Osteonecrosis of the jaw in a Crohn’s disease patient following a course of Bisphosphonate and Adalimumab therapy: a case report

Background Bisphosphonates have a widespread indication for osteoporosis and are also applied in cancer patients with skeletal-related conditions. Bisphosphonate-associated osteonecrosis of the jaw (BRONJ) is a feared side effect which is hard to treat and often affects patient´s quality of life in an extensive manner. Adalimumab (Humira®), a fully human recombinant antibody specific for tumor necrosis factor- α, is approved for treatment in patients with Inflammatory Bowel Disease like ulcerative colitis or Crohn’s disease. Case presentation In March 2013, a 36-year-old female presented with right-sided perimandibular swelling, recurrent facial pain and exposed necrotic bone after previous extraction of tooth 47. She had the medical history of Crohn’s disease for more than one decade with chronic active enterocolitis, fistula disease as well as previous oral manifestation and was currently treated with Adalimumab since September 2008. Due to steroid-induced osteoporosis, diagnosed in 2004, she received oral Bisphosphonates (Risedronate) from 2004 until 2007 followed by two infusions of Zoledronic acid in 2008 and 2009. Conclusion This patient with a medical history of Crohn’s disease and gastrointestinal remission under Adalimumab therapy presented with osteonecrosis of the jaw after suspended oral and intravenous Bisphosphonate therapy implicating that the biologic therapy with an anti-TNF-α antibody might promote the manifestation of osteonecrosis and compromise oral healing capacity

Imaging foreign bodies in head and neck trauma: a pictorial review

Open injuries bear the risk of foreign body contamination. Commonly encountered materials include gravel debris, glass fragments, wooden splinters or metal particles. While foreign body incorporation is obvious in some injury patterns, other injuries may not display hints of being contaminated with foreign body materials. Foreign objects that have not been detected and removed bear the risk of leading to severe wound infections and chronic wound healing disorders. Besides these severe health issues, medicolegal consequences should be considered. While an accurate clinical examination is the first step for the detection of foreign body materials, choosing the appropriate radiological imaging is decisive for the detection or non-detection of the foreign material. Especially in cases of impaired wound healing over time, the existence of an undetected foreign object needs to be considered. Here, we would like to give a practical radiological guide for the assessment of foreign objects in head and neck injuries by a special selection of patients with different injury patterns and various foreign body materials with regard to the present literature

Einfluss von pharmakologischer Parasympathikusstimulation und alloplastischer Fremdkörperimplantation auf die Immunantwort in der murinen polymikrobiellen Sepsis

Mit dem cholinergen antiinflammatorischen Signalweg (CAP) konnte in den letzten Jahren eine vielversprechende Therapieoption identifiziert werden, um die unverändert hohe Letalität der klinischen Sepsis entscheidend zu senken. Die Untersuchung des therapeutischen Nutzens einer pharmakologischen Parasympathikusstimulation in der murinen polymikrobiellen Sepsis der Colon Ascendens Stent Peritonitis (CASP) war eine Hauptfragestellung dieser Arbeit. Untersucht wurden die Auswirkungen von Nikotin auf das Überleben und die Zytokinspiegel in der CASP. Es konnte gezeigt werden, dass die Effektstärke des CAP im Vollbild der polymikrobiellen Sepsis ihre Limitation erfährt. Hierdurch wurde die Hypothese gefestigt, dass eine Stimulation des CAP vornehmlich in Hyperinflammationsmodellen protektiv wirkt, aber keine oder sogar eine nachteilige Wirkung in Sepsismodellen mit wesentlicher Infektionskomponente besitzt. Der CAP wirkt folglich antiinflammatorisch, aber nicht antiinfektiös. Chirurgische Eingriffe besitzen eine immunmodulierende Wirkung. Kleine chirurgische Eingriffe können immunaktivierend wirken, größere Operationen hingegen das Immunsystem paralysieren. Diese beiden diametralen Verläufe könnten einen entscheidenden Einfluss auf das Outcome einer postoperativen Sepsis haben. Ein regelrecht konditioniertes Immunsystem könnte eine Schutzwirkung entfalten und die Sepsismorbidität und -mortalität senken. Diese Arbeit hat gezeigt, dass kleinere, sterile periphere Eingriffe eine Art „operative Impfwirkung“ besitzen. Erkenntnisse über die Reaktions- und Regulationsmechanismen nähren die Hoffnung, durch geeignete Anpassung des operativen Behandlungsregimes eine immunologische Alteration herbeiführen zu können und so den Ausgang großer chirurgischer Eingriffe in Zukunft entscheidend verbessern zu können.The discovery of the cholinergic anti-inflammatory pathway (CAP) has generated hopes for a new potential treatment in clinical sepsis. Here, the therapeutic stimulation of the CAP by nicotine was analysed in Colon Ascendens Stent Peritonitis (CASP), a murine model for severe sepsis. In CASP no major benefitial effects were observed in respect to survival and cytokine levels. These findings suggest that the CAP has limited effects in severe sepsis. Positive effects of cholinergic receptor stimulation might be limited to dampening the detrimental results of hyperinflammation rather than being effective in infection. Surgery itself exerts immunomodulating effects. Minor surgical procedures might stimulate the immune system while extended surgery can cause immunoparalysis. Both phenomena might have great influence on the outcome of postoperative sepsis. Well-dosed immunostimulation could exert protective effects. It was shown that a minor surgical trauma, e.g. the subcutaneous implantation of an osmotic pump, leads to highly elevated survival rates and primed splenocytes, measured by ex vivo cytokine release of TNF-a, if performed 3 days prior to the onset of sepsis. Implementation of these observations into perioperative management protocols might have great clinical impact on postoperative sepsis

Die Rolle der Leber im cholinergen antiinflammatorischen Signalweg unter besonderer Betrachtung der Kupffer-Zellen

Der „cholinerge antiinflammatorische Signalweg“ beschreibt einen vagalen, neuroimmunologischen Reflexmechanismus, der einen hemmenden Einfluss auf Immunzellen des Retikuloendothelialen Systems in lokalen und generalisierten Entzündungsgeschehen ausübt. Vermittelt wird dieser Reflexmechanismus über den α7-Subtyp des nikotinischen Acetylcholinrezeptors auf Makrophagen. Die in der Leber lokalisierten Kupffer-Zellen repräsentieren ca. 80 – 90% der Gewebsmakrophagen des Körpers. Während die neuroimmunologische Regulation von Peritoneal- und Alveolarmakrophagen sowie Monozyten durch den N. vagus gut dokumentiert ist, ist die Rolle der Kupffer-Zellen im „cholinergen antiinflammatorischen Signalweg“ noch unbekannt. In der vorliegenden Arbeit wurde der parasympathische Einfluss auf die residente Makrophagenpopulation der Leber, die Kupffer-Zellen, untersucht. Nikotin als Agonist am α7nAChR zeigte in vitro im LPS-Modell keine Alteration der Zytokinantwort von Kupffer-Zellen aus nativen C57Bl/6-Mäusen. Hingegen führte die subdiaphragmale Vagotomie zu einer Reduktion der in vitro TNF-α-Antwort von Kupffer-Zellen nach Stimulation mit LPS. Die Daten dieser Arbeit erweitern den Wissensstand über die neuroimmunologische Interaktion zwischen Parasympathikus und den residenten Makrophagenpopulationen des Körpers. In Analogie zur sympathischen Regulation des Immunsystems, das abhängig vom angesprochenen Rezeptortyp sowohl pro- als auch antiinflammatorisch wirken kann, deuten die Ergebnisse der vorliegenden Arbeit zu murinen Kupffer-Zellen darauf hin, dass auch der Parasympathikus, neben seinen bekannten antiinflammatorischen Eigenschaften, kompartimentalisiert ebenfalls proinflammatorisch wirken könnte.The cholinergic anti-inflammatory pathway represents a neuro-immunological reflex that exerts an inhibitory effect on immune cells in local and generalised inflammation. This pathway is mediated via the α7-subtype of nicotinic acetylcholine receptors on macrophages. Kupffer cells in the liver account for 80 – 90 % of all tissue macrophages. The neuro-immunological control of peritoneal and alveolar macrophages by the vagal nerve is well-documented. However, little is known about the interplay of the cholinergic anti-inflammatory pathway and Kupffer cells. This study investigated the vagal influence on Kupffer cells. Nicotine, an agonist of the α7-subtype nicotinic acetylcholine receptor, didn't alter the in vitro LPS-induced cytokine release of Kupffer cells from C57Bl/6 mice. However, complete subdiaphragmatic vagotomy lead to lower levels of LPS-induced TNF-α in supernatants of murine Kupffer cells. This study provides novel evidence of a neuro-immunological interaction between the vagal nerve and the resident macrophages of the liver. In contrast to peritoneal and alveolar macrophages however, these findings suggest a pro-inflammatory effect of the vagal nerve on Kupffer cells

Patient-Specific 3D-Printed Miniplates for Free Flap Fixation at the Mandible: A Feasibility Study

Background: This study was conducted to evaluate the feasibility, clinical outcomes, and accuracy of patient-specific 3D-printed miniplates for mandible reconstruction with fibula free flaps. Methods: A feasibility study was conducted with 8 patients. Following virtual planning, patient-specific 1.0 mm titanium non-locking miniplates were produced via laser selective melting. 3D-printed cutting and drilling guides were used for segmental mandible resection and flap harvesting. Flap fixation was performed with two 4-hole miniplates and 2.0 mm non-locking screws (screw length 7 mm) for each intersegmental gap. Clinical follow-up was at least 6 months. Preoperative and postoperative CT/cone beam CT data were used for 3D accuracy analysis and evaluation of bone healing. Plate-related complications were monitored clinically. Results: Patient-specific miniplate fixation of all flaps was successfully conducted (4 mono-segmental, 4 dual-segmental) with high accuracy (3.64 ± 1.18 mm) between the virtual plan and postoperative result. No technical complications were encountered intraoperatively. Osseous union occurred in all intersegmental gaps (1 partial, 18 complete) after 10 ± 2 months. No material fracture, dislocation, or plate exposure was observed. Conclusions: Based on this pilot observational study including a limited number of patients, free flap fixation for mandibular reconstruction with patient-specific 3D-printed miniplates is feasible and associated with high accuracy, bone healing, and remote soft tissue complications

Impact of Dental Implant Surface Modifications on Osseointegration

Objective. The aim of this paper is to review different surface modifications of dental implants and their effect on osseointegration. Common marketed as well as experimental surface modifications are discussed. Discussion. The major challenge for contemporary dental implantologists is to provide oral rehabilitation to patients with healthy bone conditions asking for rapid loading protocols or to patients with quantitatively or qualitatively compromised bone. These charging conditions require advances in implant surface design. The elucidation of bone healing physiology has driven investigators to engineer implant surfaces that closely mimic natural bone characteristics. This paper provides a comprehensive overview of surface modifications that beneficially alter the topography, hydrophilicity, and outer coating of dental implants in order to enhance osseointegration in healthy as well as in compromised bone. In the first part, this paper discusses dental implants that have been successfully used for a number of years focusing on sandblasting, acid-etching, and hydrophilic surface textures. Hereafter, new techniques like Discrete Crystalline Deposition, laser ablation, and surface coatings with proteins, drugs, or growth factors are presented. Conclusion. Major advancements have been made in developing novel surfaces of dental implants. These innovations set the stage for rehabilitating patients with high success and predictable survival rates even in challenging conditions

The Role of the Vagus Nerve: Modulation of the Inflammatory Reaction in Murine Polymicrobial Sepsis

The particular importance of the vagus nerve for the pathophysiology of peritonitis becomes more and more apparent. In this work we provide evidence for the vagal modulation of inflammation in the murine model of colon ascendens stent peritonitis (CASP). Vagotomy significantly increases mortality in polymicrobial sepsis. This effect is not accounted for by the dilatation of gastric volume following vagotomy. As the stimulation of cholinergic receptors by nicotine has no therapeutic effect, the lack of nicotine is also not the reason for the reduced survival rate. In fact, increased septic mortality is a consequence of the absent modulating influence of the vagus nerve on the immune system: we detected significantly elevated serum corticosterone levels in vagotomised mice 24 h following CASP and a decreased ex vivo TNF-alpha secretion of Kupffer cells upon stimulation with LPS. In conclusion, the vagus nerve has a modulating influence in polymicrobial sepsis by attenuating the immune dysregulation