[Medial end clavicle fractures: alternative osteosynthesis and brief review of the literature]. / Mediale Klavikulafraktur: alternative Osteosynthese und kurze Literaturübersicht.

Medial end clavicle fractures are rare injuries and typically treated conservatively. In contrast, displaced fractures have a higher incidence of delayed healing or non-union and might benefit from operative treatment. Thus, assessments of the stability and fracture morphology are essential for selection of the optimal treatment procedure. This article describes the diagnostics and surgical treatment of a displaced extra-articular fracture of the clavicle with a small medial fragment using an anatomically preformed radius plate.

Significance of myeloperoxidase plasma levels as a predictor for cardiac resynchronization therapy response.

OBJECTIVES: This study aimed to determine if changes in myeloperoxidase (MPO) levels correlate with response to cardiac resynchronization therapy (CRT) and the potential role of MPO as a predictor of response to CRT. BACKGROUND: CRT is a well-established treatment option in chronic heart failure (CHF) with 50-80% of patients benefiting. Inflammation and oxidative stress play a key role in CHF pathophysiology. Previous studies have demonstrated increased levels of MPO in CHF patients, but the correlation with CRT response remains incompletely understood. METHODS: Fifty-three patients underwent CRT implantation. During follow-up, patients were divided into two groups, responders and non-responders to CRT, based on improved physical capacity and NYHA classification. Levels of MPO and NT-pro-brain-natriuretic-peptide (NT-proBNP) were determined prior to implantation, 30 and 90 days after. Physical capacity, including a 6-min walking-test, NYHA class, and LVEF were evaluated at baseline and during follow-up. RESULTS: Thirty-four patients (64%) responded to CRT, showing improved physical capacity and LVEF. All responders revealed a significant decrease of MPO levels (503.8 ng/ml vs. 188.4 ng/ml; p < 0.001). Non-responding patients did not show any significant changes in clinical parameters or MPO levels (119.6 ng/ml vs. 134.3 ng/ml; p = 0.672) during follow-up. At baseline, physical capacity and NYHA class, as well as MPO levels differed significantly between both groups (p < 0.001). A ROC analysis identified an MPO cut-off value for response to CRT of 242 ng/ml with a sensitivity of 93.5% and specificity of 71.4%. There was a strong correlation between MPO and improvement of LVEF (Spearman's rho: - 0.453; p = 0.005) and physical capacity (Spearman's rho: - 0.335; p = 0.042). CONCLUSIONS: Response to CRT and course of MPO levels correlate significantly. MPO levels differ between responders and non-responders prior to CRT, which may indicate an additional value of MPO as a predictor for CRT response. Further randomized studies are required to confirm our data in larger patient cohorts.

Electrical cardioversion of patients with implanted pacemaker or cardioverter-defibrillator: results of a survey of german centers and systematic review of the literature.

AIMS: A relevant number of patients presenting for electrical cardioversion carry a pacemaker (PM) or ICD. Case reports suggest a potential hazard of external cardioversion/defibrillation. The incidence of shock related device complications is unknown. No guidelines or recommendations by international medical societies for a cardioversion protocol of cardiovascular implantable electronic device (CIED) patients exist. We conducted a nationwide survey to gather real-world clinical data on the current clinical approach towards these patients during electrical cardioversion and to estimate the incidence of shock-related complications. METHODS AND RESULTS: Ninety hospitals with > 380 ECV in 2014 were identified from mandatory hospital quality reports and 60 were randomly selected. All centers were provided with a standardized questionnaire on the general proceedings and complications during electrical cardioversion of pacemaker, ICD and CRT patients (CIED patients). Thirty-two centers (53%) participated in the survey. In total, 16,554 ECV were reported (534 ± 314 per center). Biphasic cardioversion with a first shock energy of ≥ 150 J via adhesive patches in antero-posterior orientation was preferred by most centers (78%). Eleven percent (n = 1809) of pts were reported to carry a PM/ICD. The ECV protocol was heterogeneous among centers. Complications associated with electrical cardioversion were reported in 11/1809 patients (0.6%), all were transitory elevations of pacing thresholds. CONCLUSIONS: In this nationwide snapshot survey of cardioversion procedures in Germany, approximately 11% of patients presenting for elective electrical cardioversion were pacemaker or ICD carriers. Cardioversion protocols in these patients are heterogeneous throughout centers and mostly not in accordance with recommendation of the German Cardiac Society. Complications associated with external electrical cardioversion are rare. Controlled trials and large registries are necessary to provide evidence for future recommendations.

[Catheter ablation and the complications]. / Katheterablation und die Komplikationen.

Catheter ablation of atrial fibrillation has developed into a standard therapy and even in some cases as a first line therapy. This has resulted in a clear increase in the number of procedures in recent years. The published data from experienced centers indicate that the number of complications decreases with increasing experience; however, due to the parallel increase in the number of inexperienced centers, the average complication rate shows a tendency to increase. In the long term this necessitates a reliable quality assurance in order not to leave the choice of the "safe centers" up to the patient. Vascular complications are the most common, which in most cases have an uneventful course and do not necessitate further interventions. Particularly the incidence of ischemic stroke can be well-countered by strict control of periprocedural anticoagulation. The frequency of occurrence of phrenic nerve lesions, which are more common when selecting cryoenergy, can be reduced by stimulation of the phrenic nerve during ablation of the right pulmonary vein. The most feared complication of an atrioesophageal fistula is rare. No data for an effective avoidance of complications are available. A postprocedural therapy with proton pump inhibitors for 4-6 weeks, the intraprocedural measurement of esophageal temperature and reduction of the ablation energy on the posterior wall of the left atrium can possible help to reduce the frequency of complications.

[Assessment of REC (Reduction in Earning Capacity) after Thermal Trauma as Part of the Appraisal Process for Statutory Accident Insurance in Germany (Part 2): The New REC Form Developed by Ottomann and Hartmann in 2010]. / Die Einstufung der MdE nach thermischem Trauma im Rahmen der Begutachtung der gesetzlichen Unfallversicherung (Teil II): Der neue MdE Bogen nach Ottomann und Hartmann 2010.

The calculation of REC forms the basis of expert opinions for the purposes of making accident insurance assessments after an occupational accident or an accident suffered en route while travelling to or from the workplace. The estimation of REC is based on a procedure quoted in the 1995 "Jahrbuch der Versicherungsmedizin" (Yearbook of Insurance Medicine) using a form developed by Henkel von Donnersmarck and Hoerbrand. The overall estimation of damages resulting from the accident comprises 3 main components, namely the functional impairment, the assessment of local findings and the resulting somatic and vegetative complaints. The criteria for all 3 components are nevertheless imprecise and open to a great deal of interpretation on the part of the evaluator, leading to a highly variable and subjective overall assessment of REC. The new REC form includes a modified factor-based categorisation of the scar quality and the localisation, so that assessment can now be carried out in a differentiated manner. Visible, stigmatising areas such as the neck are provided with their own Q values. The pigmental and textural alterations describing the scar quality are now more precisely defined. Considering the complexity of the somatic and vegetative alterations, more precise (objective) assessments can now be derived. The new REC form increases the validity and transparency of post-thermal trauma REC assessments for the purposes of making statutory accident insurance assessments.

[The Assessment of REC after Thermal Trauma as Part of the Appraisal Process for Statutory Accident Insurance in Germany (Part 1): Low Validity of the REC Form Developed by Donnersmarck and Hörbrand]. / Die Einstufung der MdE nach thermischen Trauma im Rahmen der Begutachtung der gesetzlichen Unfallversicherung (Teil I): Geringe Validität des MdE Bogens nach Donnersmarck und Hörbrand.

The total REC (reduction in earning capacity) after a thermal trauma is usually assessed using an appraisal form for burns victims, initially developed by Hoerbrandt and von Donnersmarck (1995). The criteria for functional impairment, local findings and vegetative-somatic complaints are somewhat imprecise given the broad scope of interpretation which the evaluator can employ in making an appraisal. This means that the overall appraisal of REC is subjective on the part of the evaluator. In addition, one can only calculate an overall REC of at most 40% from local findings and vegetative-somatic symptoms, even in patients with extensive large area burns. Considering these points we investigated the dependency of the results on the evaluator as well as the limited validity of the appraisal form originally developed by Hörbrand and Donnersmark.

Fumaderm® in daily practice for psoriasis: dosing, efficacy and quality of life.

BACKGROUND: Patients with psoriasis suffer from chronic skin disease and impaired quality of life. With a prevalence of 1-3% of the population, psoriasis is one of the most common chronic inflammatory autoimmune diseases. Fumaric acid esters (Fumaderm(®)) are approved for the treatment of psoriasis in Germany, but regular Fumaderm therapy with six tablets per day is often limited due to adverse events. OBJECTIVES: This observational study recorded data on quality of life, treatment efficacy and drug dosing in patients suffering from psoriasis treated with Fumaderm under conditions of daily practice in 78 dermatological centres. PATIENTS AND METHODS: In this prospective, multicentre, noninterventional trial we included adult patients with severe plaque psoriasis under outpatient conditions receiving Fumaderm according to the current summary of product characteristics for systemic treatment of psoriasis. At baseline and after 3, 6 and 12 months the dosing regimen under daily conditions, Dermatology Life Quality Index (DLQI) and clinical efficacy with the Psoriasis Area and Severity Index (PASI) were documented. RESULTS: A total of 249 patients were included. The mean DLQI score at study entry was 9·95; the mean PASI was 16·8. The average treatment dose of Fumaderm was 2·8 tablets daily. More than 70% of patients were treated with one to three tablets daily and < 30% were treated with a dose ranging from four to six tablets daily. DLQI and PASI improved in the entire study population by 67·2% and 66·6%, respectively. Specifically, when analysing patients who started Fumaderm within 4 weeks before baseline the mean DLQI score decreased from 11·8 to 2·9 (75% reduction) and the mean PASI score from 19·84 to 7·35 after 12 months (63% improvement). CONCLUSIONS: This is the first field study analysing the use of Fumaderm and the improvement of quality of life in patients with psoriasis under daily outpatient conditions. The improvement of DLQI obtained with Fumaderm was comparable with the improvement observed in patients with psoriasis treated with modern biologics. Importantly, in most patients with good clinical response, the treatment dose was one to three tablets daily.

[The social background of male to female transsexuals]. / Der soziale Rahmen und Hintergrund von Mann-zu-Frau-Transsexualität.

Gender alignment surgery was introduced into German law in 1981. Judicial guidelines for the change of first names and gender were established and transsexuality was labelled as a psychosomatic and somatopsychic syndrome and disorder, thus opening the way for treatment to the social health-care under well-defined conditions requesting cross-dressing and hormone therapy as well as psychological counselling by 2 independent psychologists or psychiatrists. In a retrospective, chart-related survey of questionnaires on male to female transsexuals it was found that patients start to suspect being born into the wrong gender at the onset of puberty, it takes them however approximately 20 years to have gender alignment surgery. More than half the patients are single at this time, while the remaining group is married or divorced with equal rates. 68% regard themselves as heterosexual, 21% lesbian and 11% were undecided. About half the patients experienced support by their families for their decision. Despite numerous secondary corrections of the surgical alignment, patients were content with the result, although emotional acceptance of the desired result took about one year. In general plastic surgical gender alignment treatment was perceived as the major contribution to harmonise their phenotype with their identity.

Pirogow's Amputation: A Modification of the Operation Method.

Introduction. Pirogow's amputation at the ankle presents a valuable alternative to lower leg amputation for patients with the corresponding indications. Although this method offers the ability to stay mobile without the use of a prosthesis, it is rarely performed. This paper proposes a modification regarding the operation method of the Pirogow amputation. The results of the modified operation method on ten patients were objectified 12 months after the operation using a patient questionnaire (Ankle Score). Material and Methods. We modified the original method by rotating the calcaneus. To fix the calcaneus to the tibia, Kirschner wire and a 3/0 spongiosa tension screw as well as a Fixateur externe were used. Results. 70% of those questioned who were amputated following the modified Pirogow method indicated an excellent or very good result in total points whereas in the control group (original Pirogow's amputation) only 40% reported excellent or very good result. In addition, the level of pain experienced one year after the completed operation showed different results in favour of the group being operated with the modified way. Furthermore, patients in both groups showed differences in radiological results, postoperative leg length difference, and postoperative mobility. Conclusion. The modified Pirogow amputation presents a valuable alternative to the original amputation method for patients with the corresponding indications. The benefits are found in the significantly reduced pain, difference in reduced radiological complications, the increase in mobility without a prosthesis, and the reduction of postoperative leg length difference.

[Pirogow's amputation as an alternative to lower leg amputation?]. / Die Amputation nach Pirogow als Alternative zur Unterschenkelamputation?

Pirogow's amputation at the ankle presents a valuable alternative to lower leg amputation for patients with the corresponding indications. Although this method offers numerous advantages for the patient, such as the ability to stay mobile without the use of a prosthesis, it is rarely performed (0.1% of all lower limb amputations). The results of the operations on 20 patients were objectified 12 months after the operation using a patient questionnaire (Ankle Score), and these results were then compared to those of 20 patients who underwent lower leg amputation. Using a point system the criteria pain, functional and radiological assessment, difference in leg length, and mobility without prosthesis were recorded and evaluated. 65% of those questioned who were amputated following the Pirogow method indicated an excellent or very good result, in the control group 60% of those having undergone a lower leg amputation responded similarly, indicating an excellent or very good result.In 30% in the Pirogow group in contrast to 20% after lower leg amputation postoperative complications lead to a revision-operation. In patients suffering from diabetes or restricted perfusion of the lower extremity an amputation at the level of the ankle has to be considered critically keeping the necessity of a revision-operation in mind. However, if it can be carried out successfully, the benefits of Pirogow-amputation are found in the significantly reduced difference in leg length and the increase in mobility without prosthesis.

[Increased self-confidence and decreased sexual discomfort after subpectoral mammaplasty]. / Gesteigertes Selbstvertrauen und vermindertes körperlich-sexuelles Missempfinden nach subpektoraler Mammaaugmentation.

INTRODUCTION: The study objectively discusses the causal relationship between submuscular breast augmentation mammaplasty and improved aspects of quality of life. The goal was to assess a possible increase in certain aspects after undergoing cosmetic breast enlargement surgery under consideration of 4 different aspects. MATERIALS AND METHODS: Between 2005 and 2006, a total of 65 women were given a standardised patient questionnaire (body image assessment questionnaire) preoperatively as well as 6 months postoperatively after undergoing cosmetic submuscular augmentation mammaplasty: 58 of these questionnaires could be evaluated successfully. All of the patients had undergone augmentation mammaplasty for the first time. The following criteria were assessed and evaluated using a point value system (0-100 points): attractiveness/self-confidence, insecurity/anxiety, emphasis placed on physical appearance, and sexual discomfort. RESULTS: With regard to the questions dealing with attractiveness/self-confidence, a highly significant improvement in the patient's self-assessment of said criteria after undergoing cosmetic submuscular augmentation mammaplasty as compared to their own preoperative assessment was apparent. In addition, a significantly improved level of sexual satisfaction after the medical procedure was also demonstrated. In the same fashion, the answers to the series of questions dealing with emphasis placed on physical appearance also exhibited a positive change. The only topic that exhibited next to no change was the series of questions dealing with insecurity/anxiety. CONCLUSION: Cosmetic augmentation mammaplasty is an available therapy that can increase a patient's own self-assessment of attractiveness and self-confidence in a significant way. In addition, this operation leads to a significant increase in sexual satisfaction, and because of this and the aforementioned change of emphasis placed on physical appearance, an overall improvement in certain aspects of the quality of life can be achieved.

The Alpha Project: a model system for systems biology research.

One goal of systems biology is to understand how genome-encoded parts interact to produce quantitative phenotypes. The Alpha Project is a medium-scale, interdisciplinary systems biology effort that aims to achieve this goal by understanding fundamental quantitative behaviours of a prototypic signal transduction pathway, the yeast pheromone response system from Saccharomyces cerevisiae. The Alpha Project distinguishes itself from many other systems biology projects by studying a tightly bounded and well-characterised system that is easily modified by genetic means, and by focusing on deep understanding of a discrete number of important and accessible quantitative behaviours. During the project, the authors have developed tools to measure the appropriate data and develop models at appropriate levels of detail to study a number of these quantitative behaviours. The authors have also developed transportable experimental tools and conceptual frameworks for understanding other signalling systems. In particular, the authors have begun to interpret system behaviours and their underlying molecular mechanisms through the lens of information transmission, a principal function of signalling systems. The Alpha Project demonstrates that interdisciplinary studies that identify key quantitative behaviours and measure important quantities, in the context of well-articulated abstractions of system function and appropriate analytical frameworks, can lead to deeper biological understanding. The authors' experience may provide a productive template for systems biology investigations of other cellular systems.

Feasibility and clinical applicability of polihexanide for treatment of second-degree burn wounds.

OBJECTIVES: Due to a partial rejection of mesh split-thickness skin grafts (mesh grafts) after application of povidone-iodine and silver nitrate and due to its better in vitro tolerance, polihexanide was investigated as an alternative and its applicability in the treatment of second-degree burn wounds. METHODS: In 4 patients with poorly healing decubitus ulcers the mesh grafts were each divided into three areas which were pre-treated with either undiluted povidone-iodine solution, 1% silver nitrate solution or 0.04% polihexanide solution. After 7 days of application the wound areas were compared clinically and histologically. Thereafter 14 patients (average extent of burns 28% TBSA) were treated in the same way. RESULTS: Clinically and histologically the mesh grafts treated with polihexanide showed by far the best re-epithelialization compared with the deep tissue necrosis and marked fibrin discharge observed for application of povidone-iodine and silver nitrate. The second-degree burn wounds treated with polihexanide epithelialized without any further débridement after an average of 10 days with remarkable freedom from pain. Compared with silver nitrate treatment, no fibrin film was observed on the wound. CONCLUSION: Polihexanide proved clinically and histologically superior to povidone-iodine and silver nitrate. For the treatment of second-degree burns, which cannot primarily be covered by plastic surgery, polihexanide is suitable because in addition to its antiseptic efficacy it does not inhibit the re-epithelialization process.

[Endoscopic brow lift with resorbable anchors]. / Die endoskopische Brauenanhebung mit resorbierbaren Hautankern.

The fixation of the galea to the skull presents one of the main impairments of endoscopic forehead lifts, which are still to be improved. A precise positioning, variation of force vectors and the ability to correct asymmetries are among the demands on this aesthetic procedure. Since the introduction of resorbable skin anchors, we have used them pairwise in 27 consecutive cases of endoscopic forehead lifts. In a retrospective study we found that the advantage of this system is primarily found in a reduction of operating time, ease and reliability of use and the possibility to individually adjust the direction and strength of tension after inserting the anchors into the skull. The disadvantage - apart from the high cost of the device - lies in the unreliable resorption time which, in all cases controlled, exceeded the 8-month period, proclaimed by the manufacturer. This made it necessary to surgically remove the anchors in 7 out of 27 patients. Consequently every patient is now informed about the possibility of a second intervention as early as 4 to 6 weeks postoperatively to remove the device.

Regulatory modules that generate biphasic signal response in biological systems.

Biochemical networks might be composed of modules. It is still not clear how biochemical modules can be defined and characterised. Here we propose a functional approach to module definition, considering different classes of biphasic regulation modules, which effect optimal cell response to intermediate signal strength. Each regulation class might possess unique properties that make it especially suitable for particular biological functions.

Priming of T cells with Ad-transduced DC followed by expansion with peptide-pulsed DC significantly enhances the induction of tumor-specific CD8+ T cells: implications for an efficient vaccination strategy.

In recent years, vaccination strategies using antigen-presenting cells (APC) have been under investigation. Antigen delivery using genetic immunization through ex vivo transduction of dendritic cells (DC) is supposed to enhance the induction of antitumor responses in humans by activating a broad range of peptide-specific CD8+ T cells. In this study, we compared the potential of adenoviral (Ad)-transduced versus peptide-pulsed DC to induce melanoma-antigen (Ag)-specific T-cell responses in vitro. Whereas gp100-peptide-pulsed DC induced long-lasting specific CD8+ T-cell responses against single peptides, Ad-transduced DC induced broad and strong, specific immunity against various peptides of the gp100-Ag. Surprisingly, several restimulations led to decreasing gp100-specific and in parallel to increasing anti-adenoviral T-cell responses. Nevertheless, those anti-adenoviral T-cell responses provided an "adjuvant" effect by inducing an early release of high amounts of IL-2/IFN-gamma, therewith enhancing CTL induction in the initiation phase. Based on these data, we suggest a prime/boost vaccination strategy in melanoma patients--combining the use of Ad-DC and peptide-pulsed DC--to obtain efficient and long-term antitumor T-cell responses.

Genetic immunization with a melanocytic self-antigen linked to foreign helper sequences breaks tolerance and induces autoimmunity and tumor immunity.

Mechanisms maintaining peripheral tolerance to self-antigens present a major obstacle for the development of antigen-specific melanoma vaccines, presumably because self-antigens are not able to stimulate a CD4 T-helper response. Using the melanosomal enzyme tyrosinase-related protein 2 (TRP2) expressed by melanocytes and most melanoma cells as a model self-antigen, we investigated whether linkage with a foreign immunogenic protein providing strong CD4 helper sequences would be able to circumvent tolerance and enhance the induction of antigen-specific tumor immunity. We found that genetic immunization of mice with cDNA encoding a fusion protein between enhanced green fluorescent protein (EGFP) from jellyfish and autologous murine TRP2 (EGFP.mTRP2) resulted in the stimulation of TRP2-reactive T cells in vivo. Importantly, immunization with EGFP.mTRP2 effectively protected mice against metastatic growth of B16 melanoma in the lungs and was associated with fur depigmentation as a sign of autoimmune-mediated destruction of melanocytes. Our results show that tumor vaccines consisting of self-antigens linked to immunogenic helper sequences can be successfully applied to the immunotherapy of melanoma and provide a scientific basis for the translation of this strategy in future clinical investigations.

Depletion of CD25(+) CD4(+) T cells and treatment with tyrosinase-related protein 2-transduced dendritic cells enhance the interferon alpha-induced, CD8(+) T-cell-dependent immune defense of B16 melanoma.

Transduction of B16 melanoma cells with IFN alpha (B16-IFN alpha) enhances CD8(+) T-cell-dependent tumor immunity in mice, resulting in delayed outgrowth in vivo. Here we provide evidence that CD4(+) T cells down-regulate the IFN alpha-induced tumor immune defense. Importantly, depletion of regulatory CD25(+) CD4(+) T cells prevented growth of B16-IFN alpha in most mice and promoted long-lasting protective tumor immunity. Rejection of B16-IFN alpha could also be achieved with therapeutic injections of dendritic cells genetically engineered to express the melanoma antigen tyrosinase-related protein 2. These results support the development of novel strategies for the immunotherapy of melanoma using IFN alpha in combination with elimination of regulatory T cells or antigen-specific immunization.

Adenovirus-transduced dendritic cells stimulate cellular immunity to melanoma via a CD4(+) T cell-dependent mechanism.

We previously showed that genetic immunization of C57BL/6 mice with recombinant adenovirus encoding human TRP2 (Ad-hTRP2) was able to circumvent tolerance and induce cellular and humoral immune responses to murine TRP2 associated with protection against metastatic growth of B16 melanoma. In the present study we compared delivery of Ad-hTRP2 with cultured dendritic cells (DC) and direct injections of Ad-hTRP2. We show that application of Ad-hTRP2 with cultured DC enhanced protective immunity to B16 melanoma cells. Most importantly, delivery of recombinant adenovirus with DC alters the character of the immune response resulting in preferential stimulation of strong cellular immunity in the absence of significant humoral immunity to the encoded antigen. Adoptive transfer of lymphocytes from mice immunized with Ad-hTRP2-transduced DC confirmed that cellular components of the immune response were responsible for rejection of B16 melanoma. The protective efficacy of Ad-hTRP2-transduced DC clearly depended on the presence of CD4(+) T helper cells. Furthermore, AD-hTRP2-transduced DC, but not direct injection of Ad-hTRP2, were effective in the presence of neutralizing anti-adenoviral antibodies. These preclinical studies demonstrate the superiority of melanoma vaccines consisting of cultured DC transduced with recombinant adenoviruses encoding melanoma antigens.