Carsten Schmidt

Universitätsklinikum Jena, Jena, Thuringia, Germany

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Publications (49)339.52 Total impact

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    ABSTRACT: Being among the most common cancers worldwide screening and early diagnosis of colorectal cancer is of high interest for the health system, the patients and for research. Raman microspectroscopy as a label-free, non-invasive and non-destructive technique is a promising tool for an early diagnosis. However, to ensure a reliable diagnosis specially designed statistical analysis workflows are required. Several statistical approaches have been introduced leading to varying results in the overall accuracy, sensitivity and specificity. In this study a systematic evaluation of different statistical analysis approaches has been performed using a colon cancer mouse model with genotypic identical individuals. Based on the inter-individual Raman spectral variances a measure for the biological variance can be estimated. By applying a leave-one-individual-out cross-validation a clinically relevant discrimination of healthy tissue versus adenoma and carcinoma with an accuracy of 95% is shown. Furthermore, the transfer of a model from tissue to biopsy specimen is demonstrated.
    No preview · Article · Dec 2015 · Journal of Biophotonics
  • Andreas Stallmach · Carsten Schmidt · Niels Teich
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    ABSTRACT: A substantial proportion of patients with ulcerative colitis (UC) have failed conventional therapies such as steroids, immunosuppressants and/or TNF-antibodies, or have experienced side effects. This article reviews the pharmacological properties of vedolizumab (VDZ), which is an α4β7 integrin inhibitor, and its efficacy and side effects in UC. By its relatively specific gut-selective mode of action of inhibiting leukocyte migration, VDZ's safety profile appears to be more favourable than that of anti-TNF therapies. VDZ is more effective than placebos for the induction and maintenance of remission in moderate to severe UC in both naïve patients and patients who have failed anti-TNF treatment. However, in some patients, VDZ has a slower onset of action, with a delayed clinical response. In summary, VDZ has increased the number of therapeutic options for UC; however, to place VDZ as a first-line therapy, it must go head-to-head with azathioprine and anti-TNF antibodies in future studies.
    No preview · Article · Nov 2015 · Expert Review of Gastroenterology and Hepatology
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    ABSTRACT: Background: The purpose of this study was to develop an automated image analysis algorithm to discriminate between head and neck cancer and nonneoplastic epithelium in confocal laser endomicroscopy (CLE) images. Methods: CLE was applied to image head and neck cancer epithelium in vivo. Histopathologic diagnosis from biopsies was used to classify the CLE images offline as cancer or noncancer tissue. The classified images were used to train automated software based on distance map histograms. The performance of the final algorithm was confirmed by "leave 2 patients out" cross-validation and area under the curve (AUC)/receiver operating characteristic (ROC) analysis. Results: Ninety-two CLE videos and 92 biopsies were analyzed from 12 patients. One hundred two frames of classified neoplastic tissue and 52 frames of nonneoplastic tissue were used for cross-validation of the developed algorithm. AUC varied from 0.52 to 0.92. Conclusion: The proposed software allows an objective classification of CLE images of head and neck cancer and adjacent nonneoplastic epithelium. © 2015 Wiley Periodicals, Inc. Head Neck, 2015.
    No preview · Article · Nov 2015 · Head & Neck
  • Martin B�rger · Carsten Schmidt · Niels Teich · Andreas Stallmach
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    ABSTRACT: Background: Medical therapy of mild and moderate ulcerative colitis (UC) of any extent is evidence-based and standardized by national and international guidelines. However, patients with steroid-refractory UC still represent a challenge. Methods: A literature search using PubMed (search terms: ulcerative colitis, therapy, new, 1-2008-2015) resulted in 821 publications. For the current article, 88 citations were extracted including 36 randomized controlled studies, 18 reviews, and 8 meta-analyses. Results: In steroid-refractory UC, early intensive therapy using anti-tumor necrosis factor (TNF) antibodies or the calcineurin inhibitors cyclosporine and tacrolimus is indicated in any case to prevent progression to a toxic megacolon and/or to avoid proctocolectomy. In patients with chronic disease activity, treatment with anti-TNF antibodies has a higher level of evidence than azathioprine therapy and should therefore be preferred. However, there is a subgroup of UC patients who may achieve prolonged steroid-free remission on azathioprine monotherapy. The importance of vedolizumab, a newly registered inhibiting antibody against integrin, has not yet been fully clarified since direct comparison studies are lacking, in particular in relation to anti-TNF antibodies. Conclusion: There is a great need for additional innovative therapies, especially in cases of primary non-response or secondary loss of response to anti-TNF antibodies. New small molecules (Janus kinase inhibitors) are promising with an acceptable safety profile and efficacy in UC. Further, strategies that target the intestinal microbiome are currently considered for patients with active or relapsing UC, and may in the future open up new therapeutic options.
    No preview · Article · Aug 2015 · Viszeralmedizin / Visceral Medicine
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    ABSTRACT: Cogan's syndrome (CSy) is a very rare autoimmune disorder, mainly affecting the inner ear and the eye, and is associated with inflammatory bowel disease (IBD). This was a European Crohn's and Colitis Organization (ECCO) retrospective observational study, performed as part of the CONFER project. A call to all ECCO members was made to report concomitant CSy and IBD cases. Clinical data were recorded in a standardized questionnaire. This international case series reports on 22 concomitant CSy-IBD cases from 14 large medical centers. Mean duration of IBD until diagnosis of CSy was 8.7 years (range 0.0-38.0), and mean age at CSy diagnosis was 44.6 years (range 9.0-67.0). 6 patients had an underlying ulcerative colitis (UC), 16 Crohn`s disease (CD). 11 patients (50%) had active disease at CSy diagnosis. 16 patients were under IBD treatments at the time of CSy diagnosis, of whom 6 (27.3%) were on anti-TNF. 7 out of 10 patients, who were treated for CSy with immunomodulators (mostly with corticosteroids), demonstrated at least partial response. This is the largest CSy-IBD case series so far. Although CSy is considered to be an autoimmune disease and is associated with IBD, immunomodulatory IBD maintenance treatment and even anti-TNF therapy do not seem to prevent disease onset. Moreover, IBD disease activity does not seem to trigger CSy. However, vigilance may prompt early diagnosis and directed intervention with corticosteriods at inception may potentially hinder audiovestibular deterioration. Finally, vigilance and awareness may also offer a better setting to study the pathophysiological mechanisms of this rare, but debilitating phenomena. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    No preview · Article · Jul 2015 · Journal of Crohn s and Colitis
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    ABSTRACT: Early detection of neoplastic lesions is essential in patients with long-standing ulcerative colitis but the best technique of colonoscopy is still controversial. We performed a prospective multicenter study in patients with long-standing ulcerative colitis. Two colonoscopies were performed in each patient within 3 weeks to 3 months. In white-light (WL) colonoscopy stepwise random biopsies (4 biopsies every 10cm), segmental random biopsies (2 biopsies in 5 segments) and targeted biopsies were taken. In NBI colonoscopy segmental and targeted biopsies were taken. The sequence of WL and NBI colonoscopy was randomized. In 36 of 159 patients enrolled (22.6%) 54 lesions with intraepithelial neoplasia (IN) were found (51 low-grade, 3 high-grade). In WL colonoscopy we found 11 IN in stepwise, 4 in segmental and 15 in targeted biopsies. In NBI colonoscopy 7 IN were detected in segmental and 24 IN in targeted biopsies. Almost all IN were found in one technique alone (Kappa value of WL versus NBI: -0.86, p<0.001). Statistically equivalent numbers of IN were found in NBI colonoscopy with targeted and segmental biopsies as in WL colonoscopy with targeted and stepwise biopsies but fewer biopsies (11.9 versus 38.6 biopsies, p<0.001) and less withdrawal time was necessary (23 versus 13 minutes, p<0.001). Stepwise biopsies are indispensable in WL colonoscopy. The combination of targeted and segmental biopsies in NBI technique is as sensitive as targeted together with stepwise biopsies in WL colonoscopy but requires fewer biopsies and less time. Highest sensitivity should be reached by combining WL and NBI technique by switching between the modes. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
    No preview · Article · May 2015 · Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association
  • Carsten Schmidt · Antje Besser · Iver Petersen · Andreas Stallmach

    No preview · Article · May 2015 · Gastrointestinal Endoscopy

  • No preview · Article · May 2015 · Gastrointestinal Endoscopy
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    ABSTRACT: Background and Aims: Inflammatory bowel diseases (IBD) are gaining increasing medical as well as economic significance. Improving medical treatment options can have a positive effect on number of hospitalized patients, necessary operations, or the inability to work. Methods: To understand patient-relevant endpoints in IBD, the 2000 to 2012 data published by the Federal Statistical Office and the 2012 data according to Article 21 of the Hospital Reimbursement Act were assessed. In addition, data records on the medication of IBD patients of a public health insurance company were evaluated. Results: During 2000-2012, the number of hospitalized IBD-patients (ICD 10 K50, K51) rose from 38,533 to 43,452 (+12.7%). The necessity of surgical intervention increased during the period under review. The number of people unable to work developed differently for Crohn's disease (CD) and ulcerative colitis (UC). CD shows an increase of 2.1%, and UC shows a decrease in inability-to-work cases of 9.5%. Entry of persons into the statutory pension insurance system did not decline from 2000 to 2012. The number of potential years of life lost (PYLL) in patients that suffer from IBD also remained constant during the period under review (2000-2002: 2017 PYLL vs. 2011 PYLL (2010-2012)). From 2009 to 2013 the percentage of patients treated with an anti-TNF-antibodies rose (2009: CD: 4.3%; UC: 1.4%; 2013: CD: 8.4%; UC: 3.2%). Discussion: A positive development for the patient-relevant endpoints was not observed between 2000 and 2012 in patients that suffer from IBD in Germany. Improvements can only be achieved through structured and overlapping treatment concepts involving all health care providers. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    No preview · Article · Mar 2015 · Journal of Crohn s and Colitis
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    ABSTRACT: Intestinal perforation or leakage increases morbidity and mortality of surgical and endoscopic interventions. We identified criteria for use of full-covered, extractable self-expanding metal stents (cSEMS) vs. 'Over the scope'-clips (OTSC) for leak closure. Patients who underwent endoscopic treatment for postoperative leakage, endoscopic perforation, or spontaneous rupture of the upper gastrointestinal tract between 2006 and 2013 were identified at four tertiary endoscopic centers. Technical success, outcome (e.g. duration of hospitalization, in-hospital mortality), and complications were assessed and analyzed with respect to etiology, size and location of leakage. Of 106 patients (male: 75 (71%), female: 31 (29%); age (mean ± SD): 62.5 ± 1.3 years, 72 (69%) were treated by cSEMS and 34 (31%) by OTSC. For cSEMS vs. OTSC, mean treatment duration was 41.1 vs. 25 days, p<0.001, leakage size 10 (1-50) vs. 5 (1-30) mm (median (range)), and complications were observed in 68% vs. 8.8%, p<0.001, respectively. Clinical success for primary interventional treatment was observed in 29/72 (40%) vs. 24/34 (70%, p = 0.006), and clinical success at the end of follow-up was 46/72 (64%) vs. 29/34 (85%) for patients treated by cSEMS vs. OTSC; p = 0.04. OTSC is preferred in small-sized lesions and in perforation caused by endoscopic interventions, cSEMS in patients with concomitant local infection or abscess. cSEMS is associated with a higher frequency of complications. Therefore, OTSC might be preferred if technically feasible. Indication criteria for cSEMS vs. OTSC vary and might impede design of randomized studies.
    Full-text · Article · Jan 2015 · PLoS ONE
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    ABSTRACT: Aim: To detect high risk patients with a progressive disease course of ulcerative colitis (UC) requiring immunosuppressive therapy (IT). Methods: A retrospective, multicenter analysis of 262 UC patients from eight German tertiary inflammatory bowel disease centres was performed. Patients were divided into two groups depending on the patients need to initiate immunosuppressive therapy in the disease course. A comparison between the two groups was made with regard to demographics, clinical and laboratory parameters obtained within three months after UC diagnosis and the response to first medical therapy. Using this data, a prognostic model was established to predict the individual patients probability of requiring an immunosuppressive therapy. Results: In 104 (39.7%) out of 262 patients, UC therapy required an immunosuppressive treatment. Patients in this group were significantly younger at time of diagnosis (HR = 0.981 ± 0.014 per year, P = 0.009), and required significantly more often a hospitalisation (HR = 2.5 ± 1.0, P < 0.001) and a systemic corticosteroid therapy at disease onset (HR = 2.4 ± 0.8, P < 0.001), respectively. Response to steroid treatment was significantly different between the two groups of patients (HR = 5.2 ± 3.9 to 50.8 ± 35.6 compared to no steroids, P = 0.016 to P < 0.001). Furthermore, in the IT group an extended disease (HR = 3.5 ± 2.4 to 6.1 ± 4.0 compared to proctitis, P = 0.007 to P = 0.001), anemia (HR = 2.2 ± 0.8, P < 0.001), thrombocytosis (HR = 1.9 ± 1.8, P = 0.009), elevated C-reactive protein (CRP) (HR = 2.1 ± 0.9, P < 0.001), and extraintestinal manifestations in the course of disease (HR = 2.6 ± 1.1, P = 0.004) were observed. Six simple clinical items were used to establish a prognostic model to predict the individual risk requiring an IT. This probability ranges from less than 2% up to 100% after 5 years. Using this, the necessity of an immunosuppressive therapy can be predicted in 60% of patients. Our model can determine the need for an immunosuppressive drug therapy or if a "watch and wait" approach is reasonable already early in the treatment course of UC. Conclusion: Using six simple clinical parameters, we can estimate the patients individual risk of developing a progressive disease course.
    Full-text · Article · Sep 2014 · World Journal of Gastroenterology

  • No preview · Article · May 2014 · Gastrointestinal Endoscopy

  • No preview · Article · May 2014 · Gastroenterology

  • No preview · Article · May 2014 · Gastroenterology

  • No preview · Article · May 2014

  • No preview · Article · May 2014 · Gastrointestinal Endoscopy
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    ABSTRACT: Inflammatory bowel disease (IBD) is a frequently occurring disease in young people, which is characterized by a chronic inflammation of the gastrointestinal tract. The therapy of IBD is dominated by the administration of anti-inflammatory and immunosuppressive drugs, which suppress the intestinal inflammatory burden and improve the disease-related symptoms. Established treatment strategies are characterized by a limited therapeutical efficacy and the occurrence of adverse drug reactions. Thus, the development of novel disease-targeted drug delivery strategies is intended for a more effective therapy and demonstrates the potential to address unmet medical needs. This review gives an overview about the established as well as future-oriented drug targeting strategies, including intestine targeting by conventional drug delivery systems (DDS), disease targeted drug delivery by synthetic DDS and disease targeted drug delivery by biological DDS. Furthermore, this review analyzes the targeting mechanisms of the respective DDS and discusses the possible field of utilization in IBD.
    No preview · Article · Oct 2013 · Advanced drug delivery reviews
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    ABSTRACT: The systemic therapy of inflammatory bowel diseases (IBD) by oral administration of anti-inflammatory and immunosuppressive agents is characterized by an increased probability of adverse drug reactions. A successful treatment with a simultaneous reduction of adverse events may be achieved by the administration of micro- and nanosized targeted drug delivery systems, which accumulate selectively in inflamed mucosal areas without systemic absorption. We described in a first in vivo study in IBD patients a significantly enhanced, but minor accumulation of non-functionalized poly(lactic-co-glycolic acid) (PLGA) microparticles in ulcerous lesions very recently. The aim of this study was therefore the assessment of an increased targeting potential of different non-, chitosan- and polyethylene glycol (PEG)-functionalized PLGA micro- and nanoparticles to inflamed intestinal mucosa compared to healthy mucosa. For the quantification of nano- and microparticles, fluoresceinamine-labeled-PLGA was synthesized by carbodiimide reaction. Fluorescent chitosan-, PEG-, and non-functionalized PLGA micro- and nanoparticles with mean hydrodynamic diameters of 3000 nm and 300 nm were prepared by solvent evaporation technique. The targeting efficiencies in terms of particle translocation and deposition were investigated in Ussing chamber experiments. Healthy and inflamed macrobiopsies were received from routine endoscopic examinations of patients with IBD as well as control patients. 101 Ussing chamber experiments of patients with IBD (Crohńs disease: n = 7 and ulcerative colitis: n = 9) as well as healthy control patients (n=5) were performed. Histomorphological and electrophysiological investigations of inflamed mucosal tissues confirmed a significant alteration of mucosal barrier integrity in IBD patients (TER: healthy: 34.1 Ω x cm(2); inflamed: 21.6 Ω x cm(2); p=0.034). In summary, nanoparticles showed an increased translocation and deposition compared to microparticles in healthy and in inflamed mucosa. Chitosan-functionalized particles adhered onto the tissue surface and thus showed the lowest particle translocation and deposition in healthy and inflamed tissues. PEG-functionalized nanoparticles showed the highest translocation through healthy (2.31%) and inflamed mucosa (5.27%). Moreover, PEG-functionalized microparticles showed a significantly increased translocation through inflamed mucosa (3.33%) compared to healthy mucosa (0.55%; p=0.045). Notably, the particle deposition of PEG-functionalized microparticles was significantly increased in inflamed mucosa (10.8%) compared to healthy mucosa (4.1%; p=0.041). Based on the targeted translocation and deposition to inflamed intestinal mucosa, PEG-functionalized PLGA microparticles were qualified as an innovative drug delivery system. These particles may serve as a selective treatment strategy to inflamed mucosal areas in IBD with the potential to improve therapeutic efficacy and to reduce adverse events.
    Full-text · Article · Sep 2013 · European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
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    ABSTRACT: Inflammatory bowel disease (IBD), commonly known as Crohn's disease and ulcerative colitis, is a frequently occurring disease in Gastroenterology, which is characterized by a chronic intestinal inflammatory ailment. The therapy of IBD is dominated by the administration of anti-inflammatory and immune-modulating drugs, which suppress the intestinal inflammation and thus improve disease-related symptoms. The enhanced insight and more detailed knowledge about the pathophysiological mechanisms of IBD accelerate the research and development of innovative drugs and new treatment strategies. In the last decades, many evolutionary as well as revolutionary innovations were developed and investigated in clinical trials. This review is believed to give an overview about established and future-orientated treatment approaches, including antisense gene therapy, non-embryonic stem cell therapy, leucocytapheresis and faecal biotherapy. Additionally, this review illuminates other smaller clinical trials, which follow interesting and maverick approaches, like lecithinmediated mucosal healing, Trichuris suis ova-supported treatment or several herbal treatment strategies. The main focus is pointed in the conceivable explanation of the respective molecular target mechanisms as well as potential to modulate the inflammatory and immunological process. Additionally, this review gives a brief insight in the therapeutical benefits and mediates about the risks of the respective treatment approaches.
    No preview · Article · Sep 2013 · Current Drug Therapy
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    Full-text · Article · May 2013 · Gastrointestinal Endoscopy

Publication Stats

823 Citations
339.52 Total Impact Points

Institutions

  • 2012-2015
    • Universitätsklinikum Jena
      Jena, Thuringia, Germany
  • 2007-2011
    • Friedrich-Schiller-University Jena
      • Clinic of Internal Medicine II
      Jena, Thuringia, Germany
  • 2002-2005
    • Universität des Saarlandes
      Saarbrücken, Saarland, Germany