Establishment of the deuterium oxide dilution method as a new possibility for determining the transendothelial water permeability.

Increase in transendothelial water permeability is an essential etiological factor in a variety of diseases like edema and shock. Despite the high clinical relevance, there has been no precise method to detect transendothelial water flow until now. The deuterium oxide (D2O) dilution method, already established for measuring transepithelial water transport, was used to precisely determine the transendothelial water permeability. It detected appropriate transendothelial water flow induced by different hydrostatic forces. This was shown in four different endothelial cell types. The general experimental setup was verified by gravimetry and absorbance spectroscopy. Determination of transendothelial electrical resistance (TEER) and immunocytochemical staining for proteins of the cell-cell contacts were performed to ensure that no damage to the endothelium occurred because of the measurements. Furthermore, endothelial barrier function was modulated. Measurement of transendothelial water flux was verified by measuring the TEER, the apparent permeability coefficient and the electrical capacity. The barrier-promoting substances cyclic adenosine monophosphate and iloprost reduced TEER and electrical capacity and increased permeability. This was accompanied by a reduced transendothelial water flux. In contrast, the barrier-damaging substances thrombin, histamine and bradykinin reduced TEER and electrical capacity, but increased permeability. Here, an increased water flow was shown. This newly established in vitro method for direct measurement of transendothelial water permeability was verified as a highly precise technique in various assays. The use of patient-specific endothelial cells enables individualized precision medicine in the context of basic edema research, for example regarding the development of barrier-protective pharmaceuticals.

Acquired Angioedema Due to C1-Inhibitor Deficiency (AAE-C1-INH)-A Bicenter Retrospective Study on Diagnosis, Course, and Therapy.

BACKGROUND: Acquired angioedema with C1-inhibitor deficiency (AAE-C1-INH) is a rare condition resembling hereditary angioedema (HAE), but with late onset and low C1-inhibitor (C1-INH) due to consumption potentially caused by autoimmune diseases and mainly lymphatic malignancies. Being about 10-fold rarer than HAE, there is limited knowledge and no licensed therapy. OBJECTIVE: To report clinical and biological data from a newly described population of 20 patients with AAE-C1-INH assessing diagnostic delay, AAE-C1-INH:HAE-ratio, underlying conditions, and therapeutic management in Germany. METHODS: Retrospective data analysis of 20 patients from 2 angioedema centers in southern Germany. RESULTS: Median age at symptoms' onset was 64 years (60% females), with predominant swellings of the face (85%) and low levels for C1-INH in almost all patients. The ratio AAE-C1-INH:HAE was 1:9.7. From symptoms' onset to diagnosis of AAE-C1-INH, the median delay was 7.5 months, and between AAE-C1-INH symptoms' onset and diagnosis of the underlying hematological condition (n = 9) it was 4 months (median). Four patients had a history of solid neoplasm, 1 had a papillary thyroid carcinoma as the only potential cause for AAE-C1-INH, with treatment of the malignancy resulting in resolution of AAE-C1-INH. All the symptomatic patients were treated with off-label on-demand icatibant subcutaneously or C1-INH concentrate intravenously, and 6 severely affected patients needed off-label long-term prophylaxis with good symptom control. CONCLUSIONS: AAE-C1-INH is characterized by late-onset swellings mainly involving the face and low C1-INH levels. Diagnostic delay for AAE-C1-INH is further decreasing despite being about 10-fold rarer than HAE. Patients severely affected without underlying condition or no indication for treatment could benefit from off-label therapy.

New Year's Eve in otorhinolaryngology: a 16-year retrospective evaluation.

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.

[Functional disorders of the nose - definition, diagnostics and treatment options]. / Funktionelle Formstörungen der Nase ­ Definition, Diagnostik und Therapieoptionen.

The surgical spectrum of functional rhinosurgery includes nasal septum surgery, septorhinoplasty and nasal concha surgery. Based on the German guideline "Disorders of the inner and/or external nose (with functional and/or aesthetic impairment)" published in April 2022, which was prepared on behalf of the German Society of Otorhinolaryngology, Head and Neck Surgery, we discuss the indications, diagnostic approaches, the planning of the surgery and postoperative care. The most common findings of the external nose with a functional impairment include crooked nose, saddle nose, and tension nose. Combined pathologies occur. Well-documented in-depth consultation is essential for rhinosurgical procedures. In the case of revision surgery, the possible necessity of autologous ear or rib cartilage should be considered. Despite correct surgical performance, no "guarantee" can be given for the surgical (long-term) result in rhinosurgery.

The Surgical Treatment of Peritonsillar Abscess: A Retrospective Analysis in 584 Patients.

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 < .001), which is reflected by the increased number of unilateral ATE. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2706-2712, 2021.

Surgical tracheostomy in a cohort of COVID-19 patients.

BACKGROUND: One of the main symptoms of severe infection with the new coronavirus­2 (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. OBJECTIVE: Evaluation of safety and effects of surgical tracheostomy on ventilation parameters and outcome in patients with COVID-19. STUDY DESIGN: 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: Patients with COVID-19 were treated with open surgical tracheostomy due to severe hypoxemic respiratory failure requiring mechanical ventilation. MEASUREMENTS: Clinical and ventilation data were obtained from medical records in a retrospective manner. RESULTS: A total of 18 patients with confirmed SARS-CoV­2 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). CONCLUSION: 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.

[Surgery of the Nasal Septum]. / Chirurgie des Nasenseptums.

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.

Symptom Control of Patients With Chronic Rhinosinusitis With Nasal Polyps Under Maintenance Therapy With Daily Acetylsalicylic Acid.

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 < .05; Wilcoxon), but there was no significant reduction in nasal polyposis or improvement in olfaction at the time of follow-up examination. 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.

Thrombosis of the internal jugular vein in the ENT-department - Prevalence, causes and therapy: A retrospective analysis.

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.

Unnecessary abdominal interventions in patients with hereditary angioedema.

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.

Nanofiltrated C1-esterase-inhibitor in the prophylactic treatment of bradykinin-mediated angioedema.

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.