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Featured researches published by Leila Harhaus.


Surgical Innovation | 2016

Indocyanine Green Fluorescence for Free-Flap Perfusion Imaging Revisited Advanced Decision Making by Virtual Perfusion Reality in Visionsense Fusion Imaging Angiography

Amir K. Bigdeli; Emre Gazyakan; Volker J. Schmidt; Frederick Hernekamp; Leila Harhaus; Thomas Henzler; Thomas Kremer; Ulrich Kneser; Christoph Hirche

Background. Near-infrared indocyanine green video angiography (ICG-NIR-VA) has been introduced for free-flap surgery and may provide intraoperative flap designing as well as postoperative monitoring. Nevertheless, the technique has not been established in clinical routine because of controversy over benefits. Improved technical features of the novel Visionsense ICG-NIR-VA surgery system are promising to revisit the field of application. It features a unique real-time fusion image of simultaneous NIR and white light visualization, with highlighted perfusion, including a color-coded perfusion flow scale for optimized anatomical understanding. Methods. In a feasibility study, the Visionsense ICG-NIR-VA system was applied during 10 free-flap surgeries in 8 patients at our center. Indications included anterior lateral thigh (ALT) flap (n = 4), latissimus dorsi muscle flap (n = 1), tensor fascia latae flap (n = 1), and two bilateral deep inferior epigastric artery perforator flaps (n = 4). The system was used intraoperatively and postoperatively to investigate its impact on surgical decision making and to observe perfusion patterns correlated to clinical monitoring. Results. Visionsense ICG-NIR-VA aided assessing free-flap design and perfusion patterns in all cases and correlated with clinical observations. Additional interventions were performed in 2 cases (22%). One venous anastomosis was revised, and 1 flap was redesigned. Indicated by ICG-NIR-VA, 1 ALT flap developed partial flap necrosis (11%). Conclusions. The Visionsense ICG-NIR-VA system allowed a virtual view of flap perfusion anatomy by fusion imaging in real-time. The system improved decision making for flap design and surgical decisions. Clinical and ICG-NIR-VA parameters correlated. Its future implementation may aid in improving outcomes for free-flap surgery, but additional experience is needed to define its final role.


PLOS ONE | 2017

Usefulness of bone scintigraphy for the diagnosis of Complex Regional Pain Syndrome 1: A systematic review and Bayesian meta-analysis

Maria M. Wertli; Florian Brunner; Johann Steurer; Ulrike Held; Leila Harhaus

Background Since 2007, the Budapest criteria are recommended for the diagnosis of Complex Regional Pain Syndrome (CRPS) 1. The usefulness of bone scintigraphy (BS, index test) for the diagnosis of CRPS 1 remains controversial. Imperfect reference tests (RT) result in underestimation of the diagnostic accuracy of BS. Further, biased results can occur when a dependency between the RT and BS exists. The objective was to assess the impact of different RTs, specifically the Budapest criteria, and the assumed imperfect nature of the RT on the diagnostic accuracy of BS. Further, we analyzed the association between baseline characteristics and positive BS in patients with CRPS 1. Methods Systematic literature review and Bayesian meta-analysis to assess the test accuracy of BS with and without accounting for the imperfect nature of the RT. We examined correlations (Spearman correlation coefficients / Wilcoxon tests) between baseline characteristics and the proportion of positive BS in patients with CRPS 1. Results The pooled sensitivity was 0.804 (95% credible interval (CI) 0.225–1.0, 21 studies) and specificity 0.853 (95%CI 0.278–1.00). Sensitivity and specificity of BS increased when accounting for the imperfect nature of the RT. However, in studies using Budapest criteria as reference, the sensitivity decreased (0.551; 95% CI 0.046–1) and the specificity increased (0.935; 95% CI 0.306–1). Shorter disease duration and a higher proportion of males were associated with a higher proportion of positive BS (27 studies, disease duration <52 weeks Wilcoxon test p = 0.047, female proportion Spearman correlation −0.63, p = 0.009). Conclusion Compared to the accepted Budapest diagnostic criteria BS cannot be used to rule-in the diagnosis of CRPS 1. In patients with negative BS CRPS 1 is less likely the underlying illness. Studies using older or no diagnostic criteria should not be used to evaluate the diagnostic accuracy of BS in CRPS 1.


Journal of Tissue Engineering and Regenerative Medicine | 2018

Axially Vascularized Tissue Engineered Bone Constructs Retain their In‐Vivo Angiogenic and Osteogenic Capacity After High Dose Irradiation

Ahmad Eweida; Oliver Frisch; Frank A. Giordano; Jens Fleckenstein; Frederik Wenz; Marc A. Brockmann; Matthias Schulte; Volker J. Schmidt; Ulrich Kneser; Leila Harhaus

In order to introduce bone tissue engineering to the field of oncological reconstruction, we are investigating for the first time the effect of various doses of ionizing irradiation on axially vascularized bone constructs. Synthetic bone constructs were created and implanted in 32 Lewis rats. Each construct was axially vascularized through an arteriovenous loop made by direct anastomosis of the saphenous vessels. After 2 weeks, the animals received ionizing irradiation of 9 Gy, 12 Gy and 15 Gy, and were accordingly classified to groups I, II and III, respectively. Group IV was not irradiated and acted as a control. Tissue generation, vascularity, cellular proliferation and apoptosis were investigated either 2 or 5 weeks after irradiation through micro‐computed tomography, histomorphometry and real‐time polymerase chain reaction (PCR). At 2 weeks after irradiation, tissue generation and central vascularity were significantly lower and apoptosis was significantly higher in groups II and III than group IV, but without signs of necrosis. Cellular proliferation was significantly lower in groups I and II. After 5 weeks, the irradiated groups showed improvement in all parameters in relation to the control group, indicating a retained capacity for angiogenesis after irradiation. PCR results confirmed the expression of osteogenesis‐related genes in all irradiated groups. Dense collagen was detected 5 weeks after irradiation, and one construct showed discrete islands of bone indicating a retained osteogenic capacity after irradiation. This demonstrates for the first time that axial vascularization was capable of supporting a synthetic bone construct after a high dose of irradiation that is comparable to adjuvant radiotherapy. Copyright


Journal of Cellular and Molecular Medicine | 2015

The vascularized periosteum flap as novel tissue engineering model for repair of cartilage defects.

Leila Harhaus; Jung-Ju Huang; Shu-wei Kao; Yen-Lin Wu; Gina A. Mackert; Bernd Höner; Ming-Huei Cheng; Ulrich Kneser; Chao-Min Cheng

Periosteum is a promising tissue engineering scaffold in research of cartilage repair; so far however, periosteum transfers have not been realized successfully because of insufficient nourishment of the graft. In a translational approach we, for the first time, designed a vascularized periosteum flap as ‘independent’ biomaterial with its own blood supply to address this problem and to reconstruct circumscript cartilage defects. In six 3‐month‐old New Zealand rabbits, a critical size cartilage defect of the medial femur condyle was created and covered by a vascularized periosteum flap pedicled on the saphenous vessels. After 28 days, formation of newly built cartilage was assessed macroscopically, histologically and qualitatively via biomechanical compression testing, as well as on molecular biological level via immunohistochemistry. All wounds healed completely, all joints were stable and had full range of motion. All flaps survived and were perfused through their pulsating pedicles. They showed a stable attachment to the bone, although partially incomplete adherence. Hyaline cartilage with typical columnar cell distribution and positive Collagen II staining was formed in the transferred flaps. Biomechanical testing revealed a significantly higher maximum load than the positive control, but a low elasticity. This study proved that vascularization of the periosteum flap is the essential step for flap survival and enables the flap to transform into cartilage. Reconstruction of circumscript cartilage defects seems to be possible. Although these are the first results out of a pilot project, this technique, we believe, can have a wide range of potential applications and high relevance in the clinical field.


Journal of Biomedical Materials Research Part A | 2017

Preparation and Characterization of 45S5 Bioactive Glass‐based Scaffolds Loaded with PHBV Microspheres with Daidzein Release Function

Víctor I. Macías-Andrés; Wei Li; Ena A. Aguilar-Reyes; Yaping Ding; Judith A. Roether; Leila Harhaus; Carlos A. León-Patiño; Aldo R. Boccaccini

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microsphere loaded 45S5 bioactive glass (BG) based scaffolds with drug releasing capability have been developed. PHBV microspheres with a mean particle size 4 ± 2 μm loaded with daidzein were obtained by oil-in-water single emulsion solvent evaporation method and applied to the surface of BG scaffolds by dip coating technique. The morphology, in vitro bioactivity in simulated body fluid (SBF), mechanical properties and drug release kinetics of microsphere loaded scaffolds were studied. The microspheres were shown to be homogeneously dispersed on the scaffold surfaces. It was confirmed that hydroxyapatite crystals homogeneously grew not only on the surface of the scaffold but also on the surface of the microspheres within 3 days of immersion in SBF. The daidzein release from the microsphere loaded scaffolds lasted almost 1 month and was determined to be diffusion controlled. The microsphere loaded BG scaffolds with daidzein releasing capability obtained in this study are a candidate for bone tissue engineering.


Annals of Plastic Surgery | 2017

Collagen-Elastin and Collagen-Glycosaminoglycan Scaffolds Promote Distinct Patterns of Matrix Maturation and Axial Vascularization in Arteriovenous Loop–Based Soft Tissue Flaps

Volker J. Schmidt; Johanna O. Wietbrock; Nico Leibig; Torsten Gloe; Dominic Henn; J. Frederik Hernekamp; Leila Harhaus; Ulrich Kneser

Introduction Autologous free flaps are the criterion standard for reconstructions of complex soft tissue defects; however, they are limited by donor-site morbidities. The arteriovenous (AV) loop model enables the generation of soft tissue constructs based on acellular dermal matrices with a functional microvasculature and minimal donor site morbidity. The ideal scaffold for AV loop–based tissue engineering has not been determined. Methods AV loops were placed into subcutaneous isolation chambers filled with either a collagen-elastin scaffold or a collagen-glycosaminoglycan scaffold in the thighs of rats. Matrix elasticity, neoangiogenesis, cell migration, and proliferation were compared after 14 and 28 days. Results Mean vessel count and area had increased in both matrices at 28 compared with 14 days. Collagen-elastin matrices showed a higher mean vessel count and area compared with collagen-glycosaminoglycan matrices at 14 days. At 28 days, a more homogeneous vascular network and higher cell counts were observed in collagen-elastin matrices. Collagen-glycosaminoglycan matrices, however, exhibited less volume loss at day 28. Conclusions Collagen-based scaffolds are suitable for soft tissue engineering in conjunction with the AV loop technique. These scaffolds exhibit distinct patterns of angiogenesis, cell migration, and proliferation and may in the future serve as the basis of tissue-engineered free flaps as an individualized treatment concept for critical wounds.


Journal of Foot & Ankle Surgery | 2017

Surgical Revascularization—An Innovative Approach to the Treatment of Talar Osteonecrosis Dissecans Stages II and III

Victoria Struckmann; Leila Harhaus; Rainer Simon; Christoph Woelfl; Jan von Recum; Jörn Thiele; Ulrich Kneser; Thomas Kremer

Abstract Talar osteonecrosis dissecans is caused by osseous malperfusion, leading to destruction of the talar bone. The current reference standard for advanced stages lacking arthrosis is core decompression, followed by autologous cancellous bone grafting. However, talar revascularization has not been observed in a subset of patients after this procedure. Microsurgical vascularized bone grafting can improve outcomes by the induction of angiogenesis. We present the 1‐year follow‐up data from 3 patients with talar osteonecrosis dissecans, who had undergone free vascularized medial femoral condyle autotransplantation. The patients were evaluated preoperatively and 3, 6, and 12 months postoperatively. The active range of motion, pain (visual analog scale [VAS]), and American Orthopaedic Foot and Ankle Society ankle‐hindfoot scale, and lower extremity functional scale were used. Osteonecrosis dissecans stage II was seen in patient 1 (aged 27 years) and stage III in patients 2 (aged 18 years) and 3 (aged 41 years). Preoperative pain of the ankle was recorded as VAS score of 3 by patients 1 and 2 and VAS score of 6 by patient 3. At 12 months postoperatively, patients 1 and 2 recorded a VAS score of 2 and patient 3, a VAS score of 0. All patients showed improvement in the lower extremity functional scale and American Orthopaedic Foot and Ankle Society scale scores. After 6 and 12 months, magnetic resonance imaging showed a well‐vascularized femoral condyle incorporated into the talus in all the patients. Autotransplantation of vascularized bone grafts from the medial femoral condyle is a promising technique for surgical revascularization of talar osteonecrosis dissecans stage II and III. &NA; Level of Clinical Evidence: 4


Handchirurgie Mikrochirurgie Plastische Chirurgie | 2017

Versorgungsstrategie von Nervenverletzungen bei schwerem Weichteilschaden. Konsensus-Statement der Deutschsprachigen Arbeitsgemeinschaft für Mikrochirurgie der peripheren Nerven und Gefäße

Leila Harhaus; Christoph Hirche; Riccardo E. Giunta; Oskar C. Aszmann; Frank Siemers; Ulrich Kneser; Marcus Lehnhardt

Nerve injuries with severe soft tissue damage are rare and demand a complex and individualized treatment approach, in order to limit medical and socioeconomic consequences. Since uniform systematic evidence so far is lacking, inconsistent therapy standards are implemented depending on individual experiences and background of respective microsurgeons.In order to provide best conditions for further healing, basic expert consensus statements were developed in a workshop on the 38th Annual Meeting of the German-speaking Community for Microsurgery of the Peripheral Nerves and Vessels (DAM).Statements were consented in regard of the aspects: timing of nerve and soft tissue repair, techniques of nerve repair, as well as rehabilitation and healing process control.


Trauma Und Berufskrankheit | 2016

Pseudarthrosen und komplikationsbehaftete Verläufe nach Mittelhandfrakturen

Leila Harhaus; Berthold Bickert; Ulrich Kneser

ZusammenfassungFrakturen der Mittelhandknochen verlaufen nicht selten komplikationsbehaftet und zeigen einen durch Delayed Union oder Pseudarthrosenbildung verzögerten Heilungsverlauf. Einen klaren Behandlungsalgorithmus gibt es aktuell noch nicht. Wir empfehlen ein stufenartiges Vorgehen: Eine hyperthrophe instabile Pseudarthrose ist durch eine osteosynthetische Stabilisierung, ggf. ergänzt um eine Spongiosaplastik zu behandeln. Atrophe Pseudarthrosen erfordern ein komplexeres Vorgehen. Bei überschaubarer Größe des knöchernen Defektes und Vorliegen von guten Weichteilverhältnissen ist eine Spongiosaanlagerung, bei größeren knöchernen Defekten bei weiterhin suffizienten Weichteilverhältnissen ist die Transplantation eines kortikospongiösen Beckenkammspans mit überbrückender Plattenosteosynthese das adäquate Verfahren. Bei großen Defekten und kompromittierter Weichteilsituation besteht die Indikation für einen freien vaskularisierten Knochentransfer. Auch die Anwendung modernerer Verfahren wie BMP (bone morphogenic protein)-Anlagerung oder supportive Behandlung mit niedrigenergetischem Ultraschall oder extrakorporaler Stoßwellentherapie sind denkbar. Aufgrund vieler moderner Therapieansätze ist eine aktuelle Evaluation dieser Thematik jedoch unabdingbar.AbstractIt is not uncommon for fractures of the metacarpal bones to develop complications and they are therefore at risk of developing a delayed union or pseudarthrosis which delay the course of healing. Currently, no clear treatment algorithm is existing. We recommend a stepwise approach: hypertrophic, an unstable pseudarthrosis should be treated by osteosynthetic stabilization and if necessary supplemented by spongioplasty. An atrophic pseudarthrosis requires a more complex strategy. A manageable size of bony defect in the presence of sufficient perfusion of surrounding soft tissue can be treated by cancellous bone transplantation or in the case of larger bony defects and a sufficient soft tissue situation with a corticocancellous graft from the iliac crest in combination with a bridging plate osteosynthesis. Large bony defects with poorly perfused surrounding soft tissue require a free vascularized bony and cutaneous tissue transfer. The use of modern approaches, such as administration of bone morphogenic protein (BMP) or treatment with extracorporeal shock wave therapy or low energy ultrasound therapy also have to be considered. Due to the many modern therapeutic approaches, a current evaluation of this topic is, however, inevitable.


Injury-international Journal of The Care of The Injured | 2016

Microsurgical reconstruction for post—traumatic defects of lower leg in the elderly: A comparative study

Lingyun Xiong; Emre Gazyakan; Matthias Wähmann; Amir K. Bigdeli; Thomas Kremer; Leila Harhaus; Jiaming Sun; Ulrich Kneser; Christoph Hirche

BACKGROUND Lower leg microsurgical reconstruction in the elderly is challenging, especially for post - traumatic defects. The present study aimed to evaluate the risk factors, management and outcome of free tissue transfer in patients older than 65 years of post-traumatic defects. METHODS Retrospective chart review was performed for all patients older than 18 years undergoing free tissue transfer for post-traumatic lower leg reconstruction from April 2000 to November 2014. A comparative study was designed to identify risk factors and outcome. RESULTS In total, 197 patients (ages 18-64) and 44 patients (ages ≥65, average 71.7±6.3) were included and allocated into cohort 1 and 2, respectively. Cohort 2 had a higher rate of diabetes mellitus and/or peripheral artery disease (46.6%, P<0.01). There was no significant difference in major flap complications, donor site complications and amputation rates (P>0.05). A higher rate of intensive care unit (ICU) admission was observed in cohort 2 (37.8%, P<0.01). Comparable limb salvage rates were recorded (97.1% and 95.6%, P=0.59) with an average follow-up of 25.9±30.1months in cohort 1 and 23.7±16.6months in cohort 2. CONCLUSION Post-traumatic microsurgical free tissue transfer to the lower leg can be performed safely in patients older than 65 years with high success rate and manageable complications.

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