Jurij Kiefer

Multiple extracorporeal shock wave therapy degrades capsular fibrosis after insertion of silicone implants.

Capsular fibrosis is the most frequent long-term complication after insertion of silicone devices. Today, mainly direct immunostimulation and subclinical infection are held responsible for inducing and maintaining inflammatory reactions, which lead to overwhelming extracellular matrix formation. Extracorporeal shock waves (ESWs) are capable of inhibiting inflammatory processes and revealing antibacterial capacity. In our previous study, we observed decelerated capsule development after application of a single shock wave immediately after surgery. The purpose of this study was to evaluate the effects of multiple ESWT after insertion of silicone implants in the same rodent model. Therefore, silicone prostheses were inserted into a submuscular pocket in 12 additional male Lewis rats, and shock waves were administered over a 14-d interval. At 35 d (n = 6) and 100 d (n = 6) after insertion, silicone implants and surrounding capsule tissue were removed and prepared for histologic and immunohistochemical analysis, as well as polymerase chain reaction (Ccl2, CD68, transforming growth factor β1, matrix metalloproteinase 2). Compared with the control group, multiple ESWT had no effect on day 35, but resulted in a significantly thinner capsule on day 100 (825.8 ± 313.2 vs. 813.3 ± 47.9, p = 0.759, and 1062.3 ± 151.9 vs. 495.4 ± 220.4, p < 0.001, respectively). The capsule was even thinner than after a single shock wave application, which had been found to result in thinner capsules at every time point in our previous study. This active degradation of the fibrous envelope caused by multiple ESWs was accompanied by synergistic alterations in pro- and anti-fibrotic proteins (transforming growth factor β1 and matrix metalloproteinase 2, respectively). In conclusion, after insertion of silicone devices, single ESWT is capable of decelerating capsule formation in contrast to multiple ESWT, which degrades fibrotic tissue. These findings seem to be associated with inhibition of inflammation and beneficial effects on pro- and anti-fibrotic proteins.

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.

An Integrative Therapeutic Concept for Surgical Treatment of Severe Cases of Lymphedema of the Lower Extremity

BackgroundLymphedema results from insufficient lymphatic drainage and typically affects the extremities. Recent studies revealed obesity as another cause of extremity lymphedema. Conservative treatment of patients with elephantiastic lymphedema of the lower extremity is limited and often inadequate. Resecting surgery plays an important role in these cases. Here, we investigated the effects of an integrated therapy concept on outcome and complication rates.MethodsWe retrospectively analyzed the clinical outcome of 26 patients with elephantiastic lymphedema of the lower limb who underwent a complex decongestive physical therapy (CDP) perioperatively and reduction surgery in our clinic between 1998 and 2011. We subsequently compared these patients (group A) with a control group of 30 patients (group B) who received medial thigh lift due to post-bariatric or aesthetic issues between 2011 and 2013. The incidence of complications, reoperations, blood transfusion, and duration of hospital stay was analyzed. All patients in group A received CDP perioperatively in a specialized lymphological clinic.ResultsBoth groups are comparable in terms of age and sex. Patients significantly differ in terms of BMI (p < 0.001). Thirty-six reductive procedures were performed in group A and 30 in group B. We did not see any significant difference in the incidence of complications (p = 1.000) and the rate of postoperative blood transfusions (p = 0.116).ConclusionsWe were able to show that an integrative concept including surgery is a good additional option for the treatment of severe cases of lymphedema in appropriate candidates. Furthermore, an adequate perioperative conservative setting helps to minimize possible complications.

In view of standardization Part 2: Management of challenges in the initial treatment of burn patients in Burn Centers in Germany, Austria and Switzerland

INTRODUCTION Initial therapy of severe burns in specialized burn trauma centers is a challenging task faced by the treating multi-professional and interdisciplinary team. A lack of consistent operating procedures and varying structural conditions was recently demonstrated in preliminary data of our group. These results raised the question on how specific treatment measures in acute burn care are met in the absence of standardized guidelines. MATERIAL AND METHODS A specific questionnaire containing 57 multiple-choice questions was sent to all 22 major burn centers in Germany, Austria and Switzerland. The survey included standards of airway management and ventilation, fluid management and circulation, body temperature monitoring and management, topical burn wound treatment and a microbiological surveillance. Additionally, the distribution of standardized course systems was covered. RESULTS 17 out of 22 questionnaires (77%) were returned completed. Regarding volume resuscitation, results showed a similar approach in estimating initial fluid while discrepancies persisted in the use of colloidal fluid and human albumin. Elective tracheostomy and the need for bronchoscopy with suspected inhalation injury were the most controversial issues revealed by the survey. Topical treatment of burned body surface also followed different principles regarding the use of synthetic epidermal skin substitutes or enzymatic wound debridement. Less discrepancy was found in basic diagnostic measures, body temperature management, estimation of the extent of burns and microbiological surveillance. CONCLUSION While many burn-related issues are clearly not questionable and managed in a similar way in most participating facilities, we were able to show that the most contentious issues in burn trauma management involve initial volume resuscitation, management of inhalation trauma and topical burn wound treatment. Further research is required to address these topics and evaluate a potential superiority of a regime in order to increase the level of evidence.

Domestic bioethanol-fireplaces–a new source of severe burn accidents

BACKGROUND Bioethanol-fueled fireplaces are popular interior home decoration accessories. Although their safety is promoted frequently, actual presentations of severe burn injuries in our burn intensive care unit (ICU) have focused the authors on safety problems with these devices. In this article we want to explore the mechanisms for these accidents and state our experiences with this increasingly relevant risk for severe burn injuries. MATERIALS AND METHODS The computerized medical records of all burn intensive care patients in our burn unit between 2000 and 2014 were studied. Since 2010, 12 patients with bioethanol associated burn injuries were identified. Their data was compared to the values of all patients, except the ones injured by bioethanol fireplaces that presented themselves to our burn ICU between the years 2010 and 2014. RESULTS At time of admission the bioethanol patients had a mean ABSI-score of 4.8 (+/- 2.2 standard deviation (SD)). A mean of 17 percent (+/- 9.1 SD) body surface area was burned. Involvement of face and hands was very common. An operative treatment was needed in 8 cases. A median of 20 days of hospitalization (range 3-121) and a median of 4.5 days on the ICU (range 1-64) were necessary. No patient died. In most cases the injuries happened while refilling or while starting the fire, even though safety instructions were followed. In the control group, consisting of 748 patients, the mean ABSI-score was 5.6 (+/- 2.7 SD). A mean of 16.5 percent (+/- 10.1 SD) body surface area was burned. Treatment required a median of 3 days on the burn ICU (range 1-120). Regarding these parameters, the burden of disease was comparable in both groups. CONCLUSION Bioethanol-fueled fireplaces for interior home decoration are a potential source for severe burn accidents even by intended use.

Comparison of symmetry after smile reconstruction for flaccid facial paralysis with combined fascia lata grafts and functional gracilis transfer for static suspension or gracilis transfer alone

Facial paralysis has a profound impact on functionality and esthetics of the oral region. In patients with strong skin laxity and soft tissue ptosis, functional smile reconstruction is challenging due to the accentuated asymmetry at rest. Thus, the purpose of the study was to analyze facial symmetry in this patient clientele following a combination of dynamic reanimation with fascial strips for static suspension compared to functional gracilis transfer alone.

Efficacy of a Gel Containing Polihexanide and Betaine in Deep Partial and Full Thickness Burns Requiring Split-thickness Skin Grafts: A Noncomparative Clinical Study

Despite overall advances in burn therapy, wound infection remains one of the leading causes of morbidity and mortality in patients with severe burn injuries. This prospective, multicenter, noncomparative clinical trial was conducted to assess the efficacy and safety of Prontosan® Wound Gel X (PWX), a gel containing polihexanide and betaine, for moistening and cleansing in deep tissue burn wounds requiring split-thickness skin grafting. Patients with deep partial or full thickness burn wounds requiring split-thickness skin grafting were treated with the gel to evaluate its tolerability and safety as well as graft take and the healing of the skin graft. Target wounds were assessed clinically and by using a photo-planimetric analyzing software for re-epithelialization. From 04/2012 to 05/2015, burn patients from three burn centers in Germany were screened for the study, of which 51 patients met the inclusion criteria. Predominantly deep partial thickness burn wounds were found (88.2 %). Except for one graft failure, all patients reached complete re-epithelialization after one (n = 14), two (n = 31), or three (n = 5) administrations of the gel. The median time to complete graft take was 7 days and was below the average healing time reported in comparable studies. No wound infection or erythema occurred. This is the first study to document the outcomes of deep partial and full thickness burns treated with PWX for moistening and cleansing. The gel was shown to be efficacious, safe, and well tolerated for use in burn wounds requiring split-thickness skin grafts.

Staged Hand Salvage and Reconstruction with Three Free Tissue Transfers: A Ten-year Follow-up

Health care systems in many countries are confronted with increasing economic limitations. Thus, complex microsurgical procedures and extensive rehabilitation programs are poorly compensated. However, this case demonstrates a dramatic reduction of socioeconomic expenses by allowing a potential radiocarpal amputee to return to work for another estimated 30 years.