W Padberg

Vitos Gießen-Marburg, Giessen, Hesse, Germany

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Publications (165)359.48 Total impact

  • Source
    C Koch · A Hecker · V Grau · W Padberg · M Wolff · M Henrich
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    ABSTRACT: Necrotizing fasciitis (NF) is an inflammatory disease of the soft tissue, which causes local tissue destruction and can lead to lethal septic shock. The therapy consists of early surgical treatment of the septic focus and an accompanying broad spectrum antibiotic therapy. Recent literature considers the additional use of immunoglobulin therapy in severe soft skin and tissue infections. In this report, we describe the case of a 33-year-old male patient treated at a university hospital intensive care unit because of an NF of his left leg. The patient rapidly developed a complicated septic disease after a minor superficial trauma. Despite intense microbiological diagnosis, no causative pathogens were identified. After non-responding to established broad anti-infective treatment, the patient received intravenous immunoglobulin, that rapidly improved his clinical condition. NF represents a disease processes, which is characterized by fulminant, widespread necrosis of soft tissue, systemic toxicity, and high mortality (>30%). Beside the surgical debridement and broad spectrum antibiotic therapy IVIg therapy might be an additional option in the treatment of NF. But the current literature supporting the use of IVIG in NF is largely based on retrospective or case-controlled studies, and only small randomized trials. The demonstrated case suggests that IVIg treatment of patients with NF can be considered in case of hemodynamic unstable, critically ill patients. Although randomized controlled trials are missing, some patients might benefit from diminishing hyperinflammation by immunoglobins.
    Annals of Medicine and Surgery 09/2015; 4(3):260-3. DOI:10.1016/j.amsu.2015.07.017
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    ABSTRACT: Purpose: Resection rectopexy (RR) provides good functional results and low recurrence rates for the treatment of obstructed defecation syndrome based on rectal prolapse and cul-de-sac syndrome, whereas little is known about changes in pelvic floor dynamics and patient satisfaction after surgery. Materials and Methods: Within three years 26 consecutive female patients were prospectively included. Indications for RR (22 laparoscopic, 3 primary open and 1 converted-to-open) were rectal prolapse III° in 11 patients and cul-de-sac syndrome in 15 patients. Patients' quality of life (QOL), fecal behavior and defecation-associated pain were investigated before and after surgical treatment using anamnesis and clinical examination, Rand 36-idem health survey (SF-36), Cleveland-Clinic Incontinence Score (CCIS) and the visual analog scale for defecation-associated pain (VAS). Dynamic pelvic floor magnet resonance imaging (dPF-MRI) was used for the investigation of changes in pelvic floor anatomy and function before and after surgery. Results: RR improved the rate of fecal incontinence (p < 0.01) and CCIS (p = 0.01). The use of laxatives (p = 0.01), the need for self-digitation (p = 0.02) and VAS (p < 0.01) were decreased, leading to improvements in QOL (overall p < 0.01). RR led to shortening of the H-line but not of the M-line under rest (p < 0.01) and during defecation (p = 0.04). A rectocele was co-incident in all patients in dPF-MRI before surgery. RR led to a reduction (p < 0.01) and declined protrusion (p = 0.03) of the rectocele. This results in a decreased rate of cul-de-sac (p < 0.01) and increased rate of complete defecation (p < 0.01) after surgery. At the 36-month follow-up no recurrence was observed. Conclusion: RR promises high rates of patient satisfaction and improvement in pelvic floor anatomy in select patients. Key Points: • RR improves the pelvic floor anatomy of patients suffering from ODS• RR improves the QOL of patients suffering from ODS• An improvement in pelvic floor anatomy led to an improved QOL• RR is an adequate treatment for select patients suffering from ODS Citation Format: • Reichert M, Busse A, Hecker A et al. Changes in Dynamic Pelvic Floor Magnet Resonance Imaging and Patient Satisfaction after Resection Rectopexy for Obstructed Defecation Syndrome. Fortschr Röntgenstr 2015; DOI: 10.1055/s-0041-105406. © Georg Thieme Verlag KG Stuttgart · New York.
    RöFo - Fortschritte auf dem Gebiet der R 09/2015; DOI:10.1055/s-0041-105406 · 1.40 Impact Factor
  • A Busse · E Schneck · C Koch · R Röhrig · G Krombach · M Weigand · F Roller · W Padberg
    Zeitschrift für Gastroenterologie 08/2015; 53(08). DOI:10.1055/s-0035-1559456 · 1.05 Impact Factor
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    ABSTRACT: IL-1β is a potent proinflammatory cytokine of the innate immune system that is involved in host defense against infection. However, increased production of IL-1β plays a pathogenic role in various inflammatory diseases, such as rheumatoid arthritis, gout, sepsis, stroke, and transplant rejection. To prevent detrimental collateral damage, IL-1β release is tightly controlled and typically requires two consecutive danger signals. LPS from Gram-negative bacteria is a prototypical first signal inducing pro-IL-1β synthesis, whereas extracellular ATP is a typical second signal sensed by the ATP receptor P2X7 that triggers activation of the NLRP3-containing inflammasome, proteolytic cleavage of pro-IL-1β by caspase-1, and release of mature IL-1β. Mechanisms controlling IL-1β release, even in the presence of both danger signals, are needed to protect from collateral damage and are of therapeutic interest. In this article, we show that acetylcholine, choline, phosphocholine, phosphocholine-modified LPS from Haemophilus influenzae, and phosphocholine-modified protein efficiently inhibit ATP-mediated IL-1β release in human and rat monocytes via nicotinic acetylcholine receptors containing subunits α7, α9, and/or α10. Of note, we identify receptors for phosphocholine-modified macromolecules that are synthesized by microbes and eukaryotic parasites and are well-known modulators of the immune system. Our data suggest that an endogenous anti-inflammatory cholinergic control mechanism effectively controls ATP-mediated release of IL-1β and that the same mechanism is used by symbionts and misused by parasites to evade innate immune responses of the host. Copyright © 2015 by The American Association of Immunologists, Inc.
    The Journal of Immunology 07/2015; 195(5). DOI:10.4049/jimmunol.1400974 · 4.92 Impact Factor
  • Pneumologie 07/2015; 69(07). DOI:10.1055/s-0035-1556628
  • Pneumologie 07/2015; 69(07). DOI:10.1055/s-0035-1556629
  • Pneumologie 07/2015; 69(07). DOI:10.1055/s-0035-1556630
  • Pneumologie 07/2015; 69(07). DOI:10.1055/s-0035-1556631
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    ABSTRACT: Hintergrund In mehreren klinischen Studien zeigt sich eine Verbesserung der Langzeitprognose für Patienten, die unter perioperativer periduraler Schmerztherapie zusätzlich zur Allgemeinnarkose an einem kolorektalen Karzinom operiert wurden. Fragestellung Hat eine zusätzlich verwendete perioperative peridurale Analgesie (PDA) einen Effekt auf das Langzeitüberleben von Patienten nach chirurgischer Resektion eines kolorektalen Karzinoms? Material und Methoden Es erfolgten eine systematische Literaturrecherche (bis 5/2014) in Medline sowie eine Metaanalyse des Einflusses einer PDA auf das Langzeitüberleben von Patienten nach Resektion eines kolorektalen Karzinoms in den UICC-Stadien I bis IV. Die korrigierten Hazard Ratios (HR) mit einem 95 %-Konfidenzintervall (KI) wurden als Maß für den statistischen Effekt auf das Langzeitüberleben zugrunde gelegt. Für die Analyse wurde ein Modell mit zufälligen Effekten verwendet und auf einen potenziell publikationsbezogenen Fehler überprüft (Forest-/Funnel-Plot). Ergebnisse Von 608 identifizierten Publikationen wurden 5 Studien eingeschlossen. Im Modell mit zufälligen Effekten zeigte sich ein verbessertes Langzeitüberleben für Patienten, die perioperativ zusätzlich zur Allgemeinnarkose eine PDA erhielten (HR = 0,81, 95 %-KI 0,68–0,97, p = 0,055). Die Analyse der Einflussfaktoren zeigte einen statistisch robusten Effekt. Damit verminderte sich das Sterblichkeitsrisiko in den analysierten Studien durch die Verwendung einer PDA im Mittel um 19 % gegenüber einer alleinigen Allgemeinanästhesie. Diskussion Diese Metaanalyse zeigt trotz eines Publikationsbias, dass eine zusätzliche perioperative peridurale Analgesie das Langzeitüberleben von Patienten mit einem nicht fernmetastisierten kolorektalen Karzinom nach chirurgischer Resektion verbessern kann.
    Der Chirurg 07/2015; 86(7):655-661. DOI:10.1007/s00104-014-2891-y · 0.57 Impact Factor
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    ABSTRACT: To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial. PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications. A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up. From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to-treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters. The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
    Annals of surgery 07/2015; DOI:10.1097/SLA.0000000000001240 · 8.33 Impact Factor
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    ABSTRACT: Acute rejection is a major risk factor for chronic allograft injury (CAI). Blood leukocytes interacting with allograft endothelial cells during acute rejection were suggested to contribute to the still enigmatic pathogenesis of CAI. We hypothesize that tissue transglutaminase (Tgm2), a multifunctional protein and established marker of M2 macrophages, is involved in acute and chronic graft rejection. We focus on leukocytes accumulating in blood vessels of rat renal allografts (Fischer-344 to Lewis), an established model for reversible acute rejection and CAI. Monocytes in graft blood vessels overexpress Tgm2 when acute rejection peaks on day 9 after transplantation. Concomitantly, caspase-3 is activated, suggesting that Tgm2 expression is linked to apoptosis. After resolution of acute rejection on day 42, leukocytic Tgm2 levels are lower and activated caspase-3 does not differ among isografts and allografts. Cystamine was applied for 4 weeks after transplantation to inhibit extracellular transglutaminase activity, which did, however, not reduce CAI in the long run. In conclusion, this is the first report on Tgm2 expression by monocytes in vivo. Tgm2 may be involved in leukocytic apoptosis and thus in reversion of acute rejection. However, our data do not support a role of extracellular transglutaminase activity as a factor triggering CAI during self-limiting acute rejection.
    Mediators of Inflammation 06/2015; 2015:1-13. DOI:10.1155/2015/429653 · 3.24 Impact Factor
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    ABSTRACT: In addition to its well-described role in lipid metabolism, apolipoprotein E (ApoE) exerts immunomodulatory functions. A protective role of ApoE and ApoE-mimetic peptide (ApoE(133-149)) application was documented in several inflammatory disorders. In this study, we test the hypothesis that ApoE(133-149) promotes renal allograft survival. Dark Agouti, Brown Norway, and Fischer 344 kidneys were transplanted to Lewis rats to investigate fatal and reversible acute rejection. Apolipoprotein E expression was assessed in intravascular leukocytes of renal grafts, in graft tissue and in recipient blood plasma. Recipients of Brown Norway kidneys were treated with ApoE(133-149), and graft survival was monitored until day 100. Graft infiltration, cytokine, and chemokine production were analyzed. Intravascular graft leukocytes and renal tissue obtained from animals undergoing reversible acute rejection expressed increased levels of ApoE mRNA, whereas during fatal rejection, ApoE expression was reduced or remained unchanged. Animals treated with ApoE(133-149) showed prolonged allograft survival, which was associated with a reduced infiltration of CD8 and α/β T-cell receptor-expressing cells, diminished Granzyme B mRNA expression, and decreased caspase-3 activation. Endogenous ApoE overexpression and exogenous application of ApoE(133-149) seem to protect renal allografts from fatal acute rejection. This effect was associated with a reduced influx of cytotoxic T cells.
    Transplantation 02/2015; 99(5). DOI:10.1097/TP.0000000000000569 · 3.83 Impact Factor
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    Der Chirurg 01/2015; 86(1):55-55. DOI:10.1007/s00104-014-2906-8 · 0.57 Impact Factor
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    ABSTRACT: Die akute Mesenterialischämie stellt auch heutzutage aufgrund ihrer hohen Letalität den behandelnden Mediziner vor eine große Herausforderung. Unspezifische Symptome in der frühen Phase der Erkrankung erschweren eine rasche Diagnose der Mesenterialischämie und nur eine frühzeitige Diagnose und Therapie kann den Patienten vor irreversibler Darmischämie, ausgedehnten Darmresektionen, Sepsis und Tod bewahren. Im Gegensatz zu beispielsweise Troponin als frühem Marker für die kardiale Ischämie ist ein zuverlässiger Marker für die Mesenterialischämie bisher nicht im klinischen Alltag etabliert. Dieser würde eine Früherkennung der Patienten in der frühen, reversiblen Phase ermöglichen. Diese Übersichtsarbeit fasst die Pathophysiologie, Epidemiologie und klinische Symptomatik der akuten Mesenterialischämie zusammen und soll einen Überblick über mögliche Biomarker, allen voran das Serumlaktat, geben. Nur Serumlaktat wird bisher als Routineparameter zur Diagnostik der mesenterialen Ischämie verwendet.
    Der Chirurg 10/2014; 86(1). DOI:10.1007/s00104-014-2887-7 · 0.57 Impact Factor
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    ABSTRACT: Adrenomedullin-2/intermedin stabilizes the pulmonary microvascular barrier challenged by application of thrombin ex vivo and by experimental ventilation in vivo. Here, we test the hypothesis that adrenomedullin-2/intermedin(8-47) protects mouse lungs from ischemia/reperfusion injury in vivo. C57BL/6 mice were anesthetized, intubated, ventilated, and heparinized. Blood vessels and the main bronchus of the left lung were clamped for 90 min. Thereafter, lungs were reperfused for 120 min. Five min before clamping and before reperfusion, mice obtained intravenous injections of adrenomedullin-2/intermedin(8-47). After reperfusion, mice were sacrificed and bronchoalveolar lavage of the left and the right lung was performed separately. The integrity of the blood-air barrier was investigated by electron microscopy using stereological methods. In response to ischemia/reperfusion injury, intraalveolar leukocytes accumulated in the ischemic lung. Two applications of 10 ng/kg body weight adrenomedullin-2/intermedin(8-47) dramatically reduced leukocyte infiltration to about 15% (p ≤ 0.001). Also the proportion of the subpopulation of neutrophil granulocytes decreased (12% vs 5%, p = 0.013). Electron microscopy revealed a protection of the blood-air barrier by adrenomedullin-2/intermedin(8-47). Adrenomedullin-2/intermedin(8-47) ameliorates early ischemia/reperfusion injury in mouse lungs by protecting the integrity of the blood-air barrier and by potently reducing leukocyte influx into the alveolar space. Adrenomedullin-2/intermedin(8-47) might be of therapeutic interest in lung transplantation and cardiopulmonary bypass. “Take home” message: Adrenomedullin-2/intermedin(8-47) ameliorates ischemia/reperfusion injury in mouse lungs and reduces leukocyte influx.
    Peptides 10/2014; 62. DOI:10.1016/j.peptides.2014.09.022 · 2.62 Impact Factor
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    ABSTRACT: Rectovaginal fistulas (RVF) are rare but represent a challenge for both patients and surgeons. The most common cause of RVF is obstetric trauma, and treatment is based on fistula classification and localization of the fistula in relation to the vagina and rectum. Conventional therapy frequently fails, making surgery the most viable approach for fistula repair. One surgical procedure which offers adequate repair of lower and middle rectovaginal fistulas consists of interposition of a bulbocavernosus fat flap also called modified Martius flap. First described by Heinrich Martius in 1928, this approach has been continuously modified and adjusted over time and is used in the repair of various pelvic floor disorders. Overall success rates reported in the literature of the interposition of a Martius flap as an adjunct procedure in the surgical management of RVF are 65-100 %. We present a detailed description of the operation technique together with a discussion of the use of a dorsal-flapped modified Martius flap in the treatment of RVF.
    Geburtshilfe und Frauenheilkunde 10/2014; 74(10):923-927. DOI:10.1055/s-0034-1383149 · 0.94 Impact Factor
  • Medizinische Klinik - Intensivmedizin und Notfallmedizin 10/2014; 109(7):554. DOI:10.1007/s00063-014-0439-z · 0.56 Impact Factor
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    ABSTRACT: Sowohl für den Notaufnahmearzt als auch den Intensivmediziner stellt der Patient mit einem „akuten Abdomen“ eine besondere Herausforderung dar. Dabei ist der sog. brettharte Bauch Resultat einer sekundären Peritonitis, die zwangsläufig in einer intraabdominellen Sepsis gipfelt. Diese kritisch kranken Patienten profitieren von einer möglichst raschen Diagnostik und interdisziplinären Therapie. Die Gruppe der Patienten mit einer postoperativen Peritonitis (z. B. nach Anastomoseninsuffizienz) weist oftmals ein maskiertes klinisches Bild auf, das ein Grund für die inakzeptabel hohe Letalität ist. Nach Durchlaufen einer Standarddiagnostik wird die Indikation zur Computertomographie früh gestellt, da sie zusätzlich zur Fokussuche bereits eine Operationsplanung und ggf. eine radiologisch-interventionelle Drainageeinlage erlaubt. Die Therapie fußt auf 3 elementaren Säulen: der raschen Fokussanierung, einer breiten Antibiotikatherapie und den supportiven intensivmedizinischen Maßnahmen.
    Medizinische Klinik - Intensivmedizin und Notfallmedizin 09/2014; 109(6). DOI:10.1007/s00063-013-0335-y · 0.56 Impact Factor
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    ABSTRACT: Acute rejection and respiratory infections are major risk factors for chronic lung allograft dysfunction (CLAD) after lung transplantation. To shed light on the enigmatic aetiology of CLAD we test the following hypotheses using a new experimental model: 1) Alloimmune-independent pulmonary inflammation reactivates alloimmunity. 2) Alloimmunity enhances the susceptibility of the graft towards pathogen associated molecular patterns. Pulmonary Fischer 344 to Lewis rat allografts were treated with lipopolysaccharide (LPS), which consistently results in lesions typical for CLAD. Grafts, local lymph nodes, and spleens were harvested before (day 28) and after LPS application (days 29, 33, and 40) for real-time RT-PCR and immunohistochemistry. Mixed lymphocyte reactions were performed on day 33. Four weeks after transplantation, lung allografts displayed mononuclear infiltrates compatible with acute rejection and over-expressed most components of the Toll-like receptor system. Allografts but not secondary lymphoid organs expressed increased levels of Th1-type transcription factors and cytokines. LPS induced macrophage infiltration as well as mRNA expression of pro-inflammatory cytokines and effector molecules of innate immunity. Unexpectedly, T cell reactivity was not enhanced by LPS. We conclude that prevention of CLAD might be accomplished by local suppression of Th1 cells in stable grafts and by controlling innate immunity during alloimmune-independent pulmonary inflammation.This article is protected by copyright. All rights reserved.
    Transplant International 09/2014; 28(1). DOI:10.1111/tri.12444 · 2.60 Impact Factor
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    ABSTRACT: Peptide YY is produced by L cells in the mucosa of the distal ileum, colon, and rectum and may have systemic and paracrine functions. We hypothesized that peptide YY is expressed by peripheral blood mononuclear cells. The purpose of the present study was to evaluate the expression of peptide YY mRNA and peptide by peripheral blood mononuclear cells and differentiated THP-1 cells after lipopolysaccharide treatment as an in vitro model of inflammation. Blood was drawn by venipuncture from 18- to 63-year-old healthy male blood donors (n = 63); peptide YY mRNA expression levels were detected in peripheral blood mononuclear cells from all healthy male subjects. In 3 subjects, peripheral blood mononuclear cells were cultured for 3 and 24 h and peptide YY was detected in the cell culture supernatant. In human monocytic THP-1 cells treated with phorbol-12-myristate-13-acetate to induce differentiation to macrophages, treatment with lipopolysaccharide caused down-regulation of peptide YY mRNA levels. In summary, freshly isolated peripheral blood mononuclear cells from healthy humans expressed peptide YY. In vitro data suggested that peptide YY expression is down-regulated by differentiation of monocytes to macrophages and proinflammatory stimuli.
    Peptides 08/2014; 58. DOI:10.1016/j.peptides.2014.05.009 · 2.62 Impact Factor

Publication Stats

933 Citations
359.48 Total Impact Points


  • 2009–2015
    • Vitos Gießen-Marburg
      Giessen, Hesse, Germany
  • 1991–2015
    • Justus-Liebig-Universität Gießen
      • • Department of Internal Medicine
      • • Department of Pediatric Hematology and Oncology
      • • Department of Anaesthesiology and Intensive Care Medicine
      Giessen, Hesse, Germany
  • 2006–2014
    • Universitätsklinikum Gießen und Marburg
      • Klinik für Allgemein-, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie
      Marburg, Hesse, Germany
  • 1999
    • Universität Heidelberg
      • Department of Transplantation Immunology
      Heidelburg, Baden-Württemberg, Germany
  • 1986–1987
    • Harvard Medical School
      • Department of Surgery
      Boston, Massachusetts, United States