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  1. Article ; Online: Making sense of regulatory T cell suppressive function.

    Shalev, Itay / Schmelzle, Moritz / Robson, Simon C / Levy, Gary

    Seminars in immunology

    2011  Volume 23, Issue 4, Page(s) 282–292

    Abstract: Several types of regulatory T cells maintain self-tolerance and control excessive immune responses ... to foreign antigens. The major regulatory T subsets described over the past decade and novel function ... in transplantation will be covered in this review with a focus on CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells ...

    Abstract Several types of regulatory T cells maintain self-tolerance and control excessive immune responses to foreign antigens. The major regulatory T subsets described over the past decade and novel function in transplantation will be covered in this review with a focus on CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells. Multiple mechanisms have been proposed to explain how Treg cells inhibit effector cells but none can completely explain the observed effects in toto. Proposed mechanisms to explain suppressive activity of Treg cells include the generation of inhibitory cytokines, induced death of effector cells by cytokine deprivation or cytolysis, local metabolic perturbation of target cells mediated by changes in extracellular nucleotide/nucleoside fluxes with alterations in intracellular signaling molecules such as cyclic AMP, and finally inhibition of dendritic cell functions. A better understanding of how Treg cells operate at the molecular level could result in novel and safer therapeutic approaches in transplantation and immune-mediated diseases.
    MeSH term(s) Animals ; Apoptosis/immunology ; CD4 Antigens ; Cyclic AMP/immunology ; Cyclic AMP/metabolism ; Dendritic Cells/physiology ; Forkhead Transcription Factors ; Humans ; Immune Tolerance ; Immunosuppression ; Interleukin-2 Receptor alpha Subunit ; Membrane Potentials/immunology ; Paracrine Communication/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/immunology ; Transplantation Immunology
    Chemical Substances CD4 Antigens ; FOXP3 protein, human ; Forkhead Transcription Factors ; Interleukin-2 Receptor alpha Subunit ; Cyclic AMP (E0399OZS9N)
    Language English
    Publishing date 2011-05-17
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1018141-6
    ISSN 1096-3618 ; 1044-5323
    ISSN (online) 1096-3618
    ISSN 1044-5323
    DOI 10.1016/j.smim.2011.04.003
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  2. Article: Making sense of regulatory T cell suppressive function

    Shalev, Itay / Schmelzle, Moritz / Robson, Simon C / Levy, Gary

    Seminars in immunology. 2011 Aug., v. 23, no. 4

    2011  

    Abstract: Several types of regulatory T cells maintain self-tolerance and control excessive immune responses ... to foreign antigens. The major regulatory T subsets described over the past decade and novel function ... in transplantation will be covered in this review with a focus on CD4+CD25+Foxp3+ regulatory T (Treg) cells. Multiple ...

    Abstract Several types of regulatory T cells maintain self-tolerance and control excessive immune responses to foreign antigens. The major regulatory T subsets described over the past decade and novel function in transplantation will be covered in this review with a focus on CD4+CD25+Foxp3+ regulatory T (Treg) cells. Multiple mechanisms have been proposed to explain how Treg cells inhibit effector cells but none can completely explain the observed effects in toto. Proposed mechanisms to explain suppressive activity of Treg cells include the generation of inhibitory cytokines, induced death of effector cells by cytokine deprivation or cytolysis, local metabolic perturbation of target cells mediated by changes in extracellular nucleotide/nucleoside fluxes with alterations in intracellular signaling molecules such as cyclic AMP, and finally inhibition of dendritic cell functions. A better understanding of how Treg cells operate at the molecular level could result in novel and safer therapeutic approaches in transplantation and immune-mediated diseases.
    Keywords T-lymphocytes ; adenosine monophosphate ; antigens ; cyclic AMP ; cytokines ; cytolysis ; death ; immune response ; nucleosides
    Language English
    Dates of publication 2011-08
    Size p. 282-292.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 1018141-6
    ISSN 1096-3618 ; 1044-5323
    ISSN (online) 1096-3618
    ISSN 1044-5323
    DOI 10.1016/j.smim.2011.04.003
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  3. Article ; Online: Pulmonary natural killer T cells play an essential role in mediating hyperoxic acute lung injury.

    Nowak-Machen, Martina / Schmelzle, Moritz / Hanidziar, Dusan / Junger, Wolfgang / Exley, Mark / Otterbein, Leo / Wu, Yan / Csizmadia, Eva / Doherty, Glen / Sitkovsky, Michail / Robson, Simon C

    American journal of respiratory cell and molecular biology

    2013  Volume 48, Issue 5, Page(s) 601–609

    Abstract: ... of the tissue-damaging effects of oxygen in mice. We show that pulmonary invariant natural killer T (iNKT) cells ...

    Abstract Critically ill patients are routinely exposed to high concentrations of supplemental oxygen for prolonged periods of time, which can be life-saving in the short term, but such exposure also causes severe lung injury and increases mortality. To address this therapeutic dilemma, we studied the mechanisms of the tissue-damaging effects of oxygen in mice. We show that pulmonary invariant natural killer T (iNKT) cells are unexpectedly crucial in the development of acute oxygen-induced lung injury. iNKT cells express high concentrations of the ectonucleotidase CD39, which regulates their state of activation. Both iNKT cell-deficient (Jα18(-/-)) and CD39-null mice tolerate hyperoxia, compared with wild-type control mice that exhibit severe lung injury. An adoptive transfer of wild-type iNKT cells into Jα18(-/-) mice results in hyperoxic lung injury, whereas the transfer of CD39-null iNKT cells does not. Pulmonary iNKT cell activation and proliferation are modulated by ATP-dependent purinergic signaling responses. Hyperoxic lung injury can be induced by selective P2X7-receptor blockade in CD39-null mice. Our data indicate that iNKT cells are involved in the pathogenesis of hyperoxic lung injury, and that tissue protection can be mediated through ATP-induced P2X7 receptor signaling, resulting in iNKT cell death. In conclusion, our data suggest that iNKT cells and purinergic signaling should be evaluated as potential novel therapeutic targets to prevent hyperoxic lung injury.
    MeSH term(s) Acute Lung Injury/etiology ; Acute Lung Injury/immunology ; Acute Lung Injury/pathology ; Adoptive Transfer ; Animals ; Antigens, CD/genetics ; Antigens, CD/metabolism ; Apoptosis ; Apyrase/genetics ; Apyrase/metabolism ; Cell Proliferation ; Cells, Cultured ; Cytokines/metabolism ; Hyperoxia/complications ; Hyperoxia/immunology ; Hyperoxia/pathology ; Lung/immunology ; Lung/pathology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Natural Killer T-Cells/enzymology ; Natural Killer T-Cells/immunology ; Natural Killer T-Cells/physiology ; Neutrophil Infiltration ; Neutrophils/immunology ; Neutrophils/metabolism
    Chemical Substances Antigens, CD ; Cytokines ; Apyrase (EC 3.6.1.5) ; CD39 antigen (EC 3.6.1.5)
    Language English
    Publishing date 2013-02-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1025960-0
    ISSN 1535-4989 ; 1044-1549
    ISSN (online) 1535-4989
    ISSN 1044-1549
    DOI 10.1165/rcmb.2012-0180OC
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  4. Book ; Thesis: Differentialtherapie des kardiogenen Schocks mit Dopamin, Milrinon im Vergleich zu Dopamin, Dobutamin

    Schmelzle, Thomas

    1998  

    Author's details vorgelegt von Thomas Schmelzle
    Language German
    Size 68 S. : graph. Darst.
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Kiel, Univ., Diss., 1998
    HBZ-ID HT010084649
    Database Catalogue ZB MED Medicine, Health

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  5. Article ; Online: Risk factors for malignant transformation of hepatocellular adenoma to hepatocellular carcinoma: protocol for systematic review and meta-analysis.

    Thevathasan, Tharusan / Colbatzky, Teresa / Schmelzle, Moritz / Pratschke, Johann / Krenzien, Felix

    BMJ open

    2021  Volume 11, Issue 8, Page(s) e045733

    Abstract: Introduction: Hepatocellular adenomas (HCAs) are solid liver tumours that are usually found incidentally during routine medical check-ups. Multiple modifiable and non-modifiable factors constitute a risk for the malignant transformation of HCAs to ... ...

    Abstract Introduction: Hepatocellular adenomas (HCAs) are solid liver tumours that are usually found incidentally during routine medical check-ups. Multiple modifiable and non-modifiable factors constitute a risk for the malignant transformation of HCAs to hepatocellular carcinoma (HCC), which has emerged to be one of the fastest growing causes of cancer-related mortality globally. This study protocol for a planned systematic review and meta-analysis documents the methodological approach to identify risk factors and their risk estimates for the transformation from HCA to HCC.
    Methods and analysis: Two independent reviewers will systematically search and extract data from studies in patients of all ages published between January 1970 and June 2021 on PubMed, MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Scopus Web of Science, Ovid, The Cochrane Hepatobiliary Group Controlled Trials Register and The Cochrane Central Register of Controlled Trials by using an
    Ethics and dissemination: No ethical approval is required as we will use and analyse data from previously published studies in which informed consent was obtained. The results will be disseminated in a peer-reviewed journal on completion.
    Prospero registration number: CRD42020206578.
    MeSH term(s) Adenoma, Liver Cell ; Carcinoma, Hepatocellular/epidemiology ; Carcinoma, Hepatocellular/etiology ; Humans ; Liver Neoplasms/epidemiology ; Liver Neoplasms/etiology ; Meta-Analysis as Topic ; Research Design ; Risk Factors ; Systematic Reviews as Topic
    Language English
    Publishing date 2021-08-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2020-045733
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  6. Article ; Online: Teaching und Training in der robotergestützten Chirurgie.

    Schmelzle, Moritz / Malinka, Thomas / Bahra, Marcus / Pratschke, Johann

    Zentralblatt fur Chirurgie

    2020  Volume 145, Issue 3, Page(s) 271–277

    Abstract: The development and proliferation of robot-assisted surgery has greatly extended the field of minimally invasive surgery. Thus, this necessitates the development of adequate training programs to prepare surgeons for the operating room of the future. ... ...

    Title translation Teaching and Training in Robot-assisted Surgery.
    Abstract The development and proliferation of robot-assisted surgery has greatly extended the field of minimally invasive surgery. Thus, this necessitates the development of adequate training programs to prepare surgeons for the operating room of the future. Transferring established and proven methods of training and assessment in aviation could help robotic training programs become more effective, efficient and safer. Simulation is a safe and cost-effective way of training and in addition may improve operating room performance. Proctoring and flying doctor models are established concepts, especially for advanced training. This review summarises current developments in robotic surgical training and teaching and may help to start a controversial discussion.
    MeSH term(s) Humans ; Robotic Surgical Procedures ; Surveys and Questionnaires
    Language German
    Publishing date 2020-06-04
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 200935-3
    ISSN 1438-9592 ; 0044-409X
    ISSN (online) 1438-9592
    ISSN 0044-409X
    DOI 10.1055/a-1156-4357
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  7. Article ; Online: Gallengangsverletzung im Rahmen der laparoskopischen Cholezystektomie : Klassifikation, Erkennung und Reparation.

    Nevermann, Nora / Schöning, Wenzel / Malinka, Thomas / Fehrenbach, Uli / Müller, Tobias / Pratschke, Johann / Schmelzle, Moritz

    Chirurgie (Heidelberg, Germany)

    2022  Volume 93, Issue 6, Page(s) 554–565

    Abstract: Background: Bile duct injuries during laparoscopic cholecystectomy are rare but serious complications.: Classification and diagnostics: Bile duct injuries can be classified based on their location, injury pattern and possible concomitant vascular ... ...

    Title translation Bile duct injuries during laparoscopic cholecystectomy : Classification, recognition and repair.
    Abstract Background: Bile duct injuries during laparoscopic cholecystectomy are rare but serious complications.
    Classification and diagnostics: Bile duct injuries can be classified based on their location, injury pattern and possible concomitant vascular injury. Several classifications exist with the Neuhaus classification, which is widely used in Germany, allowing a clinically oriented classification of bile duct injuries. The diagnostic algorithm is based on whether the injury is diagnosed due to bile leakage or bile duct occlusion and whether there is also a circulatory disturbance of the liver. The differentiated use of laboratory, image-based, endoscopic and interventional methods enables not only classification but also treatment planning.
    Treatment: About half of all bile duct lesions can be treated by an endoscopic intervention; however, with increasing size of the defect, with complete occlusion of the bile duct or with relevant circulatory disturbances of the liver, the probability for the need of a surgical procedure increases. Intraoperatively, a distinction must be made between repair by suturing and splinting and reconstruction of the bile duct by patch plasty or hepaticojejunostomy. Partial liver resection or liver transplantation may be necessary, especially in cases of circulatory disorders. In addition to appropriate experience, good communication and interdisciplinary cooperation between endoscopy, interventional radiology and surgery are crucial for the success of the treatment. In this respect, contacting a specialized center for liver and transplantation surgery as soon as possible is advised.
    MeSH term(s) Abdominal Injuries/surgery ; Bile Ducts/diagnostic imaging ; Cholecystectomy, Laparoscopic/adverse effects ; Cholestasis/surgery ; Humans ; Liver Transplantation
    Language German
    Publishing date 2022-02-16
    Publishing country Germany
    Document type Journal Article ; Review
    ISSN 2731-698X
    ISSN (online) 2731-698X
    DOI 10.1007/s00104-022-01592-0
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  8. Article ; Online: MR imaging of hepatocellular carcinoma: prospective intraindividual head-to-head comparison of the contrast agents gadoxetic acid and gadoteric acid.

    Collettini, Federico / Elkilany, Aboelyazid / Seta, Marta Della / Steffen, Ingo G / Collettini, Jasmin Maya / Penzkofer, Tobias / Schmelzle, Moritz / Denecke, Timm

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 18583

    Abstract: ... Twenty-three patients with liver cirrhosis and proven HCC underwent two 3 T-MR examinations, one with ECA ...

    Abstract The routine use of dynamic-contrast-enhanced MRI (DCE-MRI) of the liver using hepatocyte-specific contrast agent (HSCA) as the standard of care for the study of focal liver lesions is not widely accepted and opponents invoke the risk of a loss in near 100% specificity of extracellular contrast agents (ECA) and the need for prospective head-to-head comparative studies evaluating the diagnostic performance of both contrast agents. The Purpose of this prospective intraindividual study was to conduct a quantitative and qualitative head-to-head comparison of DCE-MRI using HSCA and ECA in patients with liver cirrhosis and HCC. Twenty-three patients with liver cirrhosis and proven HCC underwent two 3 T-MR examinations, one with ECA (gadoteric acid) and the other with HSCA (gadoxetic acid). Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), wash-in, wash-out, image quality, artifacts, lesion conspicuity, and major imaging features of LI-RADS v2018 were evaluated. Wash-in and wash-out were significantly stronger with ECA compared to HSCA (P < 0.001 and 0.006, respectively). During the late arterial phase (LAP), CNR was significantly lower with ECA (P = 0.005), while SNR did not differ significantly (P = 0.39). In qualitative analysis, ECA produced a better overall image quality during the portal venous phase (PVP) and delayed phase (DP) compared to HSCA (P = 0.041 and 0.008), showed less artifacts in the LAP and PVP (P = 0.003 and 0.034) and a higher lesion conspicuity in the LAP and PVP (P = 0.004 and 0.037). There was no significant difference in overall image quality during the LAP (P = 1), in artifacts and lesion conspicuity during the DP (P = 0.078 and 0.073) or in the frequency of the three major LI-RADS v2018 imaging features. In conclusion, ECA provides superior contrast of HCC-especially hypervascular HCC lesions-in DCE-MR in terms of better perceptibility of early enhancement and a stronger washout.
    MeSH term(s) Humans ; Carcinoma, Hepatocellular/diagnostic imaging ; Contrast Media ; Prospective Studies ; Liver Neoplasms/diagnostic imaging ; Gadolinium DTPA ; Magnetic Resonance Imaging/methods ; Liver Cirrhosis ; Chelating Agents ; Sensitivity and Specificity ; Retrospective Studies
    Chemical Substances gadolinium ethoxybenzyl DTPA ; Contrast Media ; Gadolinium DTPA (K2I13DR72L) ; Chelating Agents
    Language English
    Publishing date 2022-11-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-23397-1
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  9. Article: Implementation of Robotic Assistance in Pancreatic Surgery: Experiences from the First 101 Consecutive Cases.

    Timmermann, Lea / Biebl, Matthias / Schmelzle, Moritz / Bahra, Marcus / Malinka, Thomas / Pratschke, Johann

    Journal of clinical medicine

    2021  Volume 10, Issue 2

    Abstract: Robotic assisted minimally invasive surgery has been implemented to overcome typical limitations of conventional laparoscopy such as lack of angulation, especially during creation of biliary and pancreatic anastomoses. With this retrospective analysis, ... ...

    Abstract Robotic assisted minimally invasive surgery has been implemented to overcome typical limitations of conventional laparoscopy such as lack of angulation, especially during creation of biliary and pancreatic anastomoses. With this retrospective analysis, we provide our experience with the first 101 consecutive robotic pancreatic resection performed at our center. Distal pancreatectomies (RDP, N = 44), total pancreatectomies (RTP, N = 3) and pancreaticoduodenectomies (RPD, N = 54) were included. Malignancy was found in 45.5% (RDP), 66.7% (RTP) and 61% (RPD). Procedure times decreased from the first to the second half of the cohort for RDP (218 min vs. 128 min,
    Language English
    Publishing date 2021-01-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm10020229
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  10. Article ; Online: Challenges of single-stage pancreatoduodenectomy: how to address pancreatogastrostomies with robotic-assisted surgery.

    Timmermann, Lea / Hillebrandt, Karl Herbert / Felsenstein, Matthäus / Schmelzle, Moritz / Pratschke, Johann / Malinka, Thomas

    Surgical endoscopy

    2021  Volume 36, Issue 9, Page(s) 6361–6367

    Abstract: Introduction: Establishing a sufficient pancreatico-enteric anastomosis remains one of the most important challenges in open single stage pancreatoduodenectomy as they are associated with persisting morbidity and mortality. Applicability on a robotic- ... ...

    Abstract Introduction: Establishing a sufficient pancreatico-enteric anastomosis remains one of the most important challenges in open single stage pancreatoduodenectomy as they are associated with persisting morbidity and mortality. Applicability on a robotic-assisted approach, however, even increases the requirements. With this analysis we introduce a dorsal-incision-only invagination type pancreatogastrostomy (dioPG) to the field of robotic assistance having been previously proven feasible in the field of open pancreatoduodenectomy and compare initial results to the open approach by means of morbidity and mortality.
    Methods: An overall of 142 consecutive patients undergoing reconstruction via the novel dioPG, 38 of them in a robotic-assisted and 104 in an open approach, was identified and further reviewed for perioperative parameters, complications and mortality.
    Results: We observed a comparable R0-resection rate (p = 0.448), overall complication rate (p = 0.52) and 30-day mortality (p = 0.71) in both groups. Rates of common complications, such as postoperative pancreatic fistula (p = 0.332), postoperative pancreatic hemorrhage (p = 0.242), insufficiency of pancreatogastrostomy (p = 0.103), insufficiency of hepaticojejunostomy (p = 0.445) and the re-operation rate (p = 0.103) were comparable. The procedure time for the open approach was significantly shorter compared to the robotic-assisted approach (p = 0.024).
    Discussion: The provided anastomosis appeared applicable to a robotic-assisted setting resulting in comparable complication and mortality rates when compared to an open approach. Nevertheless, also in the field of robotic assistance establishing a predictable pancreatico-enteric anastomosis remains the most challenging aspect of modern single-stage pancreatoduodenectomy and requires expertise and experience.
    MeSH term(s) Anastomosis, Surgical/adverse effects ; Humans ; Pancreas/surgery ; Pancreatic Fistula/complications ; Pancreatic Fistula/etiology ; Pancreaticoduodenectomy/adverse effects ; Pancreaticoduodenectomy/methods ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology ; Postoperative Complications/surgery ; Postoperative Hemorrhage/surgery ; Robotic Surgical Procedures/adverse effects
    Language English
    Publishing date 2021-12-09
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639039-0
    ISSN 1432-2218 ; 0930-2794
    ISSN (online) 1432-2218
    ISSN 0930-2794
    DOI 10.1007/s00464-021-08925-w
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