Management von medikamentenassoziierten Kiefernekrosen – Ergebnisse einer Literaturanalyse neuester Studien im Vergleich zu bewährten Strategien

BACKGROUND Antiresorptive agents are some of the most frequently used drugs worldwide, with indications in osteology and oncology. They are generally well tolerated and display a~favorable safety profile. A~potentially severe unwanted side effect is medication-related osteonecrosis of the jaw (MRONJ). PURPOSE OF THIS REVIEW This review summarizes the latest developments in etiology, diagnosis, and treatment of MRONJ, and compares new insights with established algorithms. METHODS A~systematic review of relevant studies exploring diagnostic methods, prospective management trials, and innovative studies on the pathogenesis of MRONJ published between 2016 and 2021 was performed. The study quality was assessed using the MINORS (methodological index for non-randomized studies) rating score. RESULTS AND DISCUSSION The prevalence of MRONJ in patients undergoing treatment with antiresorptive drugs for oncological reasons is remarkable (2-12%). MRONJ prevalence in patients receiving antiresorptive drugs for the treatment of osteoporosis is much lower (0.1-1%). MRONJ treatment should be initiated early and involve a~surgical approach. MRONJ treatment is safe and predictable, with long-term success rates of more than 85%. ZUSAMMENFASSUNG HINTERGRUND: Antiresorptiva gehören weltweit zu den am häufigsten applizierten Arzneimitteln. Ihr Haupteinsatzbereich liegt in der Osteologie und Onkologie. Trotz allgemein guter Verträglichkeit treten bei Patienten unter Therapie unerwünschte Arzneimittelwirkungen (UAW) auf. Eine spezifische UAW im Bereich der Kiefer ist die sog. medikamentenassoziierte Osteonekrose („medication-related osteonecrosis of the jaw“, MRONJ) der Kiefer. ZIEL DER ARBEIT Diese Arbeit stellt neuesten Entwicklungen in Ätiologie, Diagnostik und Therapie der MRONJ im Vergleich zu bereits bestehenden Erkenntnissen zusammen. METHODIK Es wurde eine systematische Literaturübersicht der Jahre 2016–2021 zu diesem Thema durchgeführt. Prospektive Therapiestudien, Diagnostikstudien mit Vergleichsgruppe und innovative Studien zur Pathogenese der MRONJ wurden eingeschlossen und nach den MINORS-Kriterien („methodological index for non-randomized studies“) bewertet. ERGEBNISSE UND DISKUSSION Die MRONJ tritt bei ca.~2–12 % der Patienten, die aus onkologischer Indikation mit Antiresorptiva behandelt werden, auf (osteologische Indikation ca.~0,1–1 %). Die Therapie der MRONJ sollte frühzeitig und operativ erfolgen. Die Heilungsrate ist bei einem operativen Therapieansatz mit über 85 % sehr gut

Deep neck infections: A single-center analysis of 63 cases

Background and Purpose: With the use of antibiotic therapy, the incidence of deep neck infections has decreased in recent decades. The aim of this investigation was to review the clinical course and the management of deep neck infections in our department, compare them to the experiences of the common literature and identify predisposing factors for lethal complications. Material and Methods: In this single-center analysis, 63 patients with deep neck infections were treated surgically. The following clinical data were analyzed and compared: age, gender, laboratory data, spatial manifestation, therapeutic modalities, comorbidities, length of hospitalization and complications. Results: There was a predominance of male patients (58.7%) and a mean age of 57.9 years. The most common symptoms at diagnosis were sore throat (96.8%) and neck swelling (92.0%). Cardio/pulmonary diseases and diabetes mellitus were the most common comorbidities. There was a significantly longer hospital stay for patients with diabetes mellitus. The most common manifestation was a parapharyngeal abscess in 24 patients (38.1%), followed by peri-/retrotonsillar infections in 19 patients (30.2%). In 29 patients, a multiple space infection was observed, with a significantly longer duration of hospitalization and a higher rate of complications. The main life-threatening complication was the development of airway obstruction in 20 patients (31.7%), who all received a tracheostomy. The duration of hospitalization for patients with complications was significantly longer. Conclusions: Close attention must be paid to the management of patients with deep neck infections, especially patients with diabetes mellitus and cardio/pulmonary diseases or patients with multiple space infections. Key words:Deep neck infections, comorbidities, surgical treatment, tracheostomy, diabetes mellitus

Inhibition of stimulated meningeal blood flow by a calcitonin gene-related peptide binding mirror-image RNA oligonucleotide

1. Calcitonin gene-related peptide (CGRP) released from trigeminal afferents is known to play an important role in the control of intracranial blood flow. In a rat preparation with exposed cranial dura mater, periods of electrical stimulation induce increases in meningeal blood flow. These responses are due to arterial vasodilatation mediated in part by the release of CGRP. In this preparation, the effect of a CGRP-binding mirror-image oligonucleotide (Spiegelmer NOX-C89) was examined. 2. Spiegelmer NOX-C89 applied topically at concentrations between 10(−7)and 10(−5) M to the exposed dura mater led to a dose-dependent inhibition of the electrically evoked blood flow increases. The highest dose reduced the mean increases in flow to 56% of the respective control levels. A nonfunctional control Spiegelmer (not binding to CGRP) was ineffective in changing blood flow increases. Intravenous injection of NOX-C89 (5 mg kg(−1)) reduced the evoked blood flow increases to an average of 65.5% of the control. The basal blood flow was not changed by any of the applied substances. 3. In addition, an ex vivo preparation of the hemisected rat skull was used to determine CGRP release from the cranial dura mater caused by antidromic activation of meningeal afferents. In this model, 10(−6) M of NOX-C89 reduced the evoked CGRP release by about 50%. 4. We conclude that increases in meningeal blood flow due to afferent activation can be reduced by sequestering the released CGRP and thus preventing it from activating vascular CGRP receptors. Moreover, the Spiegelmer NOX-C89 may inhibit CGRP release from meningeal afferents. Therefore, the approach to interfere with the CGRP/CGRP receptor system by binding the CGRP may open a new opportunity for the therapy of diseases that are linked to excessive CGRP release such as some forms of primary headaches