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Purpose Pyrotechnics are a long-standing tradition at the turn of the year. There are little data available on New Year's Eve-associated ORL injuries. Due to restrictions during the Corona pandemic, the handling of fireworks and meetings on New Year's Eve 2020–2022 had been significantly changed. Our aim was to analyze first data about New Year's Eve-associated ORL injuries. Methods A retrospective analysis of 16 turns of the year (2006–2022) at a University ORL department was performed. The 2 recent years were influenced by the changes and restrictions of the COVID-19 pandemic. Results Of 343 emergency presentations, 69 presented with New Year's Eve-associated reasons (20%). 72% were male, 15.9% were underage. 74% presented for fireworks-related injuries, 19% due to violent altercations. Noise trauma was present in 71%. The average number of New Year's Eve-associated emergency patients per year and the average total number of patients were reduced by more than half under COVID-19 pandemic conditions. Conclusions New Year's Eve-associated ORL injuries range from inner ear trauma to midface fractures. Long-term damage may include hearing loss and tinnitus. These results shall support the responsible use of fireworks even after the end of the special regulations of the COVID-19 pandemic.

Einleitung Seit Mai 2020 wurden die ersten POC Tests für die SARS-CoV-2 Diagnostik angeboten, welche mit der Notwendigkeit des nasopharyngealen Abstrichs verbunden waren. Aufgrund des langen Arbeitskanals durch die Nasenhaupthöhle besteht das Risiko einer Schleimhautverletzung mit konsekutiver Epistaxis. Methodik Wir beschreiben den Krankheitsverlauf zweier Patientinnen, bei denen es nach extern durchgeführtem nasopharyngealen Test zu einer massiven interventionspflichtigen Epistaxis nasi kam. Ergebnisse Bei einer Patientin musste nach frustraner Nasentamponade eine endonasale Blutstillung in Intubationsnarkose durchgeführt werden. Bei einer zweiten Patientin kam es zu einer Hb-relevanten Epistaxis nasi mit hämorrhagischem Schock. Sie wurde intubiert und beatmet stationär übernommen. Schlussfolgerung Der transnasale Test in der SARS-CoV-2 Diagnostik führt in seltenen Fällen zu lebensbedrohlichen Komplikationen. Aufgrund der weltweit über 5 Millionen täglich durchgeführten Tests im Rahmen der aktuellen Pandemie sind Komplikationen nicht zu vernachlässigen. Es ist unverzichtbar, dass die den Abstrich durchführende Person die Anatomie detailliert kennt. Alternative Testmethoden werden bezüglich ihrer Sensitivität weiter beurteilt. Hinsichtlich der auch zukünftig bestehenden Notwendigkeit von SARS-CoV-2-Tests ist eine weitere Etablierung alternativer und risikoärmerer Testverfahren unerlässlich.

ACE inhibitor (ACEi) induced angioedema predominantly affects the upper aerodigestive tract. As ACEi induced angioedema is mediated by bradykinin, therapeutic response to antihistamines and glucocorticoids remains unsatisfactory. In bradykinin mediated hereditary angioedema, C1-esterase inhibitor (C1INH) is an effective and approved treatment since many years. Our aim was to evaluate the therapeutic effect of C1INH in ACEi induced angioedema.We performed a double-blind, parallel-group, multicentre randomised placebo-controlled trial between December 2013 and September 2018. Eligible were adults with ACEi induced angioedema with airway obstruction. Participants were randomised 1:1 to single doses of either C1INH (20 IU/kg) or placebo (0.9% NaCl) i.v in addition to standard care (i.v. 500 mg prednisolone and 2.68 mg clemastine) i.v. Composite symptom scores were assessed at baseline and up to 48 h, at discharge and 1 week after discharge. Physician assessed time to complete oedema resolution (TCER) and time to onset of relief (TOR).30 patients (16 C1INH, 14 placebo) were randomised and dosed. 25 (9 C1INH, 12 placebo) completed the study. TCER was 29.63 h ± 15.56 h in the C1INH and 17.29 h ± 10.40 h in the placebo arm (p = 0.0457). TORs were 4.13 h ± 3.38 h and 2.86 h ± 1.29 h for C1INH and placebo, respectively (p = 0.4443). There were no adverse events related to study medication.In the context of baseline application of steroids and antihistamines C1INH was inferior in the treatment of ACEi induced angioedema when compared to placebo with respect to time to complete resolution of symptoms. Eudra-CT Number: 2012-001670-28.

OBJECTIVES There are three surgical treatment options for patients with peritonsillar abscess (PTA): needle aspiration, incision and drainage (ID), and abscess tonsillectomy (ATE). The updated German national guideline (2015) included changes in the treatment of PTA. The indication for tonsillectomy (TE) in patients became more stringent and preference was given to ID in certain cases. STUDY DESIGN Retrospective analysis. METHODS We performed a retrospective systematic analysis of patient data using the in-house electronic patient records and considered a 4-year period from 2014 to 2017. About 584 patients were identified. Our aim was to analyze the influence of the updated guideline on clinical practice. RESULTS 236 of 584 patients (40.4%) underwent ATE with contralateral TE. In 225 patients (38.5%), unilateral ATE was performed. Mean surgery time was significantly shortened when only unilateral ATE was performed. Concerning postoperative bleeding, we noted a tendency toward a lower incidence after ATE in comparison to ATE with contralateral TE. Less than 1% of patients who underwent ATE had to be revised surgically due to postoperative hemorrhage. After the revision of the guideline, unilateral ATE and ID were conducted more frequently. CONCLUSION These results support that ATE in an inpatient setting is a considerably safe and effective primary therapeutic option. ID represents a favorable treatment option for patients with PTA and comorbidities, nevertheless, patient compliance is required and insufficient drainage or recurrence of PTA may occur. The revision of the guideline had a significant impact on the choice of interventions (P

One of the main symptoms of severe infection with the new coronavirus‑2 (SARS-CoV-2) is hypoxemic respiratory failure because of viral pneumonia with the need for mechanical ventilation. Prolonged mechanical ventilation may require a tracheostomy, but the increased risk for contamination is a matter of considerable debate.Evaluation of safety and effects of surgical tracheostomy on ventilation parameters and outcome in patients with COVID-19.Retrospective observational study between March 27 and May 18, 2020, in a single-center coronavirus disease-designated ICU at a tertiary care German hospital.Patients with COVID-19 were treated with open surgical tracheostomy due to severe hypoxemic respiratory failure requiring mechanical ventilation.Clinical and ventilation data were obtained from medical records in a retrospective manner.A total of 18 patients with confirmed SARS-CoV‑2 infection and surgical tracheostomy were analyzed. The age range was 42-87 years. All patients received open tracheostomy between 2-16 days after admission. Ventilation after tracheostomy was less invasive (reduction in PEAK and positive end-expiratory pressure [PEEP]) and lung compliance increased over time after tracheostomy. Also, sedative drugs could be reduced, and patients had a reduced need of norepinephrine to maintain hemodynamic stability. Six of 18 patients died. All surgical staff were equipped with N99-masks and facial shields or with powered air-purifying respirators (PAPR).Our data suggest that open surgical tracheostomy can be performed without severe complications in patients with COVID-19. Tracheostomy may reduce invasiveness of mechanical ventilation and the need for sedative drugs and norepinehprine. Recommendations for personal protective equipment (PPE) for surgical staff should be followed when PPE is available to avoid contamination of the personnel.HINTERGRUND: Ein Hauptsymptom der schweren Infektion mit dem neuen Coronavirus‑2 (SARS-CoV-2) ist das hypoxämische Atemversagen aufgrund einer Viruspneumonie, welches eine mechanische Beatmung erfordert. Eine längere mechanische Beatmung erfordert ggf. eine Tracheostomie, welche aufgrund des erhöhten Kontaminationsrisikos jedoch umstritten ist. ZIEL: Bewertung von Sicherheit und Auswirkungen der chirurgischen Tracheostomie auf Beatmungsparameter und Überleben bei Patienten mit COVID-19.Retrospektive Beobachtungsstudie zwischen 27. März und 18. Mai 2020 auf einer COVID-Intensivstation in einem Krankenhaus der Tertiärversorgung.Patienten mit COVID-19 wurden wegen schweren hypoxämischen Atemversagens mit offener chirurgischer Tracheostomie behandelt.Klinische Daten und Beatmungsparameter wurden retrospektiv aus medizinischen Unterlagen entnommen.Analysiert wurden die Daten von 18 Patienten mit chirurgischer Tracheostomie bei bestätigter SARS-CoV-2-Infektion. Die Altersspanne betrug 42–87 Jahre. Bei allen Patienten erfolgte zwischen 2 und 16 Tage nach der Aufnahme eine offene Tracheostomie. Anschließend war die Beatmung weniger invasiv, die Lungen-Compliance nahm zu und die Sedierung konnte reduziert werden. Es starben 6 von 18 Patienten. Alle chirurgischen Mitarbeiter waren mit FFP3-Masken oder mit motorbetriebenen luftreinigenden Atemschutzmasken ausgestattet.Die vorliegenden Daten legen nahe, dass eine offene chirurgische Tracheostomie ohne schwerwiegende Komplikationen durchgeführt werden kann. Diese kann die Invasivität der mechanischen Beatmung sowie den Bedarf an Beruhigungsmitteln und Katecholaminen verringern. Falls verfügbar, sollten Empfehlungen für die persönliche Schutzausrüstung befolgt werden.

Dimension, position and stability of the cartilaginous nasal septum are crucial for successful surgery of the nasal septum. The objective of septoplasty is to create sufficient space in the anterior parts of the nose, particularly in the region of the nasal valves. Therefore, the cartilaginous nasal septum should obtain a state of "balanced tension". Essential steps of septoplasty include the hemitransfixion incision, the dissection of subperichondrial/subperiosteal tunnels, the mobilization via chondrotomy/osteotomy, the resection of cartilage/bone, the replantation of extracorporeally straightened material/reconstruction of the caudal nasal septum, closure by suture and fixation with nasal splints. Firmness of the caudal nasal septum is essential for sustainable septal surgery. It ensures the stability of the entire cartilaginous nose over decades.

Radikale Kieferhohlenoperationen galten bis in die 1990er-Jahre als Standardeingriff bei Erkrankungen der Kieferhohle, werden aber aufgrund der hohen Morbiditat nicht mehr favorisiert. Die „functional endoscopic sinus surgery“ (FESS) gilt heute als Goldstandard der Nebenhohlenchirurgie. Modifikationen der Zugangswege ermoglichen heute auch Zugange zu bisher schwierig erreichbaren Regionen der Kieferhohle. Je nach Anatomie und pathologischer Veranderung konnen unterschiedliche Arten der Erweiterung des Kieferhohlenostiums gewahlt werden. Bei der Sinusotomie Typ I wird das naturliche Ostium um maximal 1 cm nach dorsal erweitert. Die Sinusotomie Typ II beinhaltet eine Erweiterung des naturlichen Ostiums bis zu einem maximalen Durchmesser von 2 cm. Bei der Sinusotomie Typ III erfolgt eine Erweiterung des Ostiums nach dorsal bis zur Hinterwand des Sinus maxillaris und nach kaudal bis zum Ansatz der unteren Muschel. Als invasivere Zugange stehen neben dem pralakrimalen Zugang die mediale Maxillektomie, bei der die mediale Wand der Kieferhohle reseziert wird, und deren Modifikationen „mega antrostomy“ und „extended maxillary antrostomy“ zur Verfugung. Die richtige Wahl der Grose des Kieferhohlenfensters ist die Grundvoraussetzung fur eine erfolgreiche Therapie und fur den langfristigen postoperativen Erfolg. Isolierte purulente sinusitische Beschwerden der Kieferhohle konnen i. d. R. durch defensive Erweiterungen des Ostiums (Typ I) therapiert werden. Die Sinusotomie Typ II wird bei Polyposis nasi mit Beteiligung der Mukosa des Ostiums, rezidivierender Stenose nach Voroperation, chronischer Sinusitis maxillaris aufgrund zystischer Fibrose, eitriger Sinusitis maxillaris mit Beteiligung benachbarter Nebenhohlen eingesetzt. Eine Sinusotomie Typ III ist erforderlich bei Choanalpolypen mit Ansatz am Boden der Kieferhohle, ausgedehnter Polyposis und Pilzsinusitis sowie bei invertiertem Papillom. Vor allem bei (Rezidiv‑)Erkrankungen und ausgedehnten Interventionen in der Kieferhohle konnen die mediale Maxillektomie und deren Modifikationen erforderlich werden.

Introduction Nonsteroidal anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (NERD) is defined by intolerance to cyclooxygenase 1 inhibitors, chronic rhinosinusitis with recurrent nasal polyps, and/or intrinsic bronchial asthma. Long-term administration of acetylsalicylic acid (ASA) after desensitization has been used to mitigate these sequelae, but the optimal dose and balancing symptom relief and side effects remain unsettled. Methods Retrospective data analysis of 85 patients with NERD receiving maintenance therapy of 300 mg ASA was followed by questionnaires (our own, not validated and the Sino-Nasal Outcome Test-20). We received responses from 55 patients and examined 30 of them clinically. Results Patients with no ASA-associated side effects were 56.4% (56 of 85 patients) of the cohort. In this study, 60% (33 of 55 patients) continued prophylaxis of 300 mg ASA daily for an average of 34.7 months. Elective surgery was the most frequent cause of discontinuation of ASA (21.8%; 12 of 55 patients). Rhinomanometry values were significantly improved with ASA ( P Conclusions Minor clinical improvements were identified. Side effects were well tolerated by most patients, and no serious sequelae occurred. The indications for long-term ASA therapy in NERD patients remain unsettled.

Since May 2020, the first nasopharyngeal POC tests for SARS-CoV-2 diagnostic have been available. Due to the long passage through the nasal cavity, there is a risk of injury with subsequent epistaxis.We describe the course of disease of two female patients who suffered from massive epistaxis requiring intervention after an externally performed nasopharyngeal swab.After nasal tamponade, one patient underwent clipping of the sphenopalatine artery under general anesthesia. The other patient suffered from nasal bleeding with hemorrhagic shock requiring transfusion. She was intubated and admitted to our hospital.The nasopharyngeal swab for diagnosis of SARS-CoV-2 can lead to life-threatening complications in rare cases. Considering that daily more than 5 million corona tests are being carried out worldwide as part of the current pandemic, complications should not be neglected. It is necessary that the person performing the swab has a detailed understanding of the anatomy involved. Alternative test methods were further assessed with regard to their sensitivity. With regard to the future need for SARS-CoV-2 tests, alternative and lower-risk test procedures must be investigated and established.Seit Mai 2020 wurden die ersten POC Tests für die SARS-CoV-2 Diagnostik angeboten, welche mit der Notwendigkeit des nasopharyngealen Abstrichs verbunden waren. Aufgrund des langen Arbeitskanals durch die Nasenhaupthöhle besteht das Risiko einer Schleimhautverletzung mit konsekutiver Epistaxis.Wir beschreiben den Krankheitsverlauf zweier Patientinnen, bei denen es nach extern durchgeführtem nasopharyngealen Test zu einer massiven interventionspflichtigen Epistaxis nasi kam.Bei einer Patientin musste nach frustraner Nasentamponade eine endonasale Blutstillung in Intubationsnarkose durchgeführt werden. Bei einer zweiten Patientin kam es zu einer Hb-relevanten Epistaxis nasi mit hämorrhagischem Schock. Sie wurde intubiert und beatmet stationär übernommen.Der transnasale Test in der SARS-CoV-2 Diagnostik führt in seltenen Fällen zu lebensbedrohlichen Komplikationen. Aufgrund der weltweit über 5 Millionen täglich durchgeführten Tests im Rahmen der aktuellen Pandemie sind Komplikationen nicht zu vernachlässigen. Es ist unverzichtbar, dass die den Abstrich durchführende Person die Anatomie detailliert kennt. Alternative Testmethoden werden bezüglich ihrer Sensitivität weiter beurteilt. Hinsichtlich der auch zukünftig bestehenden Notwendigkeit von SARS-CoV-2-Tests ist eine weitere Etablierung alternativer und risikoärmerer Testverfahren unerlässlich.

Physiologische Alterungsprozesse des Immunsystems gehen mit einer erhohten Anfalligkeit fur Infektionskrankheiten, Autoimmun- und Tumorerkrankungen einher. Entsprechend der allgemeinen demographischen Entwicklung steigt auch die Anzahl der Tumorpatienten mit fortgeschrittenem Lebensalter zunehmend. Ein Ende dieser Entwicklung ist bislang nicht absehbar. Bei der Tumorbehandlung gewinnt die Immuntherapie mit Checkpoint-Inhibitoren stetig an Bedeutung, allerdings existieren bislang nur wenige Studien zu Wirksamkeit und Nebenwirkungsprofil bei alteren Patienten. In dieser Ubersichtsarbeit werden die Veranderungen des Immunsystems im Alter und ihr Einfluss auf die Karzinogenese erortert. Daruber hinaus wird auf den aktuellen Forschungsstand zur Immuntherapie von Patienten im fortgeschrittenen Lebensalter mit einem Kopf-Hals-Tumor eingegangen.

Objective Less than 5% of deep vein thrombosis is due to thrombosis of the internal jugular vein. Genetic, malignant or inflammatory underlying diseases as well as insertion of venous catheters can be responsible for this pathology. Due to its rare occurrence, it is difficult to find systematic research about thrombosis of the internal jugular vein. Methods We performed a systematic analysis of present patient data from our ENT department with the electronic patient record considering the period from 2012-2017. Search terms were “thrombosis” and “jugular internal vein”. We identified 41 patients with the requested diagnosis and performed further analysis of the cases. Internal jugular vein thrombosis was diagnosed in all patients using Duplex sonography and/or CT/MR angiography. Results Paraneoplastic thrombosis was found in 22/41 patients (54%), in 15 of the 22 (68%), the tumor was located in the ENT region. Two out of seven (29%) of the patients with tumor entities outside the head and neck region had thrombosis of the internal jugular vein as the first symptom of the disease. Another 14/41 patients (34%) had underlying inflammatory diseases – mostly streptococci-associated – for example a cervical abscess. In two patients, insertion of a central-venous catheter was causal, in three patients we could not find any reason for the development of thrombosis. Conclusion To diagnose the rare and often asymptomatic thrombosis of the internal jugular vein, ultrasound of the cervical region should always include vascular imaging. Thrombosis of the internal jugular vein results mostly paraneoplastic or due to inflammation/abscess. It can be the first symptom of a malignant primary disease and always requires detailed diagnostic clarification. Level of evidence 4.

Aims: Angioedema is a rare side effect of angiotensin-converting enzyme (ACE) inhibitors. It remains unclear why it is only induced in a few patients taking ACE inhibitors, often after a long period of uneventful treatment. The aim of this study was to analyze the influence of ACE inhibitor treatment on C1-inhibitor (C1-INH) levels. Methods: Captopril (5 mg/25 mg) was added to blood samples of 5 healthy subjects. C1-INH levels were measured before and after incubation for 180 min. The second section of the study was done with 17 patients who received therapy with an ACE inhibitor for the first time. C1-INH levels were measured before ACE inhibitor treatment, 24 h after first drug administration, and 4 weeks later. Results: After incubation of blood samples with 5 mg captopril, there was no detectable change in C1-INH levels. After incubation with 25 mg, C1-INH activity was decreased by an average of 29% and the C1-INH concentration was decreased by an average of 0.06 g/L. In the second study section, inconsistent effects on C1-INH levels were detected. In the majority of patients, 24 h after the first ACE inhibitor administration C1-INH activity was tending to be increased. Conclusions: A dose-dependent effect on C1-INH levels in captopril-incubated blood samples of healthy test persons was shown. In patients with new ACE inhibitor treatment, heterogeneous reactions of C1-INH values were detected. Larger studies are needed over a longer period of time to find correlations between the effect of ACE inhibitor therapy on C1-INH levels and the clinical course/development of side effects.

Introduction: Hereditary angioedema (HAE) is a disease that leads to recurrent swelling of the skin and mucous membranes, including the upper airway tract. Apart from being deadly, these attacks can be debilitating, which leads to a poor quality of life in patients. Clinicians are occasionally confronted with patients who have recurrent attacks despite treatment with C1 esterase inhibitor concentrate or β2-receptor antagonists. The goal of this study was to investigate repeated attacks that occur 48 hours to 7 days (“cluster attacks”) after treatment, to determine why they occur and the factors that may be associated with them, and thus to prevent their occurrence. Methods: We conducted a multicenter mixed retrospective-prospective study with data acquired from all documented attacks in our patients with collective (n = 132) between 2015 and 2018. Results: Eighty-five percent (n = 132) of our total patient collective (N = 156) agreed to participate in the study. Nine percent of these patients (n = 12) had cluster attacks, with a total of 48 cluster attacks. The data procured from the patients were mixed retrospective‐prospective. Approximately 72% of all the cluster attacks were caused by exogenous stimuli (41% due to psychological stress, 29% due to physical stimuli, and 2% due to menstruation). Cluster attacks occurred in 7% of the patients who received prophylactic therapy in comparison with 12.5% of patients who received on-demand therapy. Cluster attacks comprised 48.4% of all the attacks that patients with cluster-attacks (n= 9) experienced. In addition, the patients who were underdosing their C1 esterase inhibitor treatment had cluster attacks more often. A lower “time to repeated attack” was seen in the patients who received on-demand therapy compared with those who received prophylactic therapy. Discussion: The percentage of the patients who had attacks as a result of exogenous triggers was higher in the cluster-attack group (70.5%) compared with the general HAE population (30‐42%). Repeated attacks, therefore, were strongly associated with external triggers. The patients who received prophylactic treatment and who experienced cluster attacks were highly likely to have been underdosing, which may explain the repeated attacks despite treatment. In the patients prone to cluster attacks, prophylaxis should be considered.

Background and objectives Patients with the rare disease hereditary angioedema (HAE) suffer from recurrent acute attacks of edema. There is no curative therapy, but the frequency of attacks and quality of life of severely affected patients can be improved by prophylactic therapy. The monoclonal antibody lanadelumab has been approved for routine prophylaxis in patients with HAE since November 2018. Patients and methods In this prospective assessment, a long-term therapy with lanadelumab was initiated in 12 adult patients with HAE. We analyzed their course of disease 6 months after the start of long-term prophylactic therapy using a validated quality-of-life questionnaire and evaluated the frequency and severity of attacks as well as side effects. Furthermore, the therapy with lanadelumab was compared with the previous medication. Results To date, our study is the first prospective quality of life analysis in HAE patients under treatment with lanadelumab in real life conditions. Mean attack frequencies were reduced from 6.4 to 0.3 attacks per month and patient in our cohort (Pl0.0001). No severe attacks occurred under lanadelumab prophylaxis. In all patients, quality of life increased significantly. Conclusions Lanadelumab is an effective but expensive long-term prophylaxis for HAE patients. A favorable side-effect profile has been shown. J Drugs Dermatol. 2020;19(10):978-983. doi:10.36849/JDD.2020.5269.

Dimension, position and stability of the cartilaginous nasal septum are crucial for successful surgery of the nasal septum. The objective of septoplasty is to create sufficient space in the anterior parts of the nose, particularly in the region of the nasal valves. Therefore, the cartilaginous nasal septum should obtain a state of "balanced tension". Essential steps of septoplasty include the hemitransfixion incision, the dissection of subperichondrial/subperiosteal tunnels, the mobilization via chondrotomy/osteotomy, the resection of cartilage/bone, the replantation of extracorporeally straightened material/reconstruction of the caudal nasal septum, closure by suture and fixation with nasal splints. Firmness of the caudal nasal septum is essential for sustainable septal surgery. It ensures the stability of the entire cartilaginous nose over decades.

Background Hereditary angioedema (HAE) is a rare genetic disorder that leads to recurrent development of mucosal and dermal swelling. It is mediated by bradykinin, and can affect virtually any part of the human body, including the gastrointestinal tract, the extremities, and the laryngeal and pharyngeal regions. Safe and potent drugs are available for acute and prophylactic treatment of HAE. Owing to its unspecific symptoms and unique manifestations, HAE is often misdiagnosed and treated incorrectly. Abdominal edema in particular can resemble appendicitis or cholecystitis, and is therefore often treated with unnecessary surgical procedures. We performed a questionnaire study to quantify this issue. Patients and methods We designed questionnaires for HAE patients and probands without HAE. The patient-control ratio was chosen at 1 : 2. Results Compared with the general population, HAE patients are subject to a significantly greater number of invasive diagnostic and therapeutic interventions. Our study showed that the HAE patients were 2.5 times more likely to undergo abdominal surgery (including gynecological and urological procedures) than the individuals without HAE (p = 0.007). The number of operations per patient correlated with the period (number of years) between the onset of symptoms and diagnosis (correlation coefficient 0.511; Spearman). Furthermore, twice as many appendectomies were performed on HAE patients (18.9 % vs. 37.7 %). Our results also showed that the HAE patients were 2.3 times more likely to undergo a gastroscopy than the control group without HAE (p = 0.003). Conclusions Patients with rare diseases such as HAE not only suffer from the effects of the disease itself. The conditions are often misdiagnosed for years owing to the general lack of knowledge about such diseases and unspecific manifestations. This leads not only to erroneous and ineffective treatment, but also to needless invasive diagnostic and therapeutic medical procedures. It is therefore important to increase the general knowledge and awareness of orphan diseases such as HAE with a view to improving diagnosis and treatment, minimizing the patients' suffering and enhancing their quality of life.

Bradykininvermittelte durch Medikamenteneinnahme induzierte Schwellungen wie das durch einen Angiotensin Converting Enzym-Inhibitor induzierte (ACEi) Angioodem (AE) treten fast ausschlieslich im Bereich der oberen Schluck-Atem-Strase auf und sind somit potenziell lebensbedrohlich. Bislang gibt es fur diese Krankheitsentitat weder eine Leitlinie noch eine zugelassene medikamentose Therapieform. Die ublicherweise verabreichten Kortisonderivate und Antihistaminika zeigen sich annahernd wirkungslos. Erstellung eines Algorithmus als mogliches Leitschema zur Notfallversorgung und Akuttherapie der medikamenteninduzierten, bradykininvermittelten Angioodeme. Es erfolgte eine retrospektive Analyse aller Patienten mit akutem Angioodem an der Klinik fur Hals‑, Nasen- und Ohrenheilkunde, Kopf- und Halschirurgie des Universitatsklinikums Ulm, in der Therapie und Verlauf akuter Schwellungen untersucht wurden. Weiterhin erfolgte eine PubMed-Literaturrecherche mit den Suchwortern „acute angioedema“, „angioedema emergency“, „ACE angioedema“, „bradykinin angioedema“ und „angioedema therapy“. Eine weitere Basis stellten die aktuellen Leitlinien zum hereditaren Angioodem, der Therapie der Anaphylaxie sowie anasthesiologische Leitlinien des Atemwegsmanagements dar. Ein Notfallalgorithmus im Sinne eines Ablaufdiagramms wurde erstellt. Schwerpunkte sind dabei die Kriterien „Entscheidung zur Atemwegssicherung/Intubation“ und die medikamentose Therapie: Antihistaminika und Glukokortikoide versus Antibradykinintherapie. Ein weiterer Aspekt lag in Empfehlungen zur detaillierten Durchfuhrung der stationaren Patientenuberwachung. Bislang ist die Therapie der medikamenteninduzierten, bradykininvermittelten Angioodeme nur „off-label“ und ohne Leitliniengrundlage moglich. Der dargestellte Notfallalgorithmus stellt einen ersten strukturierten Ansatzpunkt fur die Akutversorgung betroffener Patienten dar.

Sustained interest and an increase of possible indications endorse the role of robot-assisted surgery of the head and neck region. However, broad clinical application is impeded by substantial extra cost, time exposure and a supposed deficit of haptic and tactile feedback. The role of haptic feedback has barely been examined in this context, and literature provides only limited objective validation. This point of criticism applies to all commercially available systems. We created an experimental setup to evaluate, quantify and compare the performance of surgical systems. The daVinci system (Intuitive Surgical), the Flex system (Medrobotics) and standard rigid instruments (23 cm laryngoscopic grasper, Karl Storz) were compared with the human hand by head and neck surgeons (n = 15), performing a variety of surgical tasks. Specific samples with different rigidity were sorted with all devices, and the resulting orders were analyzed by permutation analysis, indicating differences in precision and accuracy of haptic and tactile feedback. The human hand was superior in all trials, acting as reference modality. The flexible instruments of the Flex system performed better than the electro-mechanically decoupled instruments of the daVinci system for the majority of measures recorded, suggesting a benefit in terms of haptic and tactile feedback in this context. While not all aspects of haptic and tactile feedback were accessible, this first objective comparison endorses the inferiority of robot-assisted surgery in terms of haptic and tactile feedback, compared to the human sense or standard surgical tools. Furthermore, the immediate force transmission of the Flex system seems to be superior to the electro-mechanical transformation of the daVinci system, indicating an advantage in terms of haptic and tactile feedback in immediate comparison. This study is providing a basis for further experiments and the development of robotic surgery towards an implementation in clinical routine.

Background: Non-allergic angioedema is largely driven by increased plasma levels of bradykinin and over-activation of bradykinin receptor type II (B2), but the specific downstream signalling pathways remain unclear. The aim of this study was to identify signal transduction events involved in bradykinin-induced dermal extravasation. Methods: Quantification of dermal extravasation was accomplished following intradermal (i.d.) injection of bradykinin or the B2 agonist labradimil in mice with endothelial NO-synthase (eNOS) deficiency and in C57BL/6J mice pre-treated with vehicle, NO-synthase or cyclooxygenase (COX) inhibitors. In the multicentre clinical study ABRASE, 38 healthy volunteers received i.d. bradykinin injections into the ventral forearm before and after oral treatment with the COX inhibitor ibuprofen (600 mg). The primary endpoint of ABRASE was the mean time to complete resolution of wheals (TTCR) and the secondary endpoint was the change of maximal wheal size. Results: Neither NOS inhibitors nor eNOS deficiency altered bradykinin-induced extravasation. In striking contrast, the COX inhibitors ibuprofen, diclofenac, SC560 and celecoxib significantly diminished this extravasation when given before injection. As for diclofenac, a similar but significantly lower effect was observed when given after i.d. injection of bradykinin. Similar results were obtained when bradykinin was replaced by labradimil. In volunteers, ibuprofen significantly reduced TTCR (P

Background: Hereditary angioedema (HAE) patients suffer from recurrent swellings. Current standard therapy consists of C1 esterase inhibitor (C1-INH) and bradykinin receptor B2 antagonists. Severe courses require prophylactic treatment. For such patients, it has been demonstrated that the intravenous (IV) administration of C1-INH [C1-INH(IV)] is safe and effective. A new prophylactic option is subcutaneous (SC) treatment with C1-INH. Methods and Case: We present the case of an HAE patient placed on prophylactic C1-INH(IV) therapy due to frequent attacks when managed with on-demand therapy. An implanted port allowed the periodical and safe application of medication until the device was explanted due to an infection. Due to the poor venous access, repeated IV application failed. Therefore, we began a SC treatment with 1500 IU C1-INH [C1-INH(SC)] as long-term prophylaxis and analyzed the clinical course over 16 months. Results: Under the SC prophylaxis, the number of attacks were reduced to 1/month in comparison to 4.33/month with no prophylactic treatment and 1.83/month with C1-INH(IV). No severe attacks and no attack within the upper airway occurred over the 16 months of C1-INH(SC) treatment. As a result, quality of life improved, as measured by the Angioedema quality of life questionaire (AE-QoL). Conclusion: Self-administered SC prophylactic use of C1-INH over a period of 16 months seems to be a well tolerated and efficient. The patient’s quality of life improved, and by learning self-application, the patient gained independence., publishedVersion

Tailor-made poly(α-methylstyrene)- and poly(4-methylstyrene)-block-poly(4-vinylpyridine) diblock copolymers with poly(4-vinylpyridine) as the minority component were synthesised via living anionic polymerisation. In bulk they show spherical or cylindrical microphases. From these block copolymers highly-ordered isoporous block copolymer membranes were prepared by combining block copolymer selfassembly and the nonsolvent induced phase separation process (SNIPS). The membrane properties were analysed by water flux and retention measurements. Due to the high glass transition temperatures of the major blocks these block copolymer membranes show a thermal stability up to 150 °C.

Objective Determine the effect of bradykinin on solute permeability and cellular junctional proteins in human dermis microvascular endothelial cells. Methods Cells were characterized by immunofluorescence and fluorescence���activated cell sorting. Macromolecular transport of dextran and albumin was monitored. Junctional protein expression and phosphorylation were determined by immunoblot analyses. Intracellular calcium and cAMP levels were evaluated. Target gene expression at mRNA and protein levels was determined. Results Human dermis microvascular endothelial cells comprised 97% lymphatic endothelial cells. Bradykinin increased the permeability to dextran in a concentration���dependent manner, while reduced the permeability to albumin. Bradykinin treatment down���regulated VE���cadherin expression and affected its phosphorylation status at Tyr731. It also down���regulated claudin���5 expression at the transcriptional level through bradykinin���2���receptor signaling. An increase in the intracellular calcium levels and a reduction in the cAMP concentration were associated effects. Finally, bradykinin induced the up���regulation of vascular endothelial growth factor���C protein which was found increased in BK���induced human dermis microvascular endothelial cells culture supernates. Conclusions Human dermis microvascular endothelial cells represent a model of lymphatic endothelial cells, in which bradykinin���2���receptor is expressed. Bradykinin���induced bradykinin���2���receptor signaling through intracellular calcium mobilization and reduction in cAMP levels, triggered changes in solute permeability and cellular junction expression. It further up���regulated vascular endothelial growth factors���C protein expression, which is a key modulator of lymphatic vessels function and lymphangiogenesis, publishedVersion

BACKGROUND Patients suffering from bradykinin-induced angioedema show recurrent swelling of subcutaneous and submucosal structures. Increased bradykinin levels lead to an increase in vascular permeability and edema formation. Current therapy consists of B2 bradykinin receptor antagonists, C1-esterase-inhibitor (C1-INH) concentrate, or the kallikrein inhibitor ecallantide. In most cases the treatment of acute attacks is sufficient. Prophylactic therapy is recommended only in severe cases. C1-INHc has been shown a safe and efficient option. Its effect on the quality of life has not yet been analyzed. STUDY DESIGN AND METHODS Patients with inadequate disease control despite an “on-demand therapy” including C1-INHc and/or the B2 receptor antagonist icatibant were switched to long-term prophylaxis consisting in an individual dose of intravenous C1-INHc (Cinryze). None of the patients had been previously treated with ecallantide. Disease-specific quality-of-life questionnaires and patient records were used for evaluation. Disease control, quality of life, adverse events, and administered dosage per month were compared for 6 months on on-demand therapy and the following 6 months under prophylactic therapy. RESULTS Data of seven patients with hereditary angioedema (HAE) and one patient with acquired angioedema were evaluated. Prophylactic therapy with Cinryze led to a significant and clinically relevant reduction in the overall attack frequency from 6.7 to 2.3 per month without relevant side effects. The frequency of severe attacks was reduced by 89% and quality of life significantly improved. CONCLUSION Prophylaxis with Cinryze led to a significantly improved quality of life in our cohort of patients with high-frequency bradykinin-induced angioedema attacks that were not sufficiently treated with on-demand medication.

This performance study deals with isoporous ultrafiltration membranes made through a combination of self-assembly of amphiphilic block copolymers and the non-solvent induced phase separation process (SNIPS). Ten different polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) diblock copolymers were used to prepare membranes with pore sizes increasing with the molecular weight of the polymers. The pore diameters of the membranes vary from 17 to 86 nm. Pure water permeances were studied with respect to pore sizes, P4VP content, thickness of the membranes and flux recovery after protein adsorption. Suitable working conditions were identified and rejection of poly(ethylene glycol) (PEG) molecules with molecular weights between 100 and 1000 kDa were carried out. The characteristics of PS-b-P4VP diblock copolymer membranes were compared with a commercially available polyethersulfone ultrafiltration membrane.

The combination of the self-assembly of amphiphilic block copolymers and the nonsolvent induced phase inversion process offers an efficient way to isoporous integral-asymmetric membranes. In this context we report fast, easily upscalable and material reducing ways to thin self-assembled membranes. Therefore, we succeeded to implement a spray or dip coating step into the membrane formation process of different diblock copolymers like polystyrene-block-poly(4-vinylpyridine), poly(α-methylstyrene)-bock-poly(4-vinylpyridine), and polystyrene-block-poly(iso-propylglycidyl methacrylate). The formation of hexagonal pore structures was possible using a highly diluted one solvent system allowing the reduction of diblock copolymer consumption and therefore the production costs are minimized compared to conventional blade casting approaches. The broad applicability of the process was proven by using different flat and hollow fiber support materials. Furthermore, the membranes made by this new method showed a more than 6-fold increase in water flux compared to conventional polystyrene-block-poly(4-vinylpyridine) membranes with similar pore sizes prepared by blade casting. The membranes could be proven to be stable at transmembrane pressures of 2 bar and showed a pH responsive flux behavior over several cycles.

Patient: Female, 83 Final Diagnosis: Angioedema Symptoms: Edema Medication: Ramipril Clinical Procedure: — Specialty: Otolaryngology Objective: Unusual clinical course Background: Bradykinin is an underestimated mediator of angioedema. One subgroup of bradykinin induced angioedema is angioedema triggered by treatment with angiotensin converting enzyme (ACE) inhibitors. Due to its localization in the head and neck region and its unpredictable course, it is a possibly life-threatening condition. There is not an officially approved treatment for ACE inhibitor induced angioedema. Case Report: We present a case of an 83-year-old woman, who presented to our ENT department because of acute swelling of the tongue. On admission, there was no pharyngeal or laryngeal edema and no dyspnea. Treatment with glucocorticoids and antihistamines had no response. The patient had ramipril as regular medication, so we assumed ACE inhibitor induced angioedema and treated consequently with C1-inhibitor (human) 1,500 IU. Nevertheless, swelling was progressive and required intubation. Even after the second specific treatment with icatibant, her angioedema subsided extremely slowly. The patient also had regular treatment with saxagliptin, a dipeptidyl peptidase 4 inhibitor, so we assumed that the simultaneous inhibition of two bradykinin degrading enzymes led to a treatment-refractory course of angioedema. Conclusions: General awareness for bradykinin induced angioedema due to regular medication is limited. Our case demonstrated the importance of improving awareness and knowledge about this side effect. We need a better understanding of the pathomechanism to aid in more precise clinical diagnosis. Securing the patient’s airway as well as administration of an officially approved therapy is of utmost importance. As the number of patients simultaneously treated with antihypertensive and antidiabetic drugs is likely to increase, the incidence of bradykinin mediated drug induced angioedema is likely to increase as well.

Membrane formation via the combination of self-assembly and the non-solvent induced phase separation (NIPS) process of diblock copolymers is investigated. Several polystyrene- block -poly(4-vinylpyridine) (PS- b -P4VP) diblock copolymers with different molecular weights and weight percentages of both blocks are tested under different parameters, leading to membrane surfaces with uniform pores of approximately 20–70 nm diameter. The average pore diameter is proved to be adjustable by changing the total molar mass of the block copolymer. The solution composition is an additional parameter controlling the structure formation. The purpose was to explore the upper and lower limits of the membrane structure formation by varying the molecular weight and the composition of the block copolymer. Scanning electron microscopy (SEM) is used to image the surface morphology and the homogeneity of the pore sizes. Primary results of water flux and retention are presented.