Characterization of Fat Used for the Optimization of the Soft Tissue Envelope of the Nose in Rhinoplasty.

Septorhinoplasty (SRP) is one of the most common aesthetic procedures worldwide. A thin or scarred soft tissue envelope, especially in the context of secondary SRP, can lead to unpredictable scarring, shrinkage, and discoloration of the skin. Other than the careful preparation of the soft tissue mantle, no gold standard exists to minimize the above-mentioned risks. Our aim was to create a thin "separation layer" between the nasal bridge (osseous and cartilaginous) and the skin envelope by autologous fat transfer with the addition of platelet-rich fibrin (PRF) to conceal small irregularities, to improve the quality of the skin soft tissue mantle, and to optimize the mobility of the skin. We report 21 patients who underwent SRP on a voluntary basis. All patients had either thin skin and/or revision SRP with scarring. Macroscopic fat harvested from the periumbilical or rib region was minced and purified. PRF was obtained by centrifugation of autologous whole blood samples and mixed with the fat to form a graft, which was then transferred to the nasal dorsum. Postoperative monitoring of graft survival included sonography and magnetic resonance imaging (MRI) of the nose. The harvested adipose tissue was also analyzed in vitro. In the postoperative follow-up after 1 year, survival of the adipose tissue was demonstrated in all patients by both sonography and MRI. The in vitro analysis showed interindividual differences in the quantity, size, and quality of the transplanted adipocytes. Camouflage of the nasal bridge by using adipose tissue was beneficial for the quality of the skin soft tissue mantle and hence represents a good alternative to known methods. Future aims include the ability to assess the quality of adipose tissue to be transplanted based on clinical parameters. Level of evidence: N/A.

Association between venous thromboembolism rates and different prophylactic anticoagulation regimens in patients undergoing free flap reconstruction of the head and neck region.

BACKGROUND: Venous Thromboembolism (VTE) is a serious complication after free tissue transfer to the head and neck (H&N). However, an optimal antithrombotic prophylaxis protocol is not defined in the literature. Enoxaparin 30 mg twice daily (BID) and heparin 5000 IU three times daily (TID) are among the most commonly used regimens for chemoprophylaxis. However, no studies compare these two agents in the H&N population. METHODS: A cohort study of patients who underwent free tissue transfer to H&N from 2012 to 2021 and received either enoxaparin 30 mg BID or Heparin 5000 IU TID postoperatively. Postoperative VTE and hematoma events were recorded within 30 days of index surgery. The cohort was divided into two groups based on chemoprophylaxis. VTE and hematoma rates were compared between the groups. RESULTS: Out of 895 patients, 737 met the inclusion criteria. The mean age and Caprini score were 60.6 [SD 12.5] years and 6.5 [SD 1.7], respectively. 234 [31.88%] were female. VTE and hematoma rates among all patients were 4.47% and 5.56%, respectively. The mean Caprini score between the enoxaparin (n = 664) and heparin (n = 73) groups was not statistically significant (6.5 ± 1.7 vs.6.3 ± 1.3, p = 0.457). The VTE rate in the enoxaparin group was significantly lower than in the heparin group (3.9% vs. 9.6%; OR: 2.602, 95% CI: 1.087-6.225). Hematoma rates were similar between the two groups (5.5% vs. 5.6%; OR: 0.982, 95% CI: 0.339-2.838). CONCLUSIONS: Enoxaparin 30 mg BID was associated with a lower VTE rate while maintaining a similar hematoma rate compared to heparin 5000 units TID. This association may support the use of enoxaparin over heparin for VTE chemoprophylaxis in H&N reconstruction.

Surgical and Nonsurgical Management of the Nasal Skin-Soft Tissue Envelope.

Management of the skin-soft tissue envelope (SSTE) in rhinoplasty is challenging and critical for the overall outcome. The preoperative identification of patients with thick or thin skin and with preexisting skin conditions may contribute significantly to the postsurgical result. Most publications and textbooks focus on the management of the osseocartilaginous framework, but the SSTE management is often not addressed in detail. However, nonsurgical treatments, such as skin preconditioning, topical steroid-injections, oral isotretinoin, and topical vitamin A derivatives, may provide strong benefits. In this article, we reviewed the literature to present a comprehensive review on the available surgical and nonsurgical approaches pre-, intra-, and postoperatively dealing with SSTE in rhinoplasty.

Optimization of the Soft Tissue Envelope of the Nose in Rhinoplasty Utilizing Fat Transfer Combined with Platelet-Rich Fibrin.

A thin or damaged skin soft tissue envelope may cause concerns in primary and secondary rhinoplasty. During postoperative healing, unpredictable scarring and contraction may occur and lead to significant aesthetic and trophic sequelae. Besides a meticulous surgical technique, there are no reliable techniques to prevent long-term skin damage and shrinkage. Fat transfer with addition of platelet-rich fibrin (PRF) harbors the possibility of local soft tissue regeneration and skin rejuvenation through growth factors and mesenchymal stem cells. It may also facilitate the creation of a thin fat layer on the dorsum to prevent shrink-wrap forces and conceal small irregularities. The goal is to provide evidence for the feasibility, durability, and beneficial effect of diced macrofat transfer bonded with PRF on the nasal dorsum. We present the technique of fat transfer conjugated with PRF as a nasal dorsal graft. Clinical endpoints were the prevention of trophic disturbances and atrophy at a 1-year postoperative follow-up. We present the skin mobility test as a clinical indicator of a healthy soft tissue envelope. The presented case series consists of 107 rhinoplasties. Fat was harvested in the umbilical or costal region. PRF was created by centrifugation of autologous whole blood samples. Macrofat was diced, cleaned, and bonded with PRF. The compound transplants were transferred to the nasal dorsum. There were no perioperative complications or wound-healing issues. Mean follow-up was 14 months. Clinical inspection showed good skin quality and no signs of shrinkage, marked scarring, or color changes with positive skin mobility test in all patients. Survival of fat was confirmed by ultrasonography and magnetic resonance imaging. Diced macrofat transfer in conjunction with PRF to the nasal dorsum is a feasible and safe method. A beneficial effect on the soft tissue envelope is demonstrated as well as the prevention of shrink-wrap forces.

OpenMS: a flexible open-source software platform for mass spectrometry data analysis.

High-resolution mass spectrometry (MS) has become an important tool in the life sciences, contributing to the diagnosis and understanding of human diseases, elucidating biomolecular structural information and characterizing cellular signaling networks. However, the rapid growth in the volume and complexity of MS data makes transparent, accurate and reproducible analysis difficult. We present OpenMS 2.0 (http://www.openms.de), a robust, open-source, cross-platform software specifically designed for the flexible and reproducible analysis of high-throughput MS data. The extensible OpenMS software implements common mass spectrometric data processing tasks through a well-defined application programming interface in C++ and Python and through standardized open data formats. OpenMS additionally provides a set of 185 tools and ready-made workflows for common mass spectrometric data processing tasks, which enable users to perform complex quantitative mass spectrometric analyses with ease.

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.).

Systematic Review of Quality-of-Life Measurement After Aesthetic Rhinoplasty.

INTRODUCTION: The assessment of outcomes in aesthetic rhinoplasty is highly relevant because patient satisfaction and improved health-related quality of life (QoL) are the predominant factors in determining success. The patient-reported outcome measures (PROMs) employed in rhinoplasty research studies are remarkably diverse, thus yielding difficulties with data analysis. The aim of this article is to provide a comprehensive review of the literature to reveal the relevance of the QoL assessment for rhinosurgeons. METHODS: A systematic literature search with the terms "Rhinoplasty" and "Quality of Life" was conducted using PubMed/MEDLINE, Google Scholar and Cochrane databases. Primarily, all publications related to QoL following aesthetic rhinoplasty between 2002 and 2017 were identified. As a secondary selection, we focused on articles with a prospective study design, a significant cohort size (at least 50 patients) and a follow-up period of at least 6 months after aesthetic rhinoplasty. RESULTS: A total of 62 PROM studies assessing QoL following aesthetic rhinoplasties were obtained. We ascertained an increasing publication rate of QoL articles over the last 15 years. Only 17 studies satisfied comprehensive inclusion criteria of a high qualitative study selection. The Rhinoplasty Outcome Evaluation was the most frequently used QoL questionnaire of the secondary selection (70.6%). The total number of 16 various questionnaires exhibit high heterogeneity. CONCLUSION: Our data strengthen the increasing importance of the assessment of QoL after rhinoplasty. Despite a lack of reliable publications with considerable heterogeneity and large variability in outcomes, functional-aesthetic rhinoplasty leads to a significant improvement of patient's health-related QoL. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Chirurgische Versorgung von Hautkrebs und Trauma im mittleren Drittel der Ohrmuschel.

Die Hauptursachen erworbener Ohrmuscheldefekte sind chirurgische Behandlung von Hauttumoren und Traumata. Wegen der komplexen Anatomie des Außenohrs ist die chirurgische Rekonstruktion von Defekten in dieser Region für Operateure herausfordernd, insbesondere wenn die mittlere Helix und Anthelix von größeren Weichteil- und Knorpelverlusten betroffen sind. Wir stellen hier die wichtigsten Techniken zur Rekonstruktion großer Defekte der mittleren Helix und Anthelix sowie die Vor- und Nachteile jedes chirurgischen Verfahrens vor. Bei älteren, multimorbiden Patienten werden meist einstufige Verfahren mit primärem Verschluss/Keilexzision angewandt; es können aber auch mehrere komplexe chondrokutane, retroaurikuläre, temporoparietale Vollhautlappen-Verfahren durchgeführt werden, um ein normal aussehendes Ohr zu rekonstruieren. Die aurikuläre Rekonstruktion großer Defekte der mittleren Helix-Anthelix Region erfordert gute Kenntnisse der Ohrmuschel-Anatomie und der verschiedenen chirurgischen Verfahren zur Korrektur solcher Defekte.

Surgical management of skin cancer and trauma involving the middle third of the auricle.

The main causes of acquired auricular defects are surgical treatment of skin tumors and trauma. Due to the complex anatomy of the external ear, surgical reconstruction of defects in this area is challenging for surgeons, especially in case of midhelix-antihelix involvement with significant loss of soft tissue and cartilage. Our purpose is to illustrate the main reconstructive techniques of large midhelix and antihelix defects, as well as the advantages or disadvantages associated with each surgical procedure. Primary closure/wedge technique is mainly used in elderly, multimorbid subjects where single-stage procedures are desirable, but several complex chondrocutaneous, retroauricular, temporoparietal full-thickness flap procedures can also be used to recreate an ear with normal appearance. Auricular reconstruction of large midhelix-antihelix defects requires a good knowledge of auricular anatomy and the various surgical procedures available for such defects.

[Application of vacuum wound therapy with split thickness skin grafts in the head and neck area]. / Anwendung von Vakuum-Wundtherapie bei Spalthaut-Transplantaten im Kopf-Hals-Bereich.

OBJECTIVE: In vacuum wound therapy (VAC) a negative pressure can continuously clean effusions and enhance the formation of granulation tissue significantly. In visceral, trauma and burns surgery this technique is used frequently in critical wounds. In the head and neck area there is limited experience and publications. Especially in the combined use of split-thickness-skin grafts (STSG) and VAC there is no published evidence. MATERIAL AND METHODS: A retrospective database analysis was done and resulted in 36 single VAC therapies in 13 patients. They were treated between 2012 and 2017 in the Department of Otorhinolaryngology of the University Medical Center Ulm, Germany. A data analysis was performed relating to indications, diagnoses, comorbidities as well as the clinical course and outcome with special focus on STSG. RESULTS: Besides classical indications as pharyngo-cutaneous fistulas and troublesome would healing after flap surgery, 7 cases of VAC use with split-thickness skin grafts were identified. The median treatment duration was 11 days, the VAC dressing was changed twice in average, the median negative pressure was 70 mmHg. Wound closure was successful in 13/13 cases, in 7/13 cases wound closure was achieved by split-thickness skin graft with synchronous VAC therapy, 4/13 cases showed healing by secondary intention, in 2/13 cases a local or distant flap was used. CONCLUSIONS: We first describe the successful use of VAC therapy in combination with STSG in the head and neck area. This was effective in radiated patients and in critically ill patients with sepsis and necrotizing fasciitis.

Diagnostic accuracy of 18F-FDG PET/CT and MR imaging in patients with adenoid cystic carcinoma.

BACKGROUND: The aim of this study was to evaluate the value of 18F-FDG PET/CT (PET/CT) and MRI for local and/or whole-body restaging of adenoid cystic carcinoma of the head and neck (ACC). METHODS: Thirty-six patients with ACC underwent conventional MRI of the head and neck and a whole-body PET/CT and were analysed with regards to detection of a local tumor recurrence, lymph node or distant metastases. A consensus interpretation of all available imaging data was used as reference standard. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values were calculated for MRI and PET/CT. RESULTS: The sensitivity of PET/CT and MRI was 96% (89%), specificity 89% (89%), PPV 96% (96%), NPV 89% (73%) and accuracy 94% (89%) for detection of local tumors. Additionally, PET/CT revealed lymph node metastases in one patient and distant metastases in 9/36 patients. In three patients secondary primaries were found. CONCLUSIONS: Whole-body PET/CT in addition to MRI of the head and neck improves detection of local tumour and metastastic spread in ACC.

[Virtual Planning of Prosthetic Treatment of the Orbit]. / Virtuelle Planung bei der epithetischen Orbitaversorgung.

Optimal positioning of bone-anchored implants in the treatment of patients with orbital prosthesis is challenging. The definition of implant axis as well as the positioning of the implants is important to prevent failures in prosthetic rehabilitation in these patients. We performed virtual planning of enossal implants at a base of a standard fan beam CT scan using the software CoDiagnostiX™ (DentalWings, Montréal, Canada). By 3D-printing a surgical guide for drilling and implant insertion was manufactured (Med-610™, Stratasys, Rehovot, Israel). An orbital exenteration was performed in a patient after shrinkage of the eyelids 20 years after enucleation and radiation of the orbit due to rhabdomyosarcoma. 4 Vistafix-3 implants (Cochlear™, Cochlea, Centennial, USA) were primarily inserted after resection with the help of the 3D-surgical guide. Prosthetic rehabilitation could be achieved as preplanned to a predictable result. The individual prosthesis of the orbit showed good functional and esthetic outcome. The virtual 3D-planning of endosseous implants for prosthetic orbital and periorbital reconstruction is easy to use and facilitates optimal placement of implants especially in posttherapeutically altered anatomic situations.

From the desktop to the grid: scalable bioinformatics via workflow conversion.

BACKGROUND: Reproducibility is one of the tenets of the scientific method. Scientific experiments often comprise complex data flows, selection of adequate parameters, and analysis and visualization of intermediate and end results. Breaking down the complexity of such experiments into the joint collaboration of small, repeatable, well defined tasks, each with well defined inputs, parameters, and outputs, offers the immediate benefit of identifying bottlenecks, pinpoint sections which could benefit from parallelization, among others. Workflows rest upon the notion of splitting complex work into the joint effort of several manageable tasks. There are several engines that give users the ability to design and execute workflows. Each engine was created to address certain problems of a specific community, therefore each one has its advantages and shortcomings. Furthermore, not all features of all workflow engines are royalty-free -an aspect that could potentially drive away members of the scientific community. RESULTS: We have developed a set of tools that enables the scientific community to benefit from workflow interoperability. We developed a platform-free structured representation of parameters, inputs, outputs of command-line tools in so-called Common Tool Descriptor documents. We have also overcome the shortcomings and combined the features of two royalty-free workflow engines with a substantial user community: the Konstanz Information Miner, an engine which we see as a formidable workflow editor, and the Grid and User Support Environment, a web-based framework able to interact with several high-performance computing resources. We have thus created a free and highly accessible way to design workflows on a desktop computer and execute them on high-performance computing resources. CONCLUSIONS: Our work will not only reduce time spent on designing scientific workflows, but also make executing workflows on remote high-performance computing resources more accessible to technically inexperienced users. We strongly believe that our efforts not only decrease the turnaround time to obtain scientific results but also have a positive impact on reproducibility, thus elevating the quality of obtained scientific results.

Mass-Spectrometry-Based Proteomics Reveals Organ-Specific Expression Patterns To Be Used as Forensic Evidence.

Standard forensic procedures to examine bullets after an exchange of fire include a mechanical or ballistic reconstruction of the event. While this is routine to identify which projectile hit a subject by DNA analysis of biological material on the surface of the projectile, it is rather difficult to determine which projectile caused the lethal injury--often the crucial point with regard to legal proceedings. With respect to fundamental law it is the duty of the public authority to make every endeavor to solve every homicide case. To improve forensic examinations, we present a forensic proteomic method to investigate biological material from a projectile's surface and determine the tissues traversed by it. To obtain a range of relevant samples, different major bovine organs were penetrated with projectiles experimentally. After tryptic "on-surface" digestion, mass-spectrometry-based proteome analysis, and statistical data analysis, we were able to achieve a cross-validated organ classification accuracy of >99%. Different types of anticipated external variables exhibited no prominent influence on the findings. In addition, shooting experiments were performed to validate the results. Finally, we show that these concepts could be applied to a real case of murder to substantially improve the forensic reconstruction.

LFQProfiler and RNP(xl): Open-Source Tools for Label-Free Quantification and Protein-RNA Cross-Linking Integrated into Proteome Discoverer.

Modern mass spectrometry setups used in today's proteomics studies generate vast amounts of raw data, calling for highly efficient data processing and analysis tools. Software for analyzing these data is either monolithic (easy to use, but sometimes too rigid) or workflow-driven (easy to customize, but sometimes complex). Thermo Proteome Discoverer (PD) is a powerful software for workflow-driven data analysis in proteomics which, in our eyes, achieves a good trade-off between flexibility and usability. Here, we present two open-source plugins for PD providing additional functionality: LFQProfiler for label-free quantification of peptides and proteins, and RNP(xl) for UV-induced peptide-RNA cross-linking data analysis. LFQProfiler interacts with existing PD nodes for peptide identification and validation and takes care of the entire quantitative part of the workflow. We show that it performs at least on par with other state-of-the-art software solutions for label-free quantification in a recently published benchmark ( Ramus, C.; J. Proteomics 2016 , 132 , 51 - 62 ). The second workflow, RNP(xl), represents the first software solution to date for identification of peptide-RNA cross-links including automatic localization of the cross-links at amino acid resolution and localization scoring. It comes with a customized integrated cross-link fragment spectrum viewer for convenient manual inspection and validation of the results.

Time-resolved characterization of cAMP/PKA-dependent signaling reveals that platelet inhibition is a concerted process involving multiple signaling pathways.

One of the most important physiological platelet inhibitors is endothelium-derived prostacyclin which stimulates the platelet cyclic adenosine monophosphate/protein kinase A (cAMP/PKA)-signaling cascade and inhibits virtually all platelet-activating key mechanisms. Using quantitative mass spectrometry, we analyzed time-resolved phosphorylation patterns in human platelets after treatment with iloprost, a stable prostacyclin analog, for 0, 10, 30, and 60 seconds to characterize key mediators of platelet inhibition and activation in 3 independent biological replicates. We quantified over 2700 different phosphorylated peptides of which 360 were significantly regulated upon stimulation. This comprehensive and time-resolved analysis indicates that platelet inhibition is a multipronged process involving different kinases and phosphatases as well as many previously unanticipated proteins and pathways.

Evaluation of Customized Prosthesis for Irregularly Formed Tracheostoma After Laryngectomy.

BACKGROUND: After laryngectomy, the tracheostoma forms the functional center for breathing and phonation. An occasionally occurring but typical problem can arise from an oversized and/or irregularly formed tracheostoma, hampering the temporary occlusion necessary for sufficient speech production. As an alternative to a surgical correction of the tracheostoma, an individually adjusted stoma silicone prosthesis may be used. MATERIALS AND METHODS: Twenty-one patients suffering from irregularly formed tracheostoma after laryngectomy followed by insertion of a speech valve were provided with a silicone tracheostomal prosthesis. They underwent subjective assessment of voice quality and breathing function according to a standardized general questionnaire and to the Voice Handicap Index (VHI). Furthermore, a clinical evaluation was performed including detection of peristomal leakage and phonation time. RESULTS AND DISCUSSION: Patients described a significant improvement of voice production with the tracheostomal prosthesis (averagely graded as 1.9 with and 3.2 without prosthesis, P = .0026). Breathing was also slightly improved by the prosthesis with an average grade of 1.7 compared to 2.3 with a conventional cannula (P = .063). There was a strong correlation between self-evaluation and the total score of the VHI after insertion of the prosthesis (P < .0001). Minor local skin reactions caused by the adhesive were described by 5 of the 21 patients. CONCLUSIONS: A tracheostomal prosthesis represents an efficient alternative to surgical revision of irregularly formed tracheostoma after laryngectomy, enhancing voice production and breathing function.

Dermatological assessment of thick-skinned patients before rhinoplasty-what may surgeons ask for?

Rhinoplasty is considered a very challenging surgery since minimal changes of this central area of the face may significantly impact a person's appearance and self-awareness. This is even more challenging in thick-skinned patients because results are less predictable, and changes to the osseocartilaginous framework (OCF) may not be sufficiently visible due to the blanket effect of the thick skin. Furthermore, pre-existing skin conditions may exacerbate following surgery. Therefore, managing patients with extremely thick skin or patients who suffer from pre-existing dermatological conditions such as rosacea or acne requires a synergy of surgeons and dermatologists to achieve optimal results. In this article, we review the most significant pre- and post-surgical regimens that surgeons and dermatologists should apply in selected patients to achieve optimal results after rhinoplasty.