Allogeneic donor split skin grafts for treatment of refractory ulcers in cutaneous chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation-a retrospective analysis on seven patients.

Refractory skin ulcers due to severe chronic graft-versus-host disease (cGVHD) remain to be associated with significant morbidity and mortality.We performed an allogeneic donor skin transplantation in seven adult patients after allogeneic hematopoietic stem cell transplantation for cGVHD-associated refractory skin ulcers. While four patients received a split skin graft (SSG), in one patient, a full thickness skin graft for two small refractory ulcers of the ankle was performed, and one patient received in vitro expanded donor keratinocyte grafts derived from hair roots of the original unrelated donor. In one additional patient, a large deep fascial defect of the lower leg was covered with an autologous greater omentum free graft before coverage with an allogeneic SSG. An additional patient was treated with an autologous scrotal skin graft for a refractory ulcer associated with deep sclerosis of cGVHD after unrelated donor transplantation.All skin grafts engrafted and resulted in permanent coverage of the grafted ulcers without any signs of immunological mediated damage. In the patient receiving in vitro expanded keratinocyte grafts, two localized ulcers were permanently covered by donor skin while this approach failed to cover extensive circular ulcers of the lower legs.Allogeneic donor skin grafts are a valuable treatment option in refractory ulcers due to cGVHD but are restricted mainly to related donors while keratinocyte grafts from unrelated donors remain experimental. In male patients lacking a related donor, autologous scrotal skin graft may be an alternative option.

Postoperative monitoring of local and free flaps with contrast-enhanced ultrasound (CEUS)--analysis of 112 patients.

PURPOSE: Tissue defects are a common problem in trauma surgery and oncology. Flap transplantation is often the only therapy to cover such defects. Several monitoring systems are currently available but none has made it to the clinical routine. The aim of this study was to assess perfusion disturbances of local and free flaps using contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: 112 patients were examined during the first 72 hours after operation. CEUS was performed by one experienced examiner with a linear transducer (6 - 9 MHz, LOGIQE9/GE) after a bolus injection of 2.4 ml sulfohexa-fluoride microbubbles (SonoVue®, Bracco, Italy). Retrospective vascular perfusion was quantified by evaluating the stored DICOM cine loops using the perfusion software QONTRAST® (Bracco, Italy). Over a total penetration depth of 3 cm, every centimeter was analyzed separately. 27 complications were observed. Complete flap loss was only seen in 4 cases, while 23 flaps had to undergo minor revision and survived. RESULTS: Regarding the complete flap size, quantitative analysis showed significantly higher perfusion values in patients without complications compared to patients with complications: PEAK 16.5 vs. 10.0 (p = 0.001), TTP 32.6 vs. 22.2 (p = 0.001), RBV: 738.8 vs. 246.2 (p < 0.001), RBF 17.5 vs. 10.1 (p < 0.001) and MTT 43.1 vs. 29.5 (p = 0.001). Analysis of the correlation of the different flap types, age, sex and etiology of the tissue defect to the complication rate showed no statistical correlation. CONCLUSION: CEUS was capable of detecting vascular disturbances after flap transplantation. TTP, RBV and MTT seem to be the most accurately parameters and are not susceptible to malfunction during measurement.

Quantitative assessment of bone microvascularization after osteocutaneous flap transplantation using contrast-enhanced ultrasound (CEUS).

BACKGROUND: Extensive wound defects frequently have to be covered by free flap transplantation. A monitoring device for measuring capillary level perfusion of bone is currently not available. OBJECTIVE: The aim of the study was to detect complications after osteocutaneous flap transplantation using contrast-enhanced ultrasound (CEUS). Additionally quantitative analysis was performed by special perfusion software (QONTRAST®; Bracco, Italy). METHODS: 22 patients were examined after osteocutaneous flap transplantation during the first 72 h after operation. CEUS was performed with a linear transducer (6-9 MHz, LOGIQ E9/GE) after bolus injections of 2.4 ml ultrasound contrast agent (SonoVue®; Bracco, Italy). The osseous perfusion and soft tissue perfusion were analyzed separately and quantitative perfusion analysis was performed. Five patients had to undergo reoperation due to compromised flap microvascularization. RESULTS: In all 5 complications reduced osseous and soft tissue perfusion was seen using CEUS. Additionally using the perfusion parameters TTP (time to PEAK), RBV (regional blood volume), RBF (regional blood flow) und MTT (mean transit time), significantly lower soft tissue and osseous perfusion was detected. CONCLUSION: CEUS seems to be capable of detecting vascular disturbances and of assessing microvascularization of the osseous component after osteocutaneous flap transplantation.

A favorable donor site in microsurgery: Nerve and vein graft harvest from the dorsum of the foot.

BACKGROUND AND OBJECTIVES: In complex hand traumas nerves and vessels are often destructed without the possibility for primary repair. For bridging defects of nerves, veins and arteries grafts are necessary. Commonly nerve and vein grafts from adjacent donor sites as the wrist, forearm or cubital region are harvested. METHODS: This study is a retrospective cohort study. Between 2017 and 2019, 10 patients with complex hand injuries were treated. There were 8 males and 2 females, with an average age of 39 years (range 8-63 years). In all cases grafts were used of the dorsum of the foot for reconstructing of the severed digital nerves and arteries. All donor sites could be closed primarily. RESULTS: In 100% of cases nerves and veins of the dorsum of the foot showed a good size match as well as adequate length for a sufficient repair. The overall Hand Injury Severity Score (HISS) was determined with a median of 86 (range 57 to 286). In the area of the donor site no relevant complications were seen. CONCLUSIONS: In complex hand injuries the dorsum of the foot is a favorable donor site for nerve and vein graft harvest.

Post-mortem distribution of Iodinated Contrast Media (ICM) (iodixanol versus iopromide) in the porcine kidney after multiple bolus injections in vivo into the supra-renal aorta1.

 Iodinated contrast media (ICM) are widely used for diagnostic and interventional procedures in radiology and cardiology. Ideally, they should not interact with blood cells or vascular wall cells to avoid deteriorations of the blood circulation. However, it is well known that ICM can affect erythrocytes as well as endothelial cells which consequently might perturb especially the microcirculation. In former studies the influence of two ICM (iodixanol versus iopromide) on the vascular system, the development of blood stasis, on changes in renal resistive index (RRI) and vascular diameters, and on the post-mortem distribution of iodine as marker for ICM in the explanted kidneys was examined. The modus of ICM application into the supra-renal aorta followed the regime in interventional cardiology, so that 10 bolus injections were administered at steady intervals (iopromide 4,32 ml / iodixanol 5 ml) accompanied by infusion of 500 ml isotonic NaCl-solution.In the present study, the post-mortem X-ray analysis revealed that there were no differences in iodine content in the regions of the mid-cortex and the medullo-pelvic transition zone of the kidneys after application of both ICM. Remarkable differences, however, were found in the region of the capsule-near cortex, where the application of iopromide led to a significantly lower iodine content in the microcirculation. This is in good agreement with former studies, in which a maldistribution in this area, presumably due to a decrease in arteriolar inflow as a result of stasis/occlusion was shown.

Augmented reality of indocyanine green fluorescence in simplified lymphovenous anastomosis in lymphatic surgery.

BACKGROUND: A physiological and minimal invasive form of surgery with minimal risk to treat lymphedemas is the so-called supermicrosurgical lymphovenous anastomosis (LVA) where a lymph vessel is connected with a venule. METHODS: 30 patients (between 2018 and 2019) with secondary upper extremity lymphedema refractory to conservative therapy (manual lymph drainage and compression therapy were operated using the "simplified lymphovenous anastomosis" method). For the assessment of lymphatic supermicrosurgery, an operating microscope in which a near-infrared illumination system is integrated (Leica M530 OHX with glow technology ULT530, Leica Microsystems) and the IC-FlowTM Imaging System(Diagnostic Green)/Visionsense System (Medtronic) together with a ZEISS S8 microscope was used. Augmented reality intraoperative indocyanin green (ICG) lymphography-navigated modified "simplified lymphovenous anastomosis" were performed on the Leica microscope. All patients were informed about Off-label-use of ICG lymphography. RESULTS: 57 LVAs were performed with modified "simplified lymphovenous anastomosis" lymphography-guidance on 30 upper extremities. All patients showed good patency after lymphovenous anastomosis. CONCLUSIONS: Supermicrosurgery in the case of LVA is minimally invasive, highly effective, and shows a very low complication rate. The surgeon/equipment-related factors restrict the pratice of LVA, and its effectiveness limited by technical constraints.

Effect of iodinated contrast media on the oxygen tension in the renal cortico-medullary region of pigs.

Repeated injections of iodinated contrast media (CM) can lead to a deterioration of the renal blood flow, can redistribute blood from the renal cortex to other parts of the kidney and can cause small decreases of the blood flow in cortical capillaries, a significant reduction in blood flow in peritubular capillaries and a significant reduction in blood flow in the vasa recta. Therefore, a study in pigs was designed, to show whether the repeated injection of CM boli, alone, can cause a reduction of oxygenation in the cortico-medullar renal tissue - the region with the highest oxygen demand in the kidney - of pigs.While the mean pO2-value had only decreased by 0.3 mmHg from 29.9±4.3 mmHg to 29.6±4.3 mmHg (p = 0.8799) after the tenth Iodixanol bolus, it decreased by 5.9 mmHg from 34.0±4.3 mmHg to 28.1±4.3 mmHg after the tenth Iopromide bolus (p = 0.044). This revealed a remarkable difference in the influence of these CM on the oxygen partial pressure in the kidney.Repeated applications of CM had a significant influence on the renal oxygen partial pressure. In line with earlier studies showing a redistribution of blood from the cortex to other renal areas, this study revealed that Iodixanol - in contrast to Iopromide - induced no changes in the pO2 in the cortico-medullar region which confirms that Iodixanol did not hinder the flow of blood through the renal micro-vessels. These results are in favor of a hypothesis from Brezis that a microcirculatory disorder might be the basis for the development of CI-AKI.

Evaluation of the vascular integrity of free flaps based on microcirculation imaging techniques.

BACKGROUND: A free-flap graft refers to the free transfer of tissue to cover tissue defects caused by trauma or malperfusion in plastic surgery. The basic principle, which makes a free flap working is an adequate blood flow. We applied new techniques which are able to detect the blood flow of the anastomosis and of dermal and subdermal tissue layers in a reliable way. METHODS: To this end we applied innovative Ultrasound-techniques (contrast enhanced high resolution Ultrasound (US), color coded Doppler sonography (CCDS), Cross Beamtrade mark, Power Doppler, Tissue Harmonic Imagingtrade mark (THI), Speckle Reduction Imagingtrade mark (SRI)), as well as the Indocyanine Green (ICG) fluorescence angiography to evaluate the vascular integrity of 15 parascapular flaps implanted to the fore foot over a period of four years. The age of the subjects ranged from 16 to 60 years. The US machine (GE Logiq 9) was equipped with a Logiq 9L transducer (6-9 MHz) and the modalities of CHI (Contrast Harmonic Imaging) and True Agent Detection (dual view of B-Mode and contrast mode). RESULTS: The borders of the investigated flaps could be best detected using Cross Beamtrade mark Technology with SRItrade mark and THItrade mark. Power Doppler was able to detect anastomotic vessels even if they were twisted or elongated. Reduced perfusion curves were seen in cases with low anastomotic flow in CCDS. The CHItrade mark allowed dynamic flow detection of the microcirculation of the tissue graft over a depth of up to 3 cm including quantitative perfusion curves of tissue microcirculation by using TICtrade mark analysis. There is a strong correlation between the perfusion indices measured by ICG fluorescence angiography and CHItrade mark. Furthermore the ICG showed a remarkable enhancement of fluorescence in the flap borders, which need to be explored in future investigations. CONCLUSION: These new applications provide useful and effective methods for improved postoperative monitoring of free flaps in plastic surgery and can lead to substantial reduction in the overall risk of flap failure.

Contrast harmonic ultrasound and indocyanine-green fluorescence video angiography for evaluation of dermal and subdermal microcirculation in free parascapular flaps.

PURPOSE: Contrast harmonic ultrasound (CHI) with a linear transducer is a new diagnostic approach that allows dynamic and quantitative flow detection of tissue perfusion in microsurgery. The aim of the study was the evaluation of perfusion of the dermal and subdermal layers of microvascular tissue transplants with CHI in comparison to ICG-fluorescence angiography. MATERIAL AND METHOD: In a prospective clinical study Indocyanine-Green Fluorescence Video Angiography and Contrast Enhanced High Resolution Ultrasound (5-10 MHz; linear transducer; Logiq 9; GE) were used for evaluation of the microcirculation in 10 transplanted free parascapular flaps. Two regions were analysed, the centre of the flap and the region of the anastomosis. The perfusion patterns of both methods were compared. RESULTS: The perfusion indexes measured by ICG-fluorescence angiography correlated very precisely in all patients with the quantitative perfusion curves of contrast-enhanced US with CHI. Two flaps with slow filling and low dye intensity showed low contrast enhancement in CHI with modified perfusion curves with slow increase. In two cases a reduced perfusion and filling were found. There were no statistical differences between the two diagnostic methods (p>0.01). CONCLUSION: CHI improves US detections of dermal and subdermal microcirculation in comparison to ICG fluorescence angiography. CHI is a new diagnostic method for postoperative monitoring of free flaps.

Contrast harmonic ultrasound and indocyanine-green fluorescence video angiography for evaluation of dermal and subdermal microcirculation in free parascapular flaps.

PURPOSE: Contrast harmonic ultrasound (CHI) with a linear transducer is a new diagnostic approach that allows dynamic and quantitative flow detection of tissue perfusion in microsurgery. The aim of the study was the evaluation of perfusion of the dermal and subdermal layers of microvascular tissue transplants with CHI in comparison to ICG-fluorescence angiography. MATERIAL AND METHOD: In a prospective clinical study indocyanine-green fluorescence video angiography and contrast enhanced high resolution ultrasound (5-10 MHz; linear transducer; Logiq 9; GE) were used for evaluation of the microcirculation in 10 transplanted free parascapular flaps. Two regions were analysed, the centre of the flap and the region of the anastomosis. The perfusion patterns of both methods were compared. RESULTS: The perfusion indexes measured by ICG-fluorescence angiography correlated very precisely in all patients with the quantitative perfusion curves of contrast-enhanced US with CHI. Two flaps with slow filling and low dye intensity showed low contrast enhancement in CHI with modified perfusion curves with slow increase. In two cases a reduced perfusion and filling were found. There were no statistical differences between the two diagnostic methods (p>0.01). CONCLUSION: CHI improves US detections of dermal and subdermal microcirculation in comparison to ICG fluorescence angiography. CHI is a new diagnostic method for postoperative monitoring of free flaps.

WITHDRAWN: The use of integrated indocyanine green fluorescence microscope camera for intraoperative lymphography of supermicrosurgery.

Ahead of Print article withdrawn by publisher.

Vasopressor support vs. liberal fluid administration in deep inferior epigastric perforator (DIEP) free flap breast reconstruction - a randomized controlled trial.

BACKGROUND: Perioperatively, patients' hemodynamics are modulated predominantly by intravenous fluid administration and vasoactive pharmacological support. Vasopressor agents are suspected to be detrimental on free flap survival by the cause of vasoconstriction of the pedicle with consecutive reduced overall flap perfusion and by aggravation of flap dissection. OBJECTIVE: A novel, standardized fluid restrictive perioperative hemodynamic management was assessed for its feasibility in clinical practice in free flap patients undergoing breast reconstruction. METHODS: Patients were randomized to two perioperative regimens with different fluid and vasopressor limits. The primary endpoint regarded flap survival. Secondary endpoints included surgery times, time of patient ambulation and length of hospital stay. RESULTS: There was one total flap failure with liberal fluid administration (LFA). No total or partial flap failure was noted in the fluid restrictive regimen with norepinephrine administration up to 0.04µg/kg/min (FRV). No delay regarding operation time (p = 0.217), patient mobilization (p = 0.550) or hospital discharge (p = 0.662) was registered in the FRV study subpopulation compared to LFA. CONCLUSIONS: The results of this prospective interventional trial could not detect any negative impact of vasopressors, neither for the primary endpoint of flap survival nor for the overall patient outcome. The fear of vasopressor associated flap complications has led to a traditional liberal fluid administration, which failed to demonstrate any benefits when compared to a fluid restrictive vasopressor strategy.

Influence of Ultrasound Microbubbles on kidney oxygen tension.

Ultrasound contrast agents (USCA) allows the dynamic detection of blood flow of both the macro and microvasculature. An obvious prerequisite for USCAs is the unhindered passage of clinically relevant dose levels through the microcirculation especially of the lungue, where they have to pass capillaries with diameters of around 4 µm. While smaller microbubbles rapidly passed through the microcirculation along with the red blood cells, larger microbubbles, however, were observed to coalesce and interrupt the blood flow. Whether this might influence the tissue oxygen tension is unclear up to now.To examine this question a bolus of 2.4 ml SonoVue™ was injected into the suprarenal aorta at a flow rate of 10 ml/s (a dosage usually applied in the clinic). The pO2 in the outer medulla of the kidney was continuously measured using a flexible pO2 microcatheter. In addition, the SonoVue™ injection and its passage through the renal vasculature were documented by the CEUS technology to assess whether the microbubbles passed the kidney.The study revealed that SonoVue™ induced no changes of the mean oxygen partial pressure in the outer medulla which confirms that these microbubbles on their way through the medullar capillaries did not hinder the co-flow of blood through the renal microvessels in a big animal model with a renal morphology and function comparable to human kidneys. These results demonstrate that the CEUS diagnostic itself did not influence the system to be examined which is a most important prerequisite for any diagnostic method.

Vascular malformations of upper and lower extremity - from radiological interventional therapy to surgical soft tissue reconstruction - an interdisciplinary treatment.

This article presents our experience in managing peripheral vascular malformations of upper and lower extremities over a 4-year period in a series of 46 patients of the Department of Plastic Surgery treated in the Interdisciplinary Center of Vascular Anomalies (ICVA) at the University of Regensburg. The patients presented vascular malformations of upper and lower extremity and were selected from our prospective vascular anomalies file archive from 2012 to 2016. During this period in the ICVA at University of Regensburg were performed more than 1400 radiological interventional treatments in patients with vascular malformations.The purpose of this retrospective study was to review combined embolotherapy, sclerotherapy (embolo/sclerotherapy), and surgical procedures (surgical excision and soft tissue reconstruction) to manage vascular malformations. Treatments were principally induced to reduce pain, daily physical limitations, social discomfort and recover tegument continuity after ulceration.The 46 patients were first examined with noninvasive radiological procedures. After diagnosis was posed, embolo/sclerotherapy, surgical procedures and clinically as well as radiological follow-ups were coordinated and established by the multidisciplinary team. All vascular malformations were categorized according to the classification approved at the April 2014 General Assembly of International Society for the Study of Vascular Anomalies (ISSVA) in Melbourne, Australia. Arteriovenous malformations (AVMs) were further classified following the Cho-Do and Schobinger classification.Embolo/sclerotherapy shows to be the most appropriate procedure in vascular malformations treatment. Nevertheless was found that in case of complications or lack of improvement as well as to improve functional or aesthetical results, a following partial or complete surgical excision and immediate soft tissue reconstruction seems to be the gold-standard treatment. In addition, the precise clinical and radiological diagnosis as well as an intensive postoperative patient care have a significant positive influence on the clinical outcome and patient satisfaction while decreasing morbidity and recurrence during early and late follow-up.Vascular malformations require a multidisciplinary approach and individual treatment after complex excision and indispensable reconstruction.

Contrast enhanced ultrasound (CEUS) - an unique monitoring technique to assess microvascularization after buried flap transplantation.

OBJECTIVE: Incidence of patients requiring complex soft tissue or osseous reconstruction has dramatically increased. However most of the monitoring systems have limitations in tissue penetration and are not able to detect microvascular complications after transplantation of so-called buried-flaps, that have no contact to the surface.Aim of the study was to assess contrast enhanced ultrasound (CEUS) as monitoring tool after buried flap transplantations. METHODS: 20 patients were examined after buried flap transplantation using CEUS. Quantitative perfusion analysis (TIC) was performed with an integrated perfusion software using stored cine-loops. Two perfusion-parameters, time to PEAK (TtoPk) and area under the curve (Area), were evaluated using TIC analysis. RESULTS: Minor complications were observed in 3 patients. In these patients a delayed contrast agent wash-in and wash-out was observed. Additionally the perfusion values TtoPk (sec.) and Area (relative Units) were clearly different in the patients with minor complications: TtoPk: 32.0 sec; Area 425.5 rU (without complication), TtoPk: 38.6 sec.; Area: 18.3 rU (wound healing disturbance) and TtoPk: 14.4 sec.; Area: 105.9 rU (hematoma). CONCLUSION: As CEUS can assess microvascularization almost depth-independent, CEUS is an unique method to assess global flap perfusion after buried flap transplantation.

Effect of radiographic contrast media on renal perfusion - First results.

BACKGROUND: Intra-arterial administration of radiographic contrast media (CM) is discussed to impair renal perfusion. The pathogenesis of contrast-induced Nephropathy (CIN) is still not clarified. OBJECTIVE: This trial was performed to prove the effects of two CM with different molecular structure on renal perfusion. METHODS: A prospective, randomized study on 16 pigs was designed to compare the outcome after application of a low-osmolar iodinated CM (770 mOsm/kg H2O - Group1) and an iso-osmolar iodinated CM (290 mOsm/kg H2o - Group2).Color Coded Doppler Sonography (LOGIQ E9, GE, Milwaukee, USA) was applied for measuring the Renal Resistive Index (RRI) before and after the first, fifth, and tenth bolus of CM. Statistics was performed using analysis of variance for repeated measurements with the Factor "CM". RESULTS: All flow spectra were documented free of artifacts and Peak Systolic Velocity (PSV), Enddiastolic Velocity (EDV) and RRI respectively could be calculated. Mean PSV in Group 1 led to a decrease while in Group 2 PSV showed a significant increase after CM (p = 0,042). The course of the mean EDV in both groups deferred accordingly (p = 0,033). Mean RRI over time significantly deferred in both groups (p = 0,001). It showed a biphasic course in Group 2 and a decrease over time in Group 2. CONCLUSION: While iso-osmolar CM induced an increase of PSV and EDV together with a decrease of RRI, low-osmolar CM could not show this effect or rather led to the opposite.

Quantitative Assessment of Free Flap Viability with CEUS Using an Integrated Perfusion Software.

PURPOSE: New treatment strategies in oncology and trauma surgery lead to an increasing demand for soft tissue reconstruction with free tissue transfer. In previous studies, CEUS was proven to detect early flap failure. The aim of this study was to detect and quantify vascular disturbances after free flap transplantation using a fast integrated perfusion software tool. MATERIAL AND METHODS: From 2011 to 2013, 33 patients were examined by one experienced radiologist using CEUS after a bolus injection of 1-2.4 ml of SonoVue(®). Flap perfusion was analysed qualitatively regarding contrast defects or delayed wash-in. Additionally, an integrated semi-quantitative analysis using time-intensity curve analysis (TIC) was performed. TIC analysis of the transplant was conducted on a centimetre-by-centimetre basis up to a penetration depth of 4 cm. The 2 perfusion parameters "Time to PEAK" and "Area under the Curve" were compared in patients without complications vs. patients with minor complications or complete flap loss to figure out significant differences. TtoPk is given in seconds (s) and Area is given in relative units (rU) Results: A regular postoperative process was observed in 26 (79%) patients. In contrast, 5 (15%) patients with partial superficial flap necrosis, 1 patient (3%) with complete flap loss and 1 patient (3%) with haematoma were observed. TtoPk revealed no significant differences, whereas Area revealed significantly lower perfusion values in the corresponding areas in patients with complications. The critical threshold for sufficient flap perfusion was set below 150 rU. CONCLUSION: In conclusion, CEUS is a mobile and cost-effective opportunity to quantify tissue perfusion and can even be used almost without any restrictions in multi-morbid patients with renal and hepatic failure.

Contrast enhanced ultrasound (CEUS) and time intensity curve (TIC) analysis in compartment syndrome: first results.

OBJECTIVE: Purpose of this study was to monitor changes of microcirculation in acute compartment syndrome using contrast enhanced ultrasound (CEUS) and to assess the modified perfusion with a special quantification software. METHODS: 8 patients with trauma of the lower limb or the upper extremity were enrolled after acute compartment syndrome was diagnosed clinically and by intracompartmental pressure measurement. The qualitative analysis of the corresponding compartment was assessed using B-scan mode and CEUS simultaneously. CEUS was performed using a multifrequence probe (6-9 MHz, LOGIQ E9 GE) after a i.v. bolus injection of 2 × 2.4 ml contrast agent (SonoVue(®), Bracco, Italy). Digital raw data were stored as cine loops up to 2 minutes. Retrospectively semiquantitative perfusion analysis was performed using time intensity curve analysis and the quantification software QONTRAST(®). RESULTS: 6 out of 8 patients had to be operated due to clinical symptoms and to a pressure perfusion gradient lower than 30 mm Hg. 2 out of 8 were treated conservatively. In all patients haematomas were seen in B-scan mode. No necrosis could be detected. In the TIC analysis low levels of time to peak (20.0 ± 12.1) and area under the curve (118.4 ± 87.8) were observed in acute compartment syndrome. Similarly results have been obtained using the perfusions parameter PEAK (11.1 ± 5.7), time to PEAK (14.7 ± 9.7), regional blood volume (257.1 ± 192.6), and regional blood flow (12.1 ± 6.5) in QONTRAST(®) perfusion software. CONCLUSION: CEUS may be capable of differing between acute compartment syndrome and imminent compartment syndrome.

Post-operative monitoring of tissue transfers: advantages using contrast enhanced ultrasound (CEUS) and contrast enhanced MRI (ceMRI) with dynamic perfusion analysis?

BACKGROUND: The immediate evaluation of microvascular tissue flaps with respect to microcirculation after transplantation is crucial for optimal monitoring and outcome. The purpose of our investigation was to evaluate the clinical value of contrast-enhanced ultrasound (CEUS) and contrast-enhanced MRI (ceMRI) for monitoring the integrity of tissue flaps in plastic surgery. METHODS: To this end, we investigated 10 patients (47 ± 16 a) between postoperative day 7 and 14 who underwent flap surgery in order to cover tissue defects in various body regions. For CEUS we utilized the GE LOGIQ E9 equipped with a linear transducer (6-9 MHz). After application of 2.4 ml SonoVue, the tissue perfusion was detected in Low MI-Technique (MI < 0.2). The perfusion curves were quantitatively analyzed using digital video sequences (QONTRAST, Bracco, Italy) regarding peak % and relative blood flow (RBF). Furthermore, we investigated all tissue flaps using contrast-enhanced MRI (Magnetom Symphony TIM, Siemens) with a 3D-VIBE sequence and a time resolution of 7s. Thus, the transplants were completely captured in all cases. As perfusion parameters, the positive enhancement integral (PEI) as well as the maximum intensity projection time (MIP-time) were collected. For comparison of both applications, all parameters were displayed in color-coded resolution and analyzed by three independent readers. Depending on the flap thickness, 1-3 regions of interest (ROI) were investigated. Each ROI measured 1 × 3 cm. RESULTS: The subcutaneous ROI-1 showed a significantly lower rating regarding RBF in the ceMRI compared to CEUS (Mann-Whitney Rank-Sum test, p < 0.05). ROI-2 and -3 did not show any significant differences between the two applications. The frequency distribution showed good accordance in both modalities. Both imaging techniques detected 1 partial flap necrosis within the random area of cutaneous and subcutaneous layers, 1 hematoma as well as 1 insufficient perfusion over all tissue layers. After subsequent reoperation, graft loss could be prevented. CONCLUSION: At present, both technologies provide an optimal assessment of perfusion in cutaneous, subcutaneous and muscle tissue layers, whereby the detection of fatty tissue perfusion is currently more easily detected using CEUS compared to ceMRI.

[Challenges in the organization of investigator initiated trials: in transplantation medicine]. / Herausforderungen in der Organisation "investigator initiated trials": Am Beispiel der Transplantationsmedizin.

INTRODUCTION: Transplantation medicine offers multiple translational questions which should preferably be transferred to clinical evidence. The current gold standard for testing such questions and hypotheses is by prospective randomized controlled trials (RCT). The trials should be performed independently from the medical industry to avoid conflicts of interests and to guarantee a strict scientific approach. A good model is an investigator initiated trial (IIT) in which academic institutions function as the sponsor and in which normally a scientific idea stands before marketing interests of a certain medical product. METHODS: We present a model for an IIT which is sponsored and coordinated by Regensburg University Hospital at 45 sites in 13 nations (SiLVER study), highlight special pitfalls of this study and offer alternatives to this approach. RESULTS: Finances: financial support in clinical trials can be obtained from the medical industry. Alternatively in Germany the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung) offers annual grants. The expansion of financial support through foundations is desirable. Infrastructure: sponsorship within the pharmaceutics act (Arzneimittelgesetz) demands excellent infrastructural conditions and a professional team to accomplish clinical, logistic, regulatory, legal and ethical challenges in a RCT. If a large trial has sufficient financial support certain tasks can be outsourced and delegated to contract research organizations, coordinating centers for clinical trials or partners in the medical industry. CONCLUSIONS: Clinical scientific advances to improve evidence are an enormous challenge when performed as an IIT. However, academic sponsors can perform (international) IITs when certain rules are followed and should be defined as the gold standard when scientific findings have to be established clinically.