[Scars from Nonsuicidal Self-Injury - What Plastic Surgery Can Do]. / Narben aus nichtsuizidalem selbstverletzendem Verhalten ­ therapeutische Möglichkeiten der plastischen Chirurgie.

Scars from Nonsuicidal Self-Injury - What Plastic Surgery Can Do Abstract. Objective: Nonsuicidal self-injury (NSSI) can induce characteristic scar patterns indicating the origin of these scars. This frequently results in the stigmatization of the involved patients with far-reaching consequences for their daily routine and quality of life. Despite patients being highly interested in scar correction, the potential of surgical therapy to alleviate NSSI-prone behavior and its help in destigmatizing surgical corrections and esthetic improvements in these situations are not well-known. Method: Over a period of 5 years, we analyzed 600 patients requesting NSSI scar treatment in our outpatient clinic. We collected data on the motivation for a scar correction, on the maturity of the scars, the involved body parts, and potential prior scar treatments as well as the amount, localization, and type of performed surgical procedures in our institution. Results: Stigmatization (57 %) and limitations in choice of clothing (18 %) were the most frequent reasons given for scar correction. We performed 358 dermabrasions and 55 serial excisions on these patients, nine combinations of both, and 13 other procedures. Conclusions: Plastic surgery offers multiple possibilities to reduce the stigmatization of patients with NSSI scars, who should thus be informed early about their choices.

[Non-suicidal self-injurious Behaviour: Insights into a littleknown Patient Population in Plastic Surgery]. / Nicht-suizidales selbstverletzendes Verhalten ­ Einblicke in ein wenig bekanntes plastisch-chirurgisches Patient*innenkollektiv.

BACKGROUND: Despite its high prevalence in adolescents and young adults, non-suicidal self-injury (NSSI) is poorly known and understood in areas other than psychiatry. Due to this lack of knowledge, affected patients often face a lack of understanding as well as rejection and discrimination when seeking help from medical professionals. This not only hampers a lasting improvement of NSSI and the development of a trustful physician-patient relationship but may also lead to traumatisation of affected patients. Based on our patients' data, this article aims to inform interested plastic surgeons about NSSI and thus to support the treatment of affected patients. PATIENTS AND METHODS: 600 patients with scars from NSSI presenting to our outpatient clinic for the first time during the past five years were enrolled in this study. Extensive data collected during the first contact was analysed and compared with the current literature. RESULTS: 95 % of the patients were female; 5 % were male. On average, patients presented 8.4 years after the last NSSI event and with a mean age of 26 years. NSSI scars were most often located on the left forearm (48 %), followed by both forearms (40 %), the left upper arm (20 %), both upper arms (15 %) and both thighs (14 %). In 57 % of patients, scars were only present on one side. A mean of 380 cm2 of the body surface was affected by NSSI scars. 47 % of patients reported having at least one additional diagnosis, with thyroid dysfunction and depression being the most common. 21 % of patients had ongoing psychiatric or psychological therapy at the time of their first consultation in our clinic. CONCLUSION: Our data provides first insight into a large population of NSSI patients seeking treatment options for their NSSI-associated scars in a plastic surgery outpatient clinic. Most patients were female with scars located on their forearms. A mean of more than 8 years had passed between their last NSSI and their first presentation to our clinic. Our findings offer a data-based approach to a group of patients with a disease pattern that is largely misunderstood in surgical disciplines and needs more attention, especially in the light of its high prevalence and life-long consequences.

In vivo cardiac pacemaker function of differentiated human mesenchymal stem cells from adipose tissue transplanted into porcine hearts.

BACKGROUND: Mesenchymal stem cells (MSC) modified by gene transfer to express cardiac pacemaker channels such as HCN2 or HCN4 were shown to elicit pacemaker function after intracardiac transplantation in experimental animal models. Human MSC derived from adipose tissue (haMSC) differentiate into cells with pacemaker properties in vitro, but little is known about their behavior after intracardiac transplantation. AIM: To investigate whether haMSC elicit biological pacemaker function in vivo after transplantation into pig hearts. METHODS: haMSC under native conditions (nhaMSC) or after pre-conditioning by medium differentiation (dhaMSC) (n = 6 pigs each, 5 × 106 cells/animal) were injected into the porcine left ventricular free wall. Animals receiving PBS injection served as controls (n = 6). Four weeks later, total atrioventricular (AV)-block was induced by radiofrequency catheter ablation, and electronic pacemaker devices were implanted for backup stimulation and heart rate monitoring. Ventricular rate and rhythm of pigs were evaluated during a follow-up of 15 d post ablation by 12-lead-ECG with heart rate assessment, 24-h continuous rate monitoring recorded by electronic pacemaker, assessment of escape recovery time, and pharmacological challenge to address catecholaminergic rate response. Finally, hearts were analyzed by histological and immunohistochemical investigations. RESULTS: In vivo transplantation of dhaMSC into the left ventricular free wall of pigs elicited spontaneous and regular rhythms that were pace-mapped to ventricular injection sites (mean heart rate 72.2 ± 3.6 bpm; n = 6) after experimental total AV block. Ventricular rhythms were stably detected over a 15-d period and were sensitive to catecholaminergic stimulation (mean maximum heart rate 131.0 ± 6.2 bpm; n = 6; P < 0.001). Pigs, which received nhaMSC or PBS presented significantly lower ventricular rates (mean heart rates 47.2 ± 2.5 bpm and 37.4 ± 3.2 bpm, respectively; n = 6 each; P < 0.001) and exhibited little sensitivity towards catecholaminergic stimulation (mean maximum heart rates 76.4 ± 3.1 bpm and 60.5 ± 3.1 bpm, respectively; n = 6 each; P < 0.05). Histological and immunohistochemical evaluation of hearts treated with dhaMSC revealed local clusters of transplanted cells at the injection sites that lacked macrophage or lymphocyte infiltrations or tumor formation. Intense fluorescence signals at these sites indicated membrane expression of HCN4 and other pacemaker-specific proteins involved in cardiac automaticity and impulse propagation. CONCLUSION: dhaMSC transplanted into pig left ventricles sustainably induced rate-responsive ventricular pacemaker activity after in vivo engraftment for four weeks. The data suggest that pre-conditioned MSC may further differentiate along a pacemaker-related lineage after myocardial integration and may establish superior pacemaker properties in vivo.

Pacemaker cell characteristics of differentiated and HCN4-transduced human mesenchymal stem cells.

AIMS: Cell-based biological pacemakers aim to overcome limitations and side effects of electronic pacemaker devices. We here developed and tested different approaches to achieve nodal-type differentiation using human adipose- and bone marrow-derived mesenchymal stem cells (haMSC, hbMSC). MAIN METHODS: haMSC and hbMSC were differentiated using customized protocols. Quantitative RT-PCR was applied for transcriptional pacemaker-gene profiling. Protein membrane expression was analyzed by immunocytochemistry. Pacemaker current (If) was studied in haMSC with and without lentiviral HCN4-transduction using patch clamp recordings. Functional characteristics were evaluated by co-culturing with neonatal rat ventricular myocytes (NRVM). KEY FINDINGS: Culture media-based differentiation for two weeks generated cells with abundant transcription of ion channel genes (Cav1.2, NCX1), transcription factors (TBX3, TBX18, SHOX2) and connexins (Cx31.9 and Cx45) characteristic for cardiac pacemaker tissue, but lack adequate HCN transcription. haMSC-derived cells revealed transcript levels, which were closer related to sinoatrial nodal cells than hbMSC-derived cells. To substitute for the lack of If, we performed lentiviral HCN4-transduction of haMSC resulting in stable If. Co-culturing with NRVM demonstrated that differentiated haMSC expressing HCN4 showed earlier onset of spontaneous contractions and higher beating regularity, synchrony and rate compared to co-cultures with non-HCN4-transduced haMSC or HCN4-transduced, non-differentiated haMSC. Confocal imaging indicated increased membrane expression of cardiac gap junctional proteins in differentiated haMSC. SIGNIFICANCE: By differentiation haMSC, rather than hbMSC attain properties favorable for cardiac pacemaking. In combination with lentiviral HCN4-transduction, a cellular phenotype was generated that sustainably controls and stabilizes rate in co-culture with NRVM.

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 ß1, 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 ß1 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.

Pulsed acoustic cellular expression (PACE) reduces capsule formation around silicone implants.

UNLABELLED: Capsular contracture remains a major complication after reconstructive or aesthetic breast augmentation. Formation of capsular fibrosis is a multifactorial process. An initial inflammatory reaction appears to be key to the development of capsular contracture. Recent studies have shown that pulsed acoustic cellular expression (PACE) has significant antiinflammatory effects. Thus, this study aimed to determine the potential of PACE to prevent or attenuate capsular contracture around silicone implants in a rodent model. For this study, 36 Lewis rats were divided into two groups, and a textured silicone implant was placed in a dorsal submuscular pocket. One group received PACE treatment, whereas the other group served as the control group and received no treatment. Follow-up evaluations were performed after 10, 35, and 100 days. Capsule thickness, collagen density, myofibroblasts, vascular density, and a semiquantitative real-time polymerase chain reaction that addressed differential gene expression were assessed. The PACE treatment significantly reduced capsule thickness on days 10, 35, and 100 compared with the control group (day 10: 632.9 ± 164.5 vs 932.6 ± 160.8, p < 0.05; day 35: 709.5 ± 175 vs 825.9 ± 313.3, p < 0.0.5; day 100: 736.3 ± 198.1 vs 1,062.3 ± 151.9, p < 0.05). This was accompanied by a significant suppression of proinflammatory genes (cluster of differentiation 68, monocyte chemotactic protein-1, CCL4) and synergistic alterations of pro- and antifibrotic proteins (transforming growth factor-beta 1, matrix metalloproteinase-2). This study showed that the PACE application significantly reduces capsular contracture around silicone implants. A decrease in capsular thickness after PACE treatment seems to be associated with a downregulation of proinflammatory genes and proteins. The study identifies PACE technology as a potential low-cost technique that is easy to use for reduction of capsular contracture after augmentation using silicone implants. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Bed isolation in experimental flap studies in rats: a dispensable procedure.

Review of the literature regarding rodent experimental flap models reveals fundamental differences in applied surgical procedures. Although some authors isolate the flap from its wound bed, others do not. This study was planned to investigate to what extent the insertion of a silicone sheet affects physiological wound healing in experimental flap surgery. An extended epigastric adipocutaneous flap (6 × 10 cm) was raised in 16 male Lewis rats. In the control group (group C), flaps were immediately inset without any intervention. In the experimental group (group M), a silicone sheet barrier was placed between the flap and the wound bed. Mean flap survival area and flap perfusion were evaluated. Microvessel density was visualized by immunohistochemistry, and semiquantitative real-time polymerase chain reaction addressed differential gene expression. All animals were investigated on postoperative day 5. Flap survival area and flap perfusion were found to be similar. Immunohistochemistry, however, demonstrated a significantly increased number of CD31-positive small vessels in group C. The insertion of the silicone sheet barrier (group M) was accompanied by a significantly enhanced expression of proinflammatory genes and a suppression of proangiogenic genes. Our results show that although the silicone membrane has no influence on the surgical outcome in terms of flap survival and perfusion, it does lead to significant molecular alterations in pathways involved in physiological wound healing. These alterations are artificially induced by the foreign body material and conceal the true driving forces of the healing process. As the latter might include relevant therapeutic targets to ameliorate surgical results, we regard wound bed isolation as a dispensable procedure in the study of rodent flap models.

Adipose derived stem cells protect skin flaps against ischemia-reperfusion injury.

BACKGROUND: Advances in the treatment of ischemia- reperfusion injury have created an opportunity for plastic surgeons to apply these treatments to flaps and implanted tissues. We examined the capability of adipose derived stem cells (ADSCs) to protect tissue against IRI using an extended inferior epigastric artery skin flap as a flap ischemia- reperfusion injury (IRI) model. METHODS: ADSCs were isolated from Lewis rats and cultured in vitro. Twenty- four rats were randomly divided into three groups. Group I was the sham group and did not undergo ischemic insult; rather, the flap was raised and immediately sutured back (non-ischemic control group). Group II (ischemia control) and group III (ADSCs treatment) underwent 3 h of ischemic insult. During reperfusion group III was treated by intravenous application of ADSCs and group II was left untreated. Five days postoperatively, flap survival and perfusion were assessed. Microvessel density was visualized by immunohistochemistry and semi- quantitative real-time polymerase chain reaction addressed differential gene expression. RESULTS: Treatment with ADSCs significantly increased flap survival (p<0.001) and flap perfusion (p<0.001) when compared to the control group II. Microvessel- density in ADSCs treated group was not significantly increased in any group. No significant differences showed the comparison of the experimental group III and the sham operated control group I. ADSCs treatment (Group III) was accompanied by a significantly enhanced expression of pro-angiogenic and pro-inflammatory genes. CONCLUSION: Overall, our study demonstrates that ADSCs treatment significantly enhances skin flap survival in the aftermath of ischemia to an extent that almost equals surgical results without ischemia. This effect is accompanied with a pronounced and significant angiogenic response and an improved blood perfusion.

Extracorporeal shock wave treatment protects skin flaps against ischemia-reperfusion injury.

Advances in the treatment of ischemia-reperfusion injury have created an opportunity for plastic surgeons to apply these treatments to flaps and implanted tissues. Using an extended inferior epigastric artery skin flap as a flap ischemia-reperfusion injury (IRI) model, we examined the capability of extracorporeal shock wave treatment (ESWT) to protect tissue against IRI in a rat flap model. Twenty-four rats were used and randomly divided into three groups (n=8 for each group). Group I was the sham group and did not undergo ischemic insult; rather, the flap was raised and immediately sutured back (non-ischemic control group). Group II (ischemia control) and Group III (ESWT) underwent 3h of ischemic insult. During reperfusion Group III was treated with ESWT and Group II was left untreated. Histological evaluation was made to investigate treatment induced tissue alterations. Survival areas were assessed at 5d postoperatively. Skin flap survival and perfusion improved significantly in the ischemic animals following ESWT (p<0.001, respectively). The tissue protecting effect of ESWT resulted in flap survival areas and perfusion data equal to non-ischemic, sham operated flaps. In line with the observation of better flap perfusion, tissue from ESWT-treated animals (Group III) revealed a significantly increased frequency of CD31-positive vessels compared to both the ischemic (Group II; p=0.003) and the non-ischemic, sham operated control (Group I; p<0.005) and an enhanced expression of pro-angiogenic genes. This was accompanied by a mild suppression of pro-inflammatory genes. Our study suggests that ESWT improves flap survival in IRI by promoting angiogenesis and inhibiting tissue inflammation. The study identifies ESWT as a low-cost and easy to use technique for surgical techniques that aim at reducing ischemia-reperfusion-induced tissue injury.