Yannick Diehm

A Mobile Extracorporeal Extremity Salvage System for Replantation and Transplantation.

BackgroundTraumatic amputation is the second leading cause of limb loss in the United States. The preferred treatment is salvage and replantation of the amputated limb, whenever possible, and allotransplantation is a novel procedure whereby healthy limbs are procured from deceased organ donors and transplanted into the amputee recipient. A major restriction for both procedures is the irrecoverable muscle damage occurring due to ischemia. We investigated the feasibility of using a novel lightweight, mobile perfusion device specifically designed to perfuse amputated porcine limbs with an acellular perfusion solution to delay ischemic muscle damage prior to transplantation or replantation. MethodsBilateral hind limbs of Yorkshire pigs were amputated; one of the limbs was preserved by perfusion in the mobile perfusion device, and the other by storage in ice slurry for 12 hours. ResultsFive sets of bilateral limbs were preserved as described previously. A defined pressure of 30 mm Hg was reliably maintained in the arterial system without loss of flow. Comparison of the perfusate composition before and after limb passage revealed significant differences. Muscle biopsies showed a consistent progression of clusters of hypoxic cells in the control limbs with time. Similar changes could not be observed in the perfused tissue. ConclusionsWe have designed and built a small, mobile perfusion device that is operational and that more closely mimics the normal physiological environment when compared with the current standard of preservation in ice slurry. This project may have far-reaching implications for the treatment of limb loss through replantation and transplantation.

ADSCs in a fibrin matrix enhance nerve regeneration after epineural suturing in a rat model

Due to their unique properties, adipose derived stem cells (ADSCs) obtain promising potential to enhance nerve regeneration. The aim of this study was to investigate if fibrin‐glue embedded ADSCs were a beneficial adjunct to primary coaptation in a rat sciatic nerve model. Materials and methods: Fifty male Lewis rats underwent sciatic nerve transection and subsequent epineural suture repair. The treatment group received ADSCs re‐suspended in fibrin glue, while the control group received fibrin glue only. After 7, 21, 35, and 63 days, analysis involved axon count, myelin sheath thickness as well as N‐ and G‐ratios. Additionally, muscle weight quotient (operated vs. non‐operated site of the same animal) was calculated and compared between treatment and control groups. For co‐detection of vital ADSCs, vessel walls, and Schwann cells, immunolabeling was performed with CM‐DiI, SMA, and S‐100 antibodies, respectively. Results: ADSCs led to a significant increase of myelinization at day 21 (0.508 ± 0.085 μm vs. 0.381 ± 0.044 μm, P = 0.025) and day 35 (0.872 ± 0.09 µm vs. 0.495 ± 0.078 µm; P = 0.01) after surgery. Axon count was significantly increased at day 21 (420 ± 119 vs. 129 ± 63; P = 0.003) and day 63 (284 ± 137 vs. 111 ± 26; P = 0.046) after surgery. N‐ and G‐ratios were significantly different compared with control indicating enhanced nerve regeneration due to ADSC treatment at each time point (P < 0.05). Muscle weight quotient was significantly higher in the treatment group compared with the control at day 21 (44.01% ± 6.16% vs. 35.03% ± 2.61%; P = 0.014) and day 63 (65.49% ± 2.81% vs. 58.79% ± 4.06%; P = 0.009) after surgery. Co‐detection of immunolabeled cells showed vital ADSCs at the neuronal repair site and in close proximity to intraneuronal vessels indicating active participation of ADSCs in the process of nerve regeneration and associated angiogenesis. Conclusion: ADSCs embedded in a fibrin matrix can significantly enhance regeneration of peripheral nerve injuries after primary coaptation.

The Collagenase of the Bacterium Clostridium histolyticum for the Treatment of Capsular Fibrosis after Silicone Implants.

Background: The main part of the fibrotic capsule in capsular contracture is collagen. The collagenase of the bacterium Clostridium histolyticum is U.S. Food and Drug Administration approved for the treatment of Dupuytren contracture and might be capable of dissolving the fibrotic capsule surrounding silicone implants. Methods: One hundred twenty days after insertion of miniature silicone implants the authors performed in vitro studies (n = 14) for optimum dosage-finding and subsequent in vivo studies (n = 36) to evaluate application method and efficiency. Data analysis involved histologic measurements of capsule thickness and collagen density; 7-T magnetic resonance imaging–based in vivo imaging; and polymerase chain reaction analysis of inflammatory, profibrotic, and antifibrotic markers. Results: Compared with the control group, each dosage showed significantly thinner capsules after in vitro incubation. Skin digestion occurred in 0, 1 (7 percent), and 11 cases (80 percent) after incubation with 0.3, 0.9, and 1.8 mg/ml, respectively. In vivo application showed a dosage-dependent decrease in capsule formation, which was more prominent in lower capsule parts, seen by magnetic resonance imaging. In vivo skin perforation was seen in two (17 percent) and six cases (50 percent) after injection of 0.3 mg/ml and 0.9 mg/ml, respectively. Profibrotic and inflammatory markers were significantly up-regulated 10 days after collagenase injection. Conclusions: The collagenase of C. histolyticum is capable of dissolving the fibrotic capsule surrounding silicone implants. Skin perforation occurred most likely because of mechanical irritation after complete digestion of the capsule. Further studies are required to pave the way for safe clinical application.

Efficacy and Safety of the Collagenase of the Bacterium Clostridium Histolyticum for the Treatment of Capsular Contracture after Silicone Implants: Ex-Vivo Study on Human Tissue

Background The fibrotic capsule that surrounds silicone implants consists mainly of collagen. The FDA-approved collagenase of the bacterium clostridium histolyticum provides a reasonable treatment option. Safety and efficacy at the female breast site must be evaluated before clinical utilization. Materials and Methods We incubated 20 samples of fibrotic capsule as well as 12 full thickness skin grafts harvested from the female breast site for 24 hours with different doses of collagenase. Outcome measures involved histological assessment of thickness and density of the capsule tissue as well as the skin grafts. Furthermore, we performed a collagen assay and immunohistochemistry staining for collagen subtypes. Results Collagenase treatment was able to degrade human capsule contracture tissue ex-vivo. The remaining collagen subtype after degradation was type 4 only. 0.3 mg/ml of collagenase was most effective in reducing capsule thickness when compared with higher concentrations. Of note, effectiveness was inversely related to capsule density, such that there was less reduction in thickness with higher capsule densities and vice versa. Furthermore, the application of 0.3mg/ml collagenase did not lead to thinning or perforation of full thickness skin grafts. Conclusion Adjustment of collagenase dose will depend on thickness and density of the contracted capsule. A concentration of 0.3mg/ml seems to be safe and effective in an ex-vivo setting. The remaining collagen subtype 4 is suitable to serve as a neo-capsule/acellular tissue matrix. Collagenase treatment for capsular contracture may soon become a clinical reality.

Silicone Implants with Smooth Surfaces Induce Thinner but Denser Fibrotic Capsules Compared to Those with Textured Surfaces in a Rodent Model

Purpose Capsular contracture is the most frequent long-term complication after implant-based breast reconstruction or augmentation. The aim of this study was to evaluate the impact of implant surface properties on fibrotic capsule formation in an animal model. Materials and Methods Twenty-four rats received 1 scaled down silicone implant each; 12 of the rats received implants with textured surfaces, and the other 12 received implants with smooth surfaces. After 60 and 120 days, rats in each group underwent 7-Tesla Magnetic Resonance Imaging (MRI) and high-resolution ultrasound (HR-US), and specimens of the capsules were acquired and used to measure capsule thickness through histology, collagen density through picro sirius red staining, and analyses of expression of pro-fibrotic and inflammatory genes (Collagen1-4, TGFb1, TGFb3, Smad3, IL4, IL10, IL13, CD68) through qRT-PCR. Furthermore, MRI data were processed to obtain capsule volume and implant surface area. Results On day 60, histology and HR-US showed that fibrotic capsules were significantly thicker in the textured implant group with respect to the smooth implant group (p<0.05). However, this difference did not persist on day 120 (p=0.56). Capsule thickness decreased significantly over the study period in both smooth and textured implant groups (p<0.05). Thickness measurements were substantiated by MRI analysis and volumes changed accordingly. Implant surface area did not vary between study dates, but it was different between implant types. On day 60, the density of collagen in the fibrotic capsules was significantly lower in the textured implant group with respect to the smooth group (p<0.05), but again this difference did not persist on day 120 (p=0.67). Collagen 1 and CD68 were respectively over- and under expressed in the textured implant group on day 60. Significant differences in the expression of other genes were not observed. Conclusion Silicone implants with textured surfaces led to temporarily thicker but less dense fibrotic capsules compared with smooth surfaces. 7-Tesla MRI and HR-US are capable for non-invasive in-vivo assessment of capsular fibrosis in an animal model and can provide unique insights into the fibrotic process by 3D reconstruction and surface area measurement.

Topische Externa zur Prävention und Therapie hypertropher Narben und Keloide: Eine Literaturrecherche

BACKGROUND The treatment and prevention of hypertrophic scars and keloids represents a special challenge particularly in plastic surgery. Given their simple, non-invasive and painless application, topical preparations are an attractive therapeutic option. On the part of the patients, the efficacy in prevention of and therapy for hypertrophic scars and keloids of these topical preparations is regularly questioned. The clarification of this issue is subject of this review. MATERIAL AND METHODS A systematic literature research on the databases Medline, Medline Plus, Oldmedline and Cochrane Library was conducted. All randomised controlled trials, meta-analyses, systematic reviews, case series and case studies from the German and English literature, dealing with topical preparations approved in the German speaking area, were included. RESULTS In this research, 14 topical preparations were identified. However, there is limited data regarding their efficacy as compared to each other, to other treatment options or untreated controls. Only for 6 topical preparations studies with high evidence level exist. Contractubex showed best results in the prevention of pathological scars. CONCLUSION Even though Contractubex shows preventive effects and can be recommended based on current data, further studies are needed to strengthen the body of evidence and to prove the therapeutic efficacy of topical preparations in general.

Software-based video analysis of functional outcomes of face transplantation

Assessment of outcomes after face transplantation (FT) is necessary to provide sound evidence on the benefits of this life‐giving surgery. Current methods for outcomes assessment, however, are imprecise or prone to subjectivity. Software‐based video analysis may allow fast, objective and retrospective assessment of restoration of facial movements and functions after FT.

Comparison of sub- versus suprafascially raised anterolateral thigh free flaps with regard to donor-site morbidity, function and aesthetics

Although the anterolateral thigh flap (ALT) is one of the most frequently applied free flaps in plastic surgery, it remains controversial if the flap should be raised in a sub‐ or suprafascial plane. The purpose of this study was to compare both harvest techniques regarding donor‐site morbidity and outcomes.

2529: Software based video analysis of functional outcomes of face transplantation

2529: Software based video analysis of functional outcomes of face transplantation Sebastian Fischer, MD, Nico Krezdorn, Anne Huang, Muayyad Alhefzi, Mario A. Aycart, Harriet Kiwanuka, Yannick Diehm, Thet S. Win, Ericka M. Bueno, and Bohdan Pomahac Brigham and Women’s Hospital, Boston, MA, USA Introduction Outcomes assessment in face transplantation is necessary to provide evidence in support of this livegiving surgery Current methods, however, are imprecise or prone to subjectivity Software-based video analysis allows for fast, objective and retrospective assessment of the functions related to facial movement and expression of emotions Patients and methods We recorded standard electronic videos of each of our 7 face transplant recipients before as well as every 3 to 6 months after transplantation Each video consists of a patient performing a standard sequence of facial movements We retrospectively analyzed all videos using a customized software (Affdex, iMotions, Boston, MA) that automatically tracks and measures the magnitude and direction of facial movements and expressions by recognizing 24 standard reference anatomical points in the face Subsequently, we compared the measurements obtained for a particular patient with those obtained for the same patient at different time points to assess facial motion recovery Results After a mean follow up of 35 years, every patient had showed significant improvements in facial motor function when compared with pre transplant time points Significant improvements were first observed after an average of 6 months after transplantation In 3 patients with partial face transplants, the extent and quality of motor function of the transplanted parts of the face did not show any significant differences compared to the unaffected part 1 y after transplantation Conclusion Software based video analysis provides the first assessment tool capable for objective, precise and reproducible analysis of facial motor and expressive function after face transplantation Of note, this software works with conventional camera and computer equipment, making widespread use possible Standardized lightning conditions and patients’ compliance with performing the facial motor tasks are required to achieve comparable results. CONTACT Bohdan Pomahac bpomahac@partners.org

Insufficient fibrinogen response following free flap surgery is associated with bleeding complications.

Background: Microvascular tissue transfer has become a safe and reliable tool in the reconstructive armamentarium, yielding high success rates. However, little is known about the changes in coagulation after free tissue transfer and their potential impact on morbidity. Methods: Fibrinogen concentration and platelet count among other values were available and assessed in 139 undergoing free tissue transfer before, immediately after, and 1–3 as well as 8–11 days after surgery. In patients undergoing urgent revision for either bleeding or microvascular thrombosis, blood samples were drawn directly before re-exploration. Results: In the patients without any surgical revision and in those with thrombosis of the microvascular pedicle, both fibrinogen concentration and platelet count increased significantly during the early and late post-operative window. Patients that developed bleeding necessitating re-exploration showed an inadequate increase in fibrinogen levels, resulting in significantly lower concentrations compared to the other two groups. There were no significant differences in platelet count or PTT between these groups. Conclusion: Free flap surgery induces acute and subacute changes in coagulation, comparable to other major surgeries and severe injuries. This leads to an increase in platelet count and fibrinogen over the post-operative course. Patients that developed bleeding requiring surgical re-exploration showed an insufficient increase in fibrinogen, resulting in significantly lower fibrinogen levels. Therefore, monitoring and correction of fibrinogen levels might aid in preventing or treating bleeding complications following free flap surgery.