Efficacy of human C1 esterase inhibitor concentrate for treatment of ACE-inhibitor induced angioedema.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

The role of elective neck dissection in T1 and T2 nasal cavity squamous cell carcinomas.

PURPOSE: To evaluate the role of elective neck dissection (END) on oncological outcome in early-stage nasal cavity squamous cell carcinomas (SCCs). METHODS: In total, 87 patients with T1 (n = 59; 67.8%) and T2 (n = 28; 32.2%) SCCs were evaluated regarding performance of END, regional recurrences (RR) and its impact on cancer-specific survival (CSS). We further created a risk score based on T-classification, tumor subsite and grading to identify patients whom may benefit from END and calculated the corresponding numbers needed to treat (NNT) to prevent RR. RESULTS: Nine (10.3%) patients experienced RR of whom 3 (5.1%) were T1 and 6 (21.4%) T2 tumors (p = 0.042). All RR originated from moderately or poorly differentiated (G2-G3) SCCs of the nasal septum or vestibule. END was done in 15 (17.2%) patients and none of those experienced RR (p = 0.121). Onset of RR represented the worst prognostic factor for CSS (HR 23.3; p = 0.007) with a 5y-CSS of 44.4% vs. 97.3% (p < 0.001). RR occurred in none of the patients with no or low risk scores compared to 31.6% (6/19) in patients with high-risk scores (p = 0.006). Accordingly, three high-risk patients would need to undergo END (NNT 2.63) to prevent RR compared to a NNT of 8 for the whole cohort. CONCLUSIONS: Although rare, occurrence of RR significantly deteriorates outcome in early stage nasal cavity SCCs, which could be effectively reduced by performance of END. The importance of END is currently underestimated and our proposed risk score helps identifying those patients who will benefit from END.

A randomized trial of icatibant in ACE-inhibitor-induced angioedema.

BACKGROUND: Angioedema induced by treatment with angiotensin-converting-enzyme (ACE) inhibitors accounts for one third of angioedema cases in the emergency room; it is usually manifested in the upper airway and the head and neck region. There is no approved treatment for this potentially life-threatening condition. METHODS: In this multicenter, double-blind, double-dummy, randomized phase 2 study, we assigned patients who had ACE-inhibitor-induced angioedema of the upper aerodigestive tract to treatment with 30 mg of subcutaneous icatibant, a selective bradykinin B2 receptor antagonist, or to the current off-label standard therapy consisting of intravenous prednisolone (500 mg) plus clemastine (2 mg). The primary efficacy end point was the median time to complete resolution of edema. RESULTS: All 27 patients in the per-protocol population had complete resolution of edema. The median time to complete resolution was 8.0 hours (interquartile range, 3.0 to 16.0) with icatibant as compared with 27.1 hours (interquartile range, 20.3 to 48.0) with standard therapy (P=0.002). Three patients receiving standard therapy required rescue intervention with icatibant and prednisolone; 1 patient required tracheotomy. Significantly more patients in the icatibant group than in the standard-therapy group had complete resolution of edema within 4 hours after treatment (5 of 13 vs. 0 of 14, P=0.02). The median time to the onset of symptom relief (according to a composite investigator-assessed symptom score) was significantly shorter with icatibant than with standard therapy (2.0 hours vs. 11.7 hours, P=0.03). The results were similar when patient-assessed symptom scores were used. CONCLUSIONS: Among patients with ACE-inhibitor-induced angioedema, the time to complete resolution of edema was significantly shorter with icatibant than with combination therapy with a glucocorticoid and an antihistamine. (Funded by Shire and the Federal Ministry of Education and Research of Germany; ClinicalTrials.gov number, NCT01154361.).

A 2-Year Follow-up Study of an Absorbable Implant to Treat Nasal Valve Collapse.

The safety and effectiveness of an absorbable implant for lateral cartilage support have been recently demonstrated in subjects with nasal valve collapse (NVC) at 12 months postprocedure. This follow-up study aimed to assess whether the safety and effectiveness of the implant persist in these patients for 24 months after the procedure. Thirty subjects with Nasal Obstruction Symptom Evaluation (NOSE) score ≥ 55 and isolated NVC were treated; 14 cases were performed in an operating suite under general anesthesia and 16 cases were performed in a clinic-based setting under local anesthesia. The implant, a polylactic acid copolymer, was placed with a delivery tool within the nasal wall to provide lateral cartilage support. Subjects were followed up through 24 months postprocedure. Fifty-six implants were placed in 30 subjects. The mean preoperative NOSE score was 76.7 ± 14.8, with a range of 55 to 100. At 24 months, the mean score was 32.0 ± 29.3, reflecting an average within-patient reduction of -44.0 ± 31.1 points. There were no device-related adverse events in the 12 to 24 months period. There were five subjects who exited the study prior to the 24-month follow-up. Four of the five subjects who exited were elected for further intervention and one subject was lost to follow-up. This study demonstrates safety of an absorbable implant for lateral nasal wall support and symptom improvement in some subjects with NVC at 24 months postprocedure.

Intracranial and intradural nasal polyposis after iatrogenic skull base defect: A case report.

We report the first case of an intracranial and intradural nasal polyposis occurring in a close topographical relation to a previous, iatrogenic anterior skull base defect. The tumour was resected and the skull base defect was closed transnasally by an interdisciplinary team. The histopathological report confirmed recurrent polyposis.

Absorbable Implant to Treat Nasal Valve Collapse.

Objective To evaluate the safety and effectiveness of an absorbable implant for lateral cartilage support in subjects with nasal valve collapse (NVC) with 12 months follow-up. Methods Thirty subjects with Nasal Obstruction Symptom Evaluation (NOSE) score ≥ 55 and isolated NVC were treated; 14 cases were performed in an operating suite under general anesthesia and 16 cases were performed in a clinic-based setting under local anesthesia. The implant, a polylactic acid copolymer, was placed with a delivery tool within the nasal wall to provide lateral cartilage support. Subjects were followed up through 12 months postprocedure. Results Fifty-six implants were placed in 30 subjects. The mean preoperative NOSE score was 76.7 ± 14.8, with a range of 55 to 100. At 12 months, the mean score was 35.2 ± 29.2, reflecting an average within-patient reduction of -40.9 ± 31.2 points. The majority (76%) of the subjects were responders defined as having at least one NOSE class improvement or a NOSE score reduction of at least 20%. There were no adverse changes in cosmetic appearance at 12 months postprocedure. Three implants in three subjects required retrieval within 30 days postprocedure and resulted in no clinical sequelae. Conclusion This study demonstrates safety and effectiveness of an absorbable implant for lateral cartilage support in subjects with NVC at 12 months postprocedure.

Bystander cricothyrotomy with ballpoint pen: a fresh cadaveric feasibility study.

OBJECTIVE: In motion pictures and anecdotal reports, ballpoint pens have been used for life-saving cricothyroidotomies. The objective of this study was to examine the widespread belief that ballpoint pens can perforate the skin and cricothyroid ligament and could be used as substitute tracheostomy sets in an emergency setting. METHODS: Three different ballpoint pens were examined regarding their inner diameter, their demountability to form a cannula and their airflow properties. Ten medical laypersons were asked to try to puncture the trachea through the skin and the cricothyroid ligament in 10 fresh cadavers just using the ballpoint pens. RESULTS: Two of three pens had inner diameters of >3 mm and were both suitable as cannulas in a tracheotomy. All participants could perforate the skin with both ballpoint pens. However, almost no one could penetrate through the cricothyroid ligament or the ventral wall of the trachea, except for one participant. He performed the tracheostomy after three attempts in >5 min with a lot of patience and force. CONCLUSIONS: A cricothyroidotomy just with a ballpoint pen is virtually impossible. First, the airflow resistance in commercially available ballpoint pens is too high to produce effective ventilation. Second, the cricothyroid ligament is too strong to be penetrated by ballpoint pens.

Intraindividual comparison of 1,470 nm diode laser versus carbon dioxide laser for tonsillotomy: a prospective, randomized, double blind, controlled feasibility trial.

INTRODUCTION: The need for reduction of post-tonsillectomy hemorrhage has led to promotion of tonsillotomy techniques for tonsil tissue reduction in obstructive tonsillar hypertrophy. This trial compares ablative tissue effects using 1,470 nm diode laser and carbon dioxide laser for tonsillotomy in an intraindividual design. METHODS: 21 children aged 3-13 years (mean age 6.3 years) underwent laser tonsillotomy for obstructive tonsillar hypertrophy in this double blind, prospective, randomized, clinical feasibility trial. In each of the blinded patients, tonsillotomy was performed using fiber guided 1,470 nm diode laser (contact mode, 15 W power) on the one side and carbon dioxide laser (12 W power) on the other side. An independent, blinded physician documented clinical presentation and patients' symptoms preoperatively and on Days 1, 3, 7, 14, and 21 post-operatively using standardized questionnaire including VAS for each side separately. RESULTS: The mean duration of operative treatment was 2.7 min using 1,470 nm laser and 4.9 min using carbon dioxide laser respectively. Intraoperative bleeding and the frequency of bipolar forceps use for intraoperative bleeding control was significantly less using 1,470 nm diode laser system. There was no difference in post-operative pain scores between the carbon dioxide laser treated and the 1,470 nm fiber guided diode laser treated side. No infections, hemorrhages or other complications occurred in the course of the 3 weeks post-operative period. CONCLUSIONS: A fiber-guided 1,470 nm diode laser system offers an efficient and safe method for tonsillotomy as treatment of obstructive tonsillar hypertrophy. Compared to our standard practice (carbon dioxide laser), 1,470 nm laser application provides comparable tissue ablation effects with less intraoperative bleeding and shorter operation time.

1-year follow-up after radiofrequency tonsillotomy and laser tonsillotomy in children: a prospective, double-blind, clinical study.

In the last decade, tonsillotomy has come into vogue again, whereas the number of tonsillectomies is decreasing rapidly. In a previous study, the tonsillotomy with laser or radiofrequency therapy proved as a safe and effective procedure with minimal pain and hemorrhage. This follow-up study determines which method is more effective with respect to long-term outcome, recurrence of tonsillar hyperplasia and recurrence of tonsillitis. A prospective, randomised, double-blinded controlled clinical study was conducted at the Department of Otorhinolaryngology of the Ludwig-Maximilians-University, Munich, Germany. Twenty-six children with tonsillar hypertrophy were included. Tonsillotomy was performed on one side with monopolar radiofrequency and on the other side with a carbon dioxide laser. Exactly 1 year after the procedure, all 26 patients were documented by digital photography to define a possible recurrence of tonsillar hyperplasia. All parents were asked for occurring tonsillitis and fulfilled the Glasgow Children's Benefit Inventory (GCBI) for health-related quality of life after surgical procedures. In seven children, a slightly visible recurrence of the tonsillar hyperplasia occurred, without any symptoms or correlation to the different methods and sides. One child with recurrent tonsillitis and hyperplasia had to be tonsillectomized 8 months after the initial tonsillotomy procedure. The specimen showed open crypts with bacterial infection in the deep. The GCBI resulted in highly significant benefits of the surgery in all categories and subcategories. In conclusion, both methods, the laser tonsillotomy and the radiofrequency method, were equal concerning the effectiveness and safety after 1 year. Further investigations have to aim at the long-term outcome after tonsillotomy in patients with recurrent infections.

Functional endoscopic surgery of paranasal fungus ball: clinical outcome, patient benefit and health-related quality of life.

Paranasal fungus ball can cause chronic rhinosinusitis. Removal via functional endoscopic sinus surgery is usually performed; however objective data on the overall benefit and patient satisfaction are very scarce. The study focuses on the clinical outcome and the quality of life following endoscopic surgery due to fungus ball sinusitis. Forty patients diagnosed with fungus ball sinusitis who underwent functional endoscopic surgery were included. Epidemiologic data, pre-, intra- and postoperative findings were recorded. Surgical success, the detailed benefit and the health-related quality of life were objectively assessed 1 year after the surgery based on a standardized questionnaire (modified SNOT 20) and the Glasgow Benefit Inventory. Health-related quality of life improved significantly in >90% of patients (p < 0.05). There were no serious complications or recurrences. As the treatment of choice functional endoscopic sinus surgery of paranasal fungus ball sinusitis is associated with exceptionally high patient satisfaction.

Simvastatin and Ginkgo biloba in the treatment of subacute tinnitus: a retrospective study of 94 patients.

OBJECTIVES: Studies suggest that hypercholesterolemia promotes the development of inner ear disorders such as tinnitus. However, the underlying pathomechanisms are still not clearly defined. METHODS: A retrospective study was performed to assess whether a reduction of serum cholesterol by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may result in a relief of subacute tinnitus. Remission rates of 58 patients were investigated after 4 months of treatment with simvastatin (40 mg). Results were compared to treatment with Ginkgo biloba (120 mg; n = 36) as control group. Differences between tinnitus score at the day of first treatment and after 4 months were used as main outcome measure. RESULTS: After treatment with simvastatin or G biloba, tinnitus score decreased from 41.3 ± 10.4 to 37.4 ± 17.3 and from 44.7 ± 11.2 to 41.2 ± 8.7, respectively. However, independently of the treatment regimen, differences of tinnitus scores were considered not significant. CONCLUSIONS: After administration of simvastatin over 4 months, this retrospective study has shown no significant efficacy in treatment of subacute tinnitus. For a more conclusive answer, further prospective, double-blind, and placebo-controlled studies with a larger number of patients are needed.

Surgical management of osteomas of the frontal recess and sinus: extending the limits of the endoscopic approach.

Osteomas are among the most common benign tumors of the paranasal sinuses. Symptomatic osteomas are most often found in the frontal recess and the frontal sinus. While the extranasal approach is still a part of the treatment concept for removing osteomas at this localization, over the last years the endoscopically controlled endonasal approach has greatly gained in importance due to the improved surgical equipment. We retrospectively analyzed the surgical indication, surgical approach and outcome of the removal of osteomas of the frontal recess and the frontal sinus performed at our hospital between 1996 and 2010. The exact surgical technique, intra- and postoperative complications, the duration of the hospital stay and the follow-up and subjective contentment of the patients were evaluated. With a total of 24 patients being included, the study comprises one of the largest groups of patients with osteomas of the frontal recess and sinus. Over the study period, the frequency of the endoscopic approach clearly increased. Previously suggested guidelines for the endoscopic resection of a frontal sinus osteoma turned out to be superseded. Endoscopically controlled resection even of large, adversely located osteomas of the frontal recess and the frontal sinus is becoming increasingly possible, but is still naturally limited by the individual anatomic conditions and the need for experienced surgeons.

Paranasal ossifying fibroma: endoscopic resection or wait and scan?

The ossifying fibroma is a fibro-osseous lesion that rarely occurs in the paranasal sinuses. Due to its tendency to behave locally aggressively, complete resection is generally recommended. A subdivision into the aggressive juvenile ossifying fibroma (JOF) and the less aggressive cemento-ossifying fibroma of the adult (COF) is clinically reasonable. The objective of the study was to retrospectively analyze the management and follow-up of the patients diagnosed with ossifying fibroma at our ENT-department from 2006 to 2010. A total of five patients were included, thereby comprising one of the largest case series of paranasal ossifying fibromas. In three patients an exclusively endoscopically controlled resection was performed. Two patients with asymptomatic COF declined surgery. Within the 2-year follow-up, no progression was detected. While the JOF should always be surgically treated, for the asymptomatic paranasal ossifying fibroma of the adult (COF) a wait-and-scan strategy, similar to that recommended for osteomas or fibrous dysplasia, could be an option in selected cases.

Therapeutic efficacy of icatibant in angioedema induced by angiotensin-converting enzyme inhibitors: a case series.

STUDY OBJECTIVE: The pathophysiology of angiotensin-converting enzyme inhibitor (ACEi)-induced angioedema most likely resembles that of hereditary angioedema, ie, it is mainly mediated by bradykinin-induced activation of vascular bradykinin B2 receptors. We hypothesize that the bradykinin B2 receptor antagonist icatibant might be an effective therapy for ACEi-induced angioedema. METHODS: Eight patients with acute ACEi-induced angioedema were treated with a single subcutaneous injection of icatibant. The outcome was assessed by the time to first improvement of symptoms, complete symptom relief, and drug safety. In addition, we retrospectively assessed the clinical course of 47 consecutive patients of our clinic with ACEi-induced angioedema. RESULTS: First symptom improvement after icatibant injection occurred at a mean time of 50.6 minutes (standard deviation [SD] 21 minutes) and complete relief of symptoms at 4.4 hours (SD 0.8 hours). No patient received tracheal intubation, other drug treatment, tracheotomy, or a second icatibant injection. There were no adverse effects except erythema occurring at the injection site. In the historical comparison group treated with methylprednisolone and clemastine, the mean time to complete relief of symptoms was 33 hours (SD 19.4 hours). Some of these patients received a tracheotomy (3/47), were intubated (2/47), or received a second dose of methylprednisolone (12/47). CONCLUSION: Although sample size limits the external validity of our results, the substantial decrease of time to complete symptom relief suggests that this new treatment is likely effective as a pharmacotherapeutic approach to treat ACEi-induced angioedema.

Comparison of two different local anaesthetic infiltrations for postoperative pain relief in tonsillectomy: a prospective, randomised, double blind, clinical trial.

In previous studies, it was shown that the post-tonsillectomy wound infiltration of bupivacaine can reduce postoperative pain. The objective of this study is to determine whether the postoperative wound infiltration with a mixture of bupivacaine, mepivacaine and adrenaline is more effective than the sole application of bupivacaine. A prospective, double-blind, randomized, control study included 30 patients scheduled for "cold steel" tonsillectomy. All patients obtained post-tonsillectomy infiltration of 6.25 mg bupivacaine alone on one side and 3.75 mg bupivacaine, 25 mg mepivacaine and 0.0125 mg epinephrine on the other side (intra-individual study design). Intake of analgesics and postoperative pain was assessed 0-6 days after surgery by visual analogue scale in inactivity and during swallowing by the nurse staff. Bleeding, dysphagia, pain, aspiration or extraordinary pain sensation were registered by the patient. The pain scores did not differ between the groups. All patients received systemic painkillers; 6 (20%) patients needed intravenous analgesics. Postoperative haemorrhage occurred in two patients without correlation to a certain local anaesthetic. Two patients developed sinus tachycardia for 2.5 min after epinephrine infiltration. Because of cost-effectiveness and complication rates, we recommend only post-tonsillectomy wound infiltration of bupivacaine. The injection should be placed in superficial muscle and connective tissue. A stringent systemic analgesia regime is indispensable for pain relief after tonsillectomy.

Total versus subtotal tonsillectomy for recurrent tonsillitis - a prospective randomized noninferiority clinical trial.

Background: For many years experts have called for randomized controlled trials to resolve the question whether tonsillectomy, which is associated with significant comorbidity, can be replaced by partial tonsillectomy in patients with recurrent tonsillitis.Objective: To find out whether subtotal tonsillectomy is a suitable therapeutic alternative to total tonsillectomy in adult patients with recurrent episodes of acute tonsillitis.Material and methods: Study design - Single-blind prospective non-inferiority randomized clinical trial with intraindividual design. Setting - 80 patients were recruited at a tertiary referral center. Subjects - Adult patients with recurrent tonsillitis received total tonsillectomy on one side and subtotal tonsillectomy on the other side after randomization. Main outcome measure was frequency of postoperative tonsillitis on the side of subtotal tonsillectomy and postoperative pharyngitis in the former tonsil area on the side of total tonsillectomy. The study was registered in the German Clinical Trials Register (DRKS-ID: DRKS00015628).Results: Within 12 months none of the subjects suffered from recurrent tonsillitis after subtotal tonsillectomy. Subtotal tonsillectomy caused less pain than total tonsillectomy.Conclusion: Subtotal tonsillectomy might be an alternative treatment option associated with lower morbidity than total tonsillectomy in adults with recurrent tonsillitis.

Application methods of local anaesthetic infiltrations for postoperative pain relief in tonsillectomy: a prospective, randomised, double-blind, clinical trial.

Perioperative local anaesthetics are often used to reduce the postoperative pain in tonsillectomy. There exist three different ways of applying local anaesthetics: (1) pre-incisional peritonsillar; (2) post-tonsillectomy wound infiltration; (3) post-tonsillectomy packing with soaked gauze. The objective of the study is the evaluation of differences of pain reduction comparing the three different techniques of application. The study design mainly includes intra-individual, prospective and double-blinded. One hundred and eighty patients (3-45 years) with recurrent tonsillitis were included. The charts of 156 were eligible for analysis. Bupivacaine was applied on both sides randomized in different ways. Pain on each side was registered for 6 days on the ward by a blinded nurse. When directly compared with the other two application methods, the post-tonsillectomy injection of bupivacaine provides significantly better results during the monitored time period. Postoperative bleeding was observed in 11 (7.3%) cases without any correlation to an application procedure. No other adverse effects were observed. In conclusion, post-tonsillectomy infiltration of the wounds with bupivacaine is superior to pre-incisional infiltration technique as well as post-tonsillectomy packing of the wounds with 0.5% bupivacaine-soaked gauze swab.

Does surgical resection of pulmonary metastases of head and neck cancer improve survival?

BACKGROUND: The prognosis of patients with metastasized head and neck cancer is poor. Limited experience exists with the benefit of resection of lung metastases and systematic mediastinal and hilar lymph node dissection on survival of patients with head and neck carcinoma. METHODS: Eighty patients undergoing metastasectomy for pulmonary metastases of primary head and neck cancer entered the study. Multivariate analysis was performed by Cox regression analysis. Survival differences between patients operated and those not operated on were analyzed by matched pair analysis. RESULTS: From 1984 until 2006, pulmonary metastases were diagnosed in 332 patients treated for head and neck cancer; 80 of these were admitted to our department for resection. Metastases of the primary head and neck tumor were confirmed histologically in 67 patients. The median overall survival after resection of lung metastases was 19.4 months and was statistically significantly better compared with patients who were not operated on (P < .001). The multivariate analysis after metastasectomy revealed that incomplete resection of pulmonary lesions, complications associated with surgery, and adjuvant therapy of the primary tumor are independent negative prognostic factors for survival. We observed a trend to improved survival in patients without hilar or mediastinal lymph node metastases. CONCLUSION: The survival rate of patients operated on was statistically significantly higher than that of patients with conservative treatment. Even patients with multiple or bilateral pulmonary lesions after curative treatment of a primary tumor should be operated on if there is no contraindication against an extended surgical procedure and a complete resection of the metastases seems achievable.