binary logistic regression with the following covariates: age, gender, ribotype 027, Eastern Co-operative Oncology Group score, immunosuppression, preparation for FMT by use of proton pump inhibitor, antimotility agents and bowel lavage, previous recurrences, severity of CDI, antibiotic induction treatment, fresh or frozen FMT preparation, and route of application. Results: Treatment response was achieved in 191/240 evaluable cases (79.6%) at day 30 (D30) post FMT and 78.1% at day 90 (D90) post FMT. Assessment of clinical predictors for FMT failure by forward and confirmatory backward-stepwise regression analysis yielded higher age as an independent predictor of FMT failure (p = 0.001; OR 1.060; 95%CI 1.025-1.097). Conclusion: FMT in Germany is associated with high cure rates at D30 and D90. No specific pre-treatment, preparation or application strategy had an impact on FMT success. Only higher age was identified as an independent risk factor for treatment failure. Based on these and external findings, future studies should focus on the assessment of microbiota and microbiota-associated metabolites as factors determining FMT success.