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Various post-translationally modified (PTM) proteoforms of alpha-synuclein (aSyn)—including C-terminally truncated (CTT) and Serine 129 phosphorylated (Ser129-p) aSyn—accumulate in Lewy bodies (LBs) in different regions of the Parkinson's disease (PD) brain. Insight into the distribution of these proteoforms within LBs and subcellular compartments may aid in understanding the orchestration of Lewy pathology in PD. We applied epitope-specific antibodies against CTT and Ser129-p aSyn proteoforms and different aSyn domains in immunohistochemical multiple labelings on post-mortem brain tissue from PD patients and non-neurological, aged controls, which were scanned using high-resolution 3D multicolor confocal and stimulated emission depletion (STED) microscopy. Our multiple labeling setup highlighted a consistent onion skin-type 3D architecture in mature nigral LBs in which an intricate and structured-appearing framework of Ser129-p aSyn and cytoskeletal elements encapsulates a core enriched in CTT aSyn species. By label-free CARS microscopy we found that enrichments of proteins and lipids were mainly localized to the central portion of nigral aSyn-immunopositive (aSyn+) inclusions. Outside LBs, we observed that 122CTT aSyn+ punctae localized at mitochondrial membranes in the cytoplasm of neurons in PD and control brains, suggesting a physiological role for 122CTT aSyn outside of LBs. In contrast, very limited to no Ser129-p aSyn immunoreactivity was observed in brains of non-neurological controls, while the alignment of Ser129-p aSyn in a neuronal cytoplasmic network was characteristic for brains with (incidental) LB disease. Interestingly, Ser129-p aSyn+ network profiles were not only observed in neurons containing LBs but also in neurons without LBs particularly in donors at early disease stage, pointing towards a possible subcellular pathological phenotype preceding LB formation. Together, our high-resolution and 3D multicolor microscopy observations in the post-mortem human brain provide insights into potential mechanisms underlying a regulated LB morphogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Traumatic injuries of the triangular fibrocartilage complex (TFCC) are frequent reasons for ulnar wrist pain. The assessment of the extent of articular disc (AD) degeneration is important for the differentiation of acute injuries versus chronic lesions. Materials and methods: The AD of the TFCC of eleven human cadaver wrists was dissected. Degeneration was analyzed according to the grading of Krenn et al. Hematoxylin–eosin was used to determine the tissue morphology. Degeneration was evaluated using the staining intensity of alcian blue, the immunohistochemistry of the proteoglycan versican and the immunoreactivity of NITEGE, an aggrecan fragment. Results: The staining homogeneity of HE decreased with higher degeneration of the AD and basophilic tissue areas were more frequently seen. Two specimens were characterized as degeneration grade 1, five specimens as grade 2, and four specimens as grade 3, respectively. Staining intensity of alcian blue increased with higher degeneration grade of the specimens. Immunoreactivity for NITEGE was detected around tissue fissures and perforations as well as matrix splits. Immunoreactivity for versican was found concentrated in the tissue around matrix fissures and lesions as well as loose connective tissue at the ulnar border of the AD. Specimens with degeneration grade 2 had the strongest immunoreactivity of NITEGE and versican. Cell clusters were observed in specimens with degeneration grade 2 and 3, which were stained by alcian blue and immunoreactive for NITEGE and versican. Increasing age of the cadaver wrists correlated with a higher degree of degeneration (p < 0.0001, r = 0.68). Conclusions: The fibrocartilage of degenerated ADs contains NITEGE and versican. The amount of the immunoreactivity of these markers allows the differentiation of degenerative changes into three grades. The degeneration of the AD increases with age and emphasizes its important mechanical function. [ABSTRACT FROM AUTHOR]

Imaging the subsurface of the Earth is of prime concern in geosciences. In this scope, geophysics offers a wide range of methods that are able to produce models of the subsurface, classically through inversion processes. Deterministic inversions lack the ability to produce satisfactory quantifications of uncertainty, whereas stochastic inversions are often computationally demanding. In this paper, a new method to interpret geophysical data is proposed in order to produce 1D imaging of the subsurface along with the uncertainty on the associated parameters. This new approach called Bayesian Evidential Learning 1D imaging (BEL1D) relies on the constitution of statistics-based relationships between simulated data and associated model parameters. The method is applied to surface nuclear magnetic resonance for both a numerical example and field data. The obtained results are compared to the solutions provided by other approaches for the interpretation of these datasets, to demonstrate the robustness of BEL1D. Although this contribution demonstrates the framework for surface nuclear magnetic resonance geophysical data, it is not restricted to this type of data but can be applied to any 1D inverse problem. • A new approach for 1D imaging from geophysical data. • A set of MATLAB graphical user interfaces is provided. • Estimation of the uncertainty on the model parameters. • Consistent results for SNMR. • BEL1D can be generalized to any type of 1D geophysical data. [ABSTRACT FROM AUTHOR]

Background: With the increasing success of organ transplantation, many traditional contraindications to organ procurement are being reconsidered. Burn disease has constituted a traditional contraindication to solid organ procurement because of concerns that such organs may have been compromised by ischemia secondary to burn shock and contaminated by bacteremia. With the current shortage of solid organs, the transplant community continues to look for ways to increase the number of organ donors, including the use of marginal donors.Methods: Between 1999 and 2009 we have successfully procured 14 organs from four burn patients, who had suffered concurrent anoxic brain injury. There were one male and three female patients with an average age of 43.3 years and a total burned body surface area of 32.5%. Organ transplantation was performed at an average of 4.75days after the injury. Eight kidneys, three livers, two hearts and one pancreas were procured and transplanted into 13 patients.Results: We were able to follow-up on the organ recipients for an average of 80.5 months. The 5-year survival of the donated organs following transplant was 78.6% and the 5-year organ recipient survival was 92.3%.Conclusions: Organ procurement after burns is not contraindicated and transplantation can be performed with good long-term results. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Autologous postmastectomy breast reconstruction is associated with favourable long-term clinical outcomes and superior patient-reported outcomes (PROMs) compared with implant-based reconstruction. However, adjuvant radiotherapy has traditionally been considered a relative contraindication to immediate flap-based reconstruction due to its unpredictable effects on the reconstructive outcome. While modern adjuvant postmastectomy radiotherapy (PMRT) has been able to significantly reduce acute and chronic radiation-induced complications, plastic surgeons still hesitate to offer immediate autologous reconstruction to patients expected to undergo adjuvant radiotherapy. More recently, evidence has emerged suggesting a paradigm shift in favour of immediate autologous reconstruction despite subsequent radiotherapy. At the 44 th Annual Meeting of the German-speaking Society for Reconstructive Microsurgery (GSRM) in Bern, Switzerland, a workshop discussed the literature on PMRT and autologous breast reconstruction, aiming to establish consensus among the participants. Several areas of agreement were identified, including the goals of postmastectomy reconstruction, specifically the creation of a soft and sensitive breast symmetrical in shape and size to the unaffected breast via the safest procedure possible. The importance of preserving the maximum amount of native breast skin envelope through skin- and nipple-sparing approaches was emphasised. Finally, a consensus was reached that PMRT should no longer be considered a contraindication to immediate autologous breast reconstruction., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: The duration of the training for hand surgery in Germany was reduced from three to two years in 2020, while other European Countries introduced hand surgery as a separate surgical specialty. Therefore, the structure of hand surgery training in Germany is under intense, ongoing discussion., Objectives: This study aimed to evaluate the current situation of hand surgery training in Germany., Material and Methods: Two separate online questionnaires were developed for self-assessment of residents and teachers in German hand surgery services. The questionnaire contained 29 questions for residents and 24 questions for teachers. Demographic data, educational tools, surgical training parameters and satisfaction were assessed from May to July 2023. The survey was based on the former training time of three years. The online questionnaire was sent to the members and associate members of the German Society for Hand Surgery via email., Results: 148 participants answered the questionnaire, including 54 residents and 94 teachers. Overall, more female residents were assessed, whereas the majority of teachers was male. Hand surgery training is mostly conducted in high-level hospitals (tertiary care p=0.012, quaternary care p<0.001). Residents use digital teaching media significantly more often than teachers do (p<0.001). In contrast, teachers use journals (p=0.006) and clinical visits (p=0.024) significantly more often for their training than residents do. Trainers and trainees mostly agreed about time points of surgical milestones during surgical training that should be performed independently. Both trainers and trainees were largely satisfied with the practical and theoretical training in hand surgery., Conclusions: The importance of digital media in hand surgery training will increase in the near future. Therefore, digital media should be more frequently included in hand surgery training protocols. The study revealed that the majority of residents as well as teachers would appreciate the introduction of an independent hand surgery specialty, which would most likely improve the hand surgery competence in Germany., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Type-2 diabetes influences the course and severity of hand infections., Methods: We prospectively examined glucose metabolism in 90 patients with hand infection, distinguishing between normal, prediabetic and diabetic states. HbA1c-levels were evaluated prior to surgery. Patients with normal levels took an oral glucose tolerance test and those diagnosed with prediabetes were retested after the infection subsided. Hospital stay, number of surgical interventions and inflammatory markers were examined per group., Results: Sixty-two patients (68.8%) had abnormal glucose metabolism: 17 (18.9%) with history of diabetes and 11 (12.2%) newly diagnosed. Prediabetes was observed in 34 patients (37.8%). At follow-up, prediabetes and diabetes were diagnosed in 7 cases each, and physiological glucose metabolism was observed in 3 patients. For the 11 patients unable to undergo a second oral glucose tolerance test, detailed phone calls confirmed absence of diabetes. C-reactive protein levels were significantly elevated in diabetic patients compared to those with normal glucose metabolism (p = 0.001) or prediabetes (p = 0.034). Patients with history of diabetes were significantly older than those with normal glucose tolerance (p = 0.001) or prediabetes (p = 0.017). There were no significant intergroup differences in thrombocyte count, length of hospital stay, interval from injury to admission or the number surgical interventions., Conclusion: Glucose metabolism should be assessed in patients with hand infections and reassessed after the infection has subsided in prediabetic cases., (Copyright © 2024 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Background: Understanding the biological processes that underlie individual differences in emotion regulation and stress responsivity is a key challenge for translational neuroscience. The gene FKBP5 is a core regulator in molecular stress signaling that is implicated in the development of psychiatric disorders. However, it remains unclear how FKBP5 DNA methylation in peripheral blood is related to individual differences in measures of neural structure and function and their relevance to daily-life stress responsivity., Methods: Here, we characterized multimodal correlates of FKBP5 DNA methylation by combining epigenetic data with neuroimaging and ambulatory assessment in a sample of 395 healthy individuals., Results: First, we showed that FKBP5 demethylation as a psychiatric risk factor was related to an anxiety-associated reduction of gray matter volume in the ventromedial prefrontal cortex, a brain area that is involved in emotion regulation and mental health risk and resilience. This effect of epigenetic upregulation of FKBP5 on neuronal structure is more pronounced where FKBP5 is epigenetically downregulated at baseline. Leveraging 208 functional magnetic resonance imaging scans during a well-established emotion-processing task, we found that FKBP5 DNA methylation in peripheral blood was associated with functional differences in prefrontal-limbic circuits that modulate affective responsivity to daily stressors, which we measured using ecological momentary assessment in daily life., Conclusions: Overall, we demonstrated how FKBP5 contributes to interindividual differences in neural and real-life affect regulation via structural and functional changes in prefrontal-limbic brain circuits., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: The precise analysis of the injured structures requiring reconstruction in complex wound defects is a prerequisite for successful restoration., Objective: The fundamental reconstructive strategies for soft tissue defects of the extremities including injuries to vessels, nerves and burn wounds in the context of the acute and post-acute trauma phases are presented., Material and Methods: The different phases of soft tissue reconstruction are described. Recommendations for action with respect to the reconstruction of the functional structures are described. Two clinical case examples illustrate the approach., Results: The acute reconstruction phase is defined as the period 0-72 h after the traumatic event and includes surgical debridement, primary reconstruction of nerves and vessels using interpositional grafts if necessary and temporary soft tissue reconstruction. Combined thermomechanical trauma requires early debridement combined with internal fixation of open fractures. In the post-acute reconstruction phase, which is generally defined as a period of up to 6 weeks after the traumatic event, definitive soft tissue reconstruction is performed. In the case of long reinnervation distances, nerve transfer or motor replacement plastic surgery is performed in the post-acute phase., Conclusion: The reconstruction of soft tissue after trauma necessitates a stage-dependent approach. In the acute phase procedures aim at the immediate preservation of the limb. In the post-acute phase, definitive soft tissue reconstruction is performed to enable maximum functional preservation. Combined thermomechanical injuries require early surgical treatment in order to prevent infections., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: Sensory nerve endings transmit mechanical stimuli into afferent neural signals and form the basis of proprioception, giving rise to the self-perception of dynamic stability of joints. We aimed to analyze the three-dimensional structure of periarticular corpuscular sensory nerve endings in a carpal ligament to enhance our understanding of their microstructure., Methods: Two dorsal parts of the scapholunate ligament were excised from two human cadaveric wrist specimens. Consecutive cryosections were stained with immunofluorescence markers protein S100B, neurotrophin receptor p75, protein gene product 9.5 (PGP 9.5), and 4',6-diamidino-2-phenylindole. Three-dimensional images of sensory nerve endings were obtained using confocal laser scanning microscopy, and subsequent analysis was performed using Imaris software., Results: Ruffini endings were characterized by a PGP 9.5-positive central axon, with a median diameter of 4.63 μm and a median of 25 cells. The p75-positive capsule had a range in thickness of 0.94 μm and 15.5 μm, consisting of single to three layers of lamellar cells. Ruffini endings were significantly smaller in volume than Pacini corpuscles or Golgi-like endings. The latter contained a median of three intracorpuscular structures. Ruffini endings and Golgi-like endings presented a similar structural composition of their capsule and subscapular space. The central axon of Pacini corpuscles was surrounded by S100-positive cells forming the inner core which was significantly smaller than the outer core, which was immunoreactive for p75 and PGP 9.5., Conclusion: This study reports new data regarding the intricate outer and intracorpuscular three-dimensional morphology of periarticular sensory nerve endings, including the volume, number of cells, and structural composition. These results may form a basis to differ between normal and pathological morphological changes in periarticular sensory nerve endings in future studies., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

The treatment of burn injury patients is a unique challenge for clinicians. The extent of thermal injuries ranges from very small burns to life-threatening burn injuries. Insufficient treatment can result in a substantial impairment in the quality of life. In order to avoid such sequelae a targeted treatment must be carried out. A precise diagnosis determines the necessary treatment. Superficial second-degree burns (2a) not involving the face, hand or joints with a total body surface area smaller than 10% can usually be treated with modern wound dressings in an outpatient setting. Deep second-degree burns (2b) are an indication for debridement. In addition to the classical surgical procedures with tangential excision, enzymatic debridement can also be employed. Similarly, indeterminate burns (2a/2b) are also considered to be an indication for enzymatic debridement. Third-degree burns are treated with early debridement and skin grafting. These patients can also benefit from special dermal replacement procedures for an improvement of the functional and esthetic results. Due to the long-term visible sequelae of burns, aftercare of these patients is indicated., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: Heterozygous mutations within the voltage-gated sodium channel α subunit ( SCN1A ) are responsible for the majority of cases of Dravet syndrome (DS), a severe developmental and epileptic encephalopathy. Development of novel therapeutic approaches is mandatory in order to directly target the molecular consequences of the genetic defect. The aim of the present study was to investigate whether cis-acting long non-coding RNAs (lncRNAs) of SCN1A are expressed in brain specimens of children and adolescent with epilepsy as these molecules comprise possible targets for precision-based therapy approaches., Methods: We investigated SCN1A mRNA expression and expression of two SCN1A related antisense RNAs in brain tissues in different age groups of pediatric non-Dravet patients who underwent surgery for drug resistant epilepsy. The effect of different antisense oligonucleotides (ASOs) directed against SCN1A specific antisense RNAs on SCN1A expression was tested., Results: The SCN1A related antisense RNAs SCN1A -dsAS (downstream antisense, RefSeq identifier: NR&#95;110598) and SCN1A -usAS (upstream AS, SCN1A -AS, RefSeq identifier: NR&#95;110260) were widely expressed in the brain of pediatric patients. Expression patterns revealed a negative correlation of SCN1A-dsAS and a positive correlation of lncRNA SCN1A -usAS with SCN1A mRNA expression. Transfection of SK-N-AS cells with an ASO targeted against SCN1A -dsAS was associated with a significant enhancement of SCN1A mRNA expression and reduction in SCN1A -dsAS transcripts., Conclusion: These findings support the role of SCN1A -dsAS in the suppression of SCN1A mRNA generation. Considering the haploinsufficiency in genetic SCN1A related DS, SCN1A -dsAS is an interesting target candidate for the development of ASOs (AntagoNATs) based precision medicine therapeutic approaches aiming to enhance SCN1A expression in DS., Competing Interests: Conflict of interest: M.F.S., J.S., V.M., M.V., A.H.L.F., H.P., and I.Bor. received funding from Roche Ltd, Basel, Switzerland. T.K. and S.L. are employee at F. Hoffmann-La Roche Ltd, Basel, Switzerland. F.M. is a former employee of F. Hoffmann-La Roche Ltd, Basel, Switzerland. This does not alter our adherence to policies on sharing data and materials. All other authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Background: Nerve conduits are either used to bridge nerve gaps of up to 3 cm or to protect nerve coaptations. Biodegradable nerve conduits, which are currently commercially available, include Chitosan or collagen-based ones. As histological aspects of their degradation are highly relevant for the progress of neuronal regeneration, the aim of this study was to report the histopathological signs of such nerve conduits, which were removed during revision surgery., Materials and Methods: Either Chitosan (n = 2) or collagen (n = 2) nerve conduits were implanted after neuroma resection and nerve grafting (n = 2) or traumatic nerve lesion after cut (n = 1) or crush injury (n = 1) in two females and two men, aged between 17 and 57 years. Revision surgery with removal of the nerve conduits was indicated due to persisting neuropathic pain and sensorimotor deficits, limited joint motion, or neurolysis with hardware removal at a median time of 17 months (range: 5.5-48 months). Histopathological analyses of all removed nerve conduits were performed., Results: A scar neuroma was diagnosed in one out of four patients. Mechanical complication occurred in one patient after nerve conduit implantation bridged over finger joints. Intraoperatively no or only initial signs of degradation of the nerve conduits were observed. Chitosan conduits revealed largely unchanged shape and structure of chitosan, and coating of the conduit by a vascularized fibrous membrane. The latter contained deposits taken up by macrophages, most likely representing dissolved chitosan. Characteristic histopathologic features of the degradation of collagen conduits were a disintegration of the compact collagen into separate fine circular strands, No foreign body reaction was observed in all removed nerve conduits., Conclusions: Both Chitosan nerve conduits have not been degraded. The collagen nerve conduits showed a beginning degradation process. Furthermore, wrapping the repaired nerve with a nerve conduit did neither prevent adhesions nor improved nerve gliding. Therefore, biodegradation in time should be particularly addressed in further developments of nerve conduits., (© 2023 Wiley Periodicals LLC.)

Background: Giant cell tumors grow locally invasive with osseous and soft tissue destruction, requiring wide resection to avoid recurrence. Stable reconstruction of the first carpometacarpal (CMC-1) joint remains a challenge due to its high range of mobility. The latter is of paramount for the functionality of the hand., Purpose: Therefore, the aim of this study was to report our approach for a combined reconstruction of the first metacarpal and the CMC-1 joint., Methods: A 58-year-old woman underwent wide resection of a benign giant cell tumor at the base and shaft of the first metacarpal of the left thumb. Because of the loss of the CMC-1 joint and the instability of the thumb, an osseous reconstruction using a vascularized fibular graft combined with a TOUCH Dual Mobility CMC-1 prosthesis was performed to reconstruct the CMC-1 joint., Results: Osseous healing was observed after 3 months. No tumor recurrence and good joint function were documented at the follow-up investigation after 1 year. The patient reported only minor restrictions during activities of daily living. Thumb opposition was possible with a Kapandji score of 8/10. A slight pain while walking remained as a donor-side morbidity at the right lower leg., Conclusion: Metacarpal reconstruction with vascularized fibula bone grafts allowed a combined joint reconstruction with a commercially available prosthesis, which is an approach to restore the complex range of motion of the thumb., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The treatment of burn injury patients is a unique challenge for clinicians. The extent of thermal injuries ranges from very small burns to life-threatening burn injuries. Insufficient treatment can result in a substantial impairment in the quality of life. In order to avoid such sequelae a targeted treatment must be carried out. A precise diagnosis determines the necessary treatment. Superficial second-degree burns (2a) not involving the face, hand or joints with a total body surface area smaller than 10% can usually be treated with modern wound dressings in an outpatient setting. Deep second-degree burns (2b) are an indication for debridement. In addition to the classical surgical procedures with tangential excision, enzymatic debridement can also be employed. Similarly, indeterminate burns (2a/2b) are also considered to be an indication for enzymatic debridement. Third-degree burns are treated with early debridement and skin grafting. These patients can also benefit from special dermal replacement procedures for an improvement of the functional and esthetic results. Due to the long-term visible sequelae of burns, aftercare of these patients is indicated., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The Charlson Comorbidity Index (CCI) is used for the prognostic analysis of comorbidities. Comorbidities, especially diabetes mellitus, are a decisive factor for the development and course of hand infections. This study aimed to determine the CCI in patients with hand infections in order to examine how comorbidities influence the course and severity of hand infections., Material and Methods: Ninety patients with hand infections requiring surgery but without previous antibiotic treatment were studied prospectively. The respective CCI was determined on admission to hospital. A total score of zero points was defined as "low", a score of one to three as "medium" and a score of four to nine points as a "high" index. Age, CRP level, duration of inpatient stay and the number of performed surgeries were documented and statistically evaluated., Results: The median CCI was 0,5 points with a range of 0-9 points. The most common comorbidity was diabetes mellitus without end-organ damage, followed by heart failure and chronic lung disease. Patients with a low total score (median 51 years) were significantly younger than those with a medium score (median 60 years; p=0,018) or a high score (median 66,5 years; p=0,018). In addition, patients with a low or medium score had a shorter hospital stay (median 6 vs. 11,5 days; plow=0,003; pmean=0,005), required fewer surgeries (median 1 vs. 3 surgeries; plow=0,002; pmean=0,003) and had a lower CRP level (median 8,3 mg/l vs. 7,1 mg/l vs. 86,25 mg/l; plow=pmean=0,001) than those with a high index. A significant positive correlation was found between the CCI and patient age (Spearman's ρ=0,367; p<0,001) as well as the length of hospital stay (Spearman's ρ=0,261; p=0,013), the number of surgeries (Spearman's ρ=0,219; p=0,038) and the CRP level (Spearman's ρ=0,212; p=0,045)., Conclusions: The CCI is an appropriate questionnaire for the prognostic assessment of the course and severity of hand infections, particularly with regard to the length of hospital stay, the number of surgeries and the CRP level., Competing Interests: Susanne Rein: Firma Mediwound, und DIZG Berlin, aber nicht im Zusammenhang mit diesem Manuskript, sondern im Rahmen anderer Forschungsprojekte., (Thieme. All rights reserved.)

In addition to anaplastic large T-cell lymphomas (BIA-ALCL), other implant-related tumors have been described for some years. Squamous cell carcinoma (SSC) and B-cell lymphomas occurred in very rare cases. The unexplained pathogenesis as well as the unclear individual risk profile is an ongoing source of uncertainty for patients and physicians. The pathogenesis of the tumors is still largely not understood. While BIA-ALCL occurs more frequently with textured breast implants, other tumors were also observed with smooth implants and at other implant sites. Multiple potential mechanisms are discussed. It is suspected that the etiology of a chronic inflammatory response and subsequently immunostimulation is multifactorial and appears to play a key role in the malignant transformation. Since there are currently no sufficiently valid data for a specific risk assessment, this must be done with caution. This article presents the incidence, pathogenesis, as well as the level of evidence according to the current state of knowledge, and evaluates and discusses the current literature., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Large, full-thickness infrainguinal wounds following revision revascularization procedures of the lower extremity are a challenging complication for reconstructive surgery. Frequently, these patients present with various comorbidities and after several previous reconstructive attempts. Therefore no straightforward soft tissue reconstruction is likely., Methods: Patients who presented with large, complex inguinal wounds for soft tissue reconstruction were analyzed retrospectively in terms of flap choice, outcome, and complication rates. A focus was set on the reconstructive technique and a subgroup analysis was assessed., Results: Nineteen patients (11 men, 8 women) who received 19 flaps (17 pedicled, 2 free flaps) were included in this retrospective study. Average patient age was 73.3 years (range: 53-88). Ten fasciocutaneous flaps (anterolateral thigh [ALT], 52.6%) and 9 muscle flaps (47.4%) were applied. Among muscle flaps, 3 pedicled gracilis flaps, 4 pedicled rectus abdominis flaps, and 2 free latissimus dorsi flaps were used. No flap losses were observed except 1 case of limited distal flap necrosis (gracilis group). Body mass index ranged from 19 to 37, mean 26.8. Mean surgery time in all patients was 165.9 min (range: 105-373). Revision surgery due to local wound healing problems averaged 1.6 in all patients. In all cases sufficient soft tissue reconstruction was achieved and bypasses were preserved. Lengths of stay averaged 27.2 days (range: 14-59). Mortality was considerably (10.5%) due to systemic complications (one patient died due to a heart attack 4 weeks postoperatively, another patient died due to an extensive pulmonary embolism 2 weeks postoperatively)., Conclusions: Soft tissue reconstruction of complex inguinal wounds after revision vascular surgery is challenging and wound healing problems are expectable. In addition to the rectus abdominis flap the pedicled ALT flap is feasible in a broad variety of medium to large wounds. Free flap reconstruction is recommended for very large defects. A structured interdisciplinary approach is required for the management of complex wounds after vascular surgery to prevent and to deal with complications and perioperative morbidity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Early identification of risk for depression and anxiety disorders is important for prevention, but real-life affective well-being and its biological underpinnings in the population remain understudied. Here, we combined methods from epidemiology, psychology, ecological momentary assessment, and functional magnetic resonance imaging to study real-life and neural affective functions in individuals with subclinical anxiety and depression from a population-based cohort of young adults., Methods: We examined psychological measures, real-life affective valence, functional magnetic resonance imaging amygdala habituation to negative affective stimuli, and the relevance of neural readouts for daily-life affective function in 132 non-help-seeking community individuals. We compared psychological and ecological momentary assessment measures of 61 unmedicated individuals at clinical risk for depression and anxiety (operationalized as subthreshold depression and anxiety symptoms or a former mood or anxiety disorder) with those of 48 nonrisk individuals and 23 persons with a mood or anxiety disorder. We studied risk-associated functional magnetic resonance imaging signals in subsamples with balanced sociodemographic and image quality parameters (26 nonrisk, 26 at-risk persons)., Results: Compared with nonrisk persons, at-risk individuals showed significantly decreased real-life affective valence (p = .038), reduced amygdala habituation (familywise error-corrected p = .024, region of interest corrected), and an intermediate psychological risk profile. Amygdala habituation predicted real-life affective valence in control subjects but not in participants at risk (familywise error-corrected p = .005, region of interest corrected)., Conclusions: Our data suggest real-life and neural markers for affective alterations in unmedicated community individuals at risk for depression and anxiety and highlight the significance of amygdala habituation measures for the momentary affective experience in real-world environments., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Various studies have shown a decrease in well-being and an increase in mental health problems during the COVID-19 pandemic; however, only a few studies have explored fear, depression, and well-being cross-culturally during this time. Accordingly, we present the results of a cross-cultural study that (1) compares these mental health scores for German and South African students, (2) compares the correlations among them, and (3) identifies COVID-19 fear, well-being, and depression predictors. German and South African societies differ from each other socio-culturally, politically, and economically. Their university systems also differ to a large extent. University students in both countries completed the Fear of COVID-19 Scale, the World Health Organization-Five Well-Being Index (WHO-5), and the Patient Health Questionnaire-9 (PHQ-9). Welch's t -test, correlation, and multiple regression analyses were performed. (1) German students were found to have statistically lower levels of COVID-19 fear and depression, but lower levels of general well-being than South African students. (2) In both samples, fear of COVID-19 was negatively correlated with well-being and positively associated with female gender and depression. (3) Additionally, female gender, depression, and lower well-being were identified as predictors of COVID-19 fear in both samples. The findings indicate that the fear of COVID-19 is associated with and varies according to gender, depression, and well-being across cultures, and that the difference in the intensity of fear between German and South African students may be partly explained by cultural and contextual differences. These findings can create a deeper understanding of the pandemic's impact on student communities and may be used by mental health practitioners and researchers to develop and apply culture-specific interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Holm-Hadulla, Mayer, Wendler, Kremer, Kotera and Herpertz.)

This study aimed to compare the histomorphology of the elbow capsule and its ligaments to gain a better understanding of the clinically relevant biomechanical stabilization. Eleven human elbows were dissected including the joint capsule with its anterior (AJC) and posterior (PJC) parts, the annular ligament (AL), the radial collateral ligament (RCL) and the ulnar collateral ligament with its anterior (AUCL), posterior (PUCL) and transverse (TUCL) parts. Hematoxylin-Eosin and Elastica van Gieson as conventional histology stainings were applied to determine collagenous and elastic fiber arrangements in transmission and polarization light microscopy. The radial collateral ligament and the anterior part of the ulnar collateral ligament showed significantly more densely packed parallel fiber arrangement than the anterior joint capsule, the posterior joint capsule, and the posterior part of the ulnar collateral ligament (p < 0.02, respectively). The PUCL had significantly more mixed tight and loose parallel arrangements than the PJC, the annular ligament, the RCL, the AUCL and the transverse part of the ulnar collateral ligamentp < 0.02, respectively), while the PJC showed significantly more interlaced mixed tight and loose fiber arrangement than the AL, the RCL and the AUCL (p < 0.003, respectively). The AJC had a significantly higher amount of elastic fibers as compared to the AL, the RCL, the AUCL and the TUCL in fascicular regions (p < 0.04, respectively), while the AUCL had significantly lesser elastic fibers than the AJC and the PJC (p < 0.004, respectively). The densely packed parallel fiber arrangement and few elastic fibers of the AUCL, RCL, and AL indicate a strong biomechanically stabilizing function. The fiber arrangement of the PUCL and the TUCL with few elastic fibers support the medial elbow stabilization. Crimping and elastic fibers provide the viscoelasticity of the joint capsule., (© 2022 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Background: Soft tissue defects in the achilles tendon region occur after trauma, but also as a complication after open recon- struction of the tendon with subsequent infection., Objectives: Recommendations for the treatment of soft tissue injuries involving the Achilles tendon are presented., Materials and Methods: A search of the German, French and English literature on reconstruction of soft tissue defects of the Achilles tendon region was performed, which were differentiated into singular and combined tendocutaneous defects. Combined defects were further subdivided into three reconstructive principles: a simple soft tissue reconstruction without tendon repair or a combined reconstruction of the soft tissue as well as the tendon using either a vascularized tendon transplant or an avascular tendon graft., Results: Local and distally-based pedicled flaps include a relatively high risk or perioperative morbidity, whereas free flaps are described with significantly lower complications rates. Therefore, the authors prefer free flaps for reconstruction. Potential donor sites are the Medial Sural Artery (MSAP-) flap for smaller defects or free fasciocutaneous or muscle flaps in patients with large defects. The standard for tendocutaneousreconstructions is the free anterolateral thigh flap including vascularized fascia. Non-vascularized tendon grafts are frequently applied from the flexor hallucis longus- or peroneus brevis tendon., Conclusions: Reconstructions over the Achilles tendon require thin and stable reconstructions that additionally allow slippage of soft tissues. Moreover, the use of normal shoes should be possible. The postoperative strength and range of motion of the ankle joint show comparable functional results after vascularized and non-vascularized tendon reconstruction., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of neuronal E3 ligase UBE3A. Restoring UBE3A levels is a potential disease-modifying therapy for AS and has recently entered clinical trials. There is paucity of data regarding the molecular changes downstream of UBE3A hampering elucidation of disease therapeutics and biomarkers. Notably, UBE3A plays an important role in the nucleus but its targets have yet to be elucidated. Using proteomics, we assessed changes during postnatal cortical development in an AS mouse model. Pathway analysis revealed dysregulation of proteasomal and tRNA synthetase pathways at all postnatal brain developmental stages, while synaptic proteins were altered in adults. We confirmed pathway alterations in an adult AS rat model across multiple brain regions and highlighted region-specific differences. UBE3A reinstatement in AS model mice resulted in near complete and partial rescue of the proteome alterations in adolescence and adults, respectively, supporting the notion that restoration of UBE3A expression provides a promising therapeutic option. We show that the nuclear enriched transketolase (TKT), one of the most abundantly altered proteins, is a novel direct UBE3A substrate and is elevated in the neuronal nucleus of rat brains and human iPSC-derived neurons. Taken together, our study provides a comprehensive map of UBE3A-driven proteome remodeling in AS across development and species, and corroborates an early UBE3A reinstatement as a viable therapeutic option. To support future disease and biomarker research, we present an accessible large-scale multi-species proteomic resource for the AS community ( https://www.angelman-proteome-project.org/ )., (© 2022. The Author(s).)

Angelman syndrome (AS) is a severe neurodevelopmental disorder featuring ataxia, cognitive impairment, and drug-resistant epilepsy. AS is caused by mutations or deletion of the maternal copy of the paternally imprinted UBE3A gene, with current precision therapy approaches focusing on re-expression of UBE3A . Certain phenotypes, however, are difficult to rescue beyond early development. Notably, a cluster of microRNA binding sites was reported in the untranslated Ube3a1 transcript, including for miR-134, suggesting that AS may be associated with microRNA dysregulation. Here, we report levels of miR-134 and key targets are normal in the hippocampus of mice carrying a maternal deletion of Ube3a ( Ube3a m-/p+ ). Nevertheless, intracerebroventricular injection of an antimiR oligonucleotide inhibitor of miR-134 (Ant-134) reduced audiogenic seizure severity over multiple trials in 21- and 42-day-old AS mice. Interestingly, Ant-134 also improved distance traveled and center crossings of AS mice in the open-field test. Finally, we show that silencing miR-134 can upregulate targets of miR-134 in neurons differentiated from Angelman patient-derived induced pluripotent stem cells. These findings indicate that silencing miR-134 and possibly other microRNAs could be useful to treat clinically relevant phenotypes with a later developmental window in AS., Competing Interests: The Royal College of Surgeons in Ireland (D.C.H.) holds a patent for the inhibition of microRNA-134 for the treatment of seizure-related disorders and other neurologic injuries (US 9,803,200 B2). J.W., M.A.J., and M.T.M. are employees of F Hoffman-La Roche Ltd. All other authors have no competing interests., (© 2022 The Author(s).)

Purpose: Soft tissue reconstructions of the hand require a thin and resistant flap palmarly as well as sliding abilities between the extensor tendons and the flap on the dorsum of the hand. Elasticity is required to maintain the normal wrist range of motion. One option in these cases is the free serratus fascia flap that sometimes shows limitations regarding resistance as well as reliability. Here, we describe an easy modification including a thin muscle cuff in the serratus fascia flap - the serratus carpaccio flap - that improves the ease of flap harvest and morbidity rates., Methods: The indications for the serratus carpaccio flap, the technique of flap harvest and contouring as well as flap inset are described in detail. Clinical examples are given., Results: The main advantage of the serratus carpaccio flap is the ability of the surgeon to adapt the flap thickness to the recipient site requirements. This allows excellent results regarding contour and function. Split thickness skin grafting fromthe instep region of the foot additionally allows optimal results for palmar as well as plantar defect reconstruction. Eighteen flaps for soft tissue defects of the hand (n = 5), foot (n = 10), and lower leg (n = 3) were performed. Complications included one flap loss, one venous re-anastomosis, two partial wound dehiscences and one postoperative hematoma at the donor site. Seventeen flaps survived completely. Secondary thinning procedures were not required., Conclusions: The serratus carpaccio flap is an excellent option for the reconstruction of medium-sized skin and soft tissue defects of the dorsum of the hand or foot, the palm, and the distal forearm., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Soft tissue defects of the foot are very common sequelae after trauma and require an individual reconstructive approach., Objective: Recommendations for the treatment of soft tissue injuries to the foot are given., Material and Methods: The criteria of soft tissue reconstruction, postoperative follow-up and complications are first discussed before the therapeutic approach is explained depending on the reconstruction site. Case examples are given for illustration., Results: Decision making for soft tissue reconstruction of the foot is based on the location, the 3‑dimensional extent of the defect, the patient requirements and concomitant diseases. Standardized treatment algorithms are usually applied that need to be adapted according to individual patient factors. Randomized and local pedicled flaps can be applied for foot reconstruction; however, these options involve a significant risk of complications. Consequently, free flaps are frequently indicated after appropriate preoperative diagnostics of the perfusion of the foot. Due to the vast variety of donor sites, free flaps allow an individualized reconstruction, which is adapted to local and patient requirements., Conclusion: Precise preoperative reconstructive planning and analysis of the vascularization form the foundation for a successful soft tissue reconstruction of the foot. The aims of the individualized approach to soft tissue reconstruction of the foot are stable soft tissue coverage, resistance to weight bearing of the sole of the foot, the ability to wear normal shoes and maintenance of sensibility., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Chronic prevertebral soft tissue defects with exposed metal hardware following spinal surgery represent a challenging complication. Frequently patients underwent multiple previous operations due to wound complications. Surrounding soft tissues are often compromised due to malperfusion, severe subcutaneous scarring, previous local advancement flaps and therefore impair stable wound closure., Methods: Patients after spinal surgery who received complex soft tissue reconstructions between 2011 and 2015 were analyzed retrospectively. Patient`s age, risk factors, wound size, cause and defect location as well as complication rates were evaluated. A focus was set on therapeutic strategies and decision-making concerning reconstructive techniques., Results: Fourteen patients receiving 27 pedicled and one free flap were included in the study. Patients mean age was 51.1 years, mean wound size was 144 cm 2 . Defects were located in the lumbar spine [8], cervical spine [2] and thoracic spine [1], respectively. Three patients suffered from extensive defects affecting more than one area. Mean time of flap surgery was 213 minutes. Fifteen perforator-based flaps and 11 non-perforator (classic rotation-flaps), 1 pedicled and 1 free latissimus dorsi flap were used. In 9 patients (64.3%) different flaps had to be combined in a single-staged procedure due to large wounds. Implant material was removed completely in six patients (42.9%), whereas in five patients (35.7%) implants were replaced within the operation for soft tissue reconstruction. In three patients (21.4%) initial implant removal or replacement was not possible which leads to prolonged postoperative wound infections., Conclusions: Most patients with exposed spinal hardware suffered from multiple comorbidities and showed a poor general condition. Due to the reduced soft tissue quality wound healing is significantly impaired. Exposed implant material should be replaced or removed when possible. Therefore, the complete armamentarium of plastic reconstructive techniques is required for wound closure. Today, perforator flaps play a prominent role due to the variability, excellent vascularization and sufficient subcutaneous filling capacities., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jss-20-688). The authors have no conflicts of interest to declare., (2021 Journal of Spine Surgery. All rights reserved.)

Angelman syndrome (AS) is a severe neurodevelopmental disorder for which only symptomatic treatment with limited benefits is available. AS is caused by mutations affecting the maternally inherited ubiquitin protein ligase E3A (UBE3A) gene. Previous studies showed that the silenced paternal Ube3a gene can be activated by targeting the antisense Ube3a-ATS transcript. We investigated antisense oligonucleotide-induced (ASO-induced) Ube3a-ATS degradation and its ability to induce UBE3A reinstatement and rescue of AS phenotypes in an established Ube3a mouse model. We found that a single intracerebroventricular injection of ASOs at postnatal day 1 (P1) or P21 in AS mice resulted in potent and specific UBE3A reinstatement in the brain, with levels up to 74% of WT levels in the cortex and a full rescue of sensitivity to audiogenic seizures. AS mice treated with ASO at P1 also showed rescue of established AS phenotypes, such as open field and forced swim test behaviors, and significant improvement on the reversed rotarod. Hippocampal plasticity of treated AS mice was comparable to WT but not significantly different from PBS-treated AS mice. No rescue was observed for the marble burying and nest building phenotypes. Our findings highlight the promise of ASO-mediated reactivation of UBE3A as a disease-modifying treatment for AS.

Background: Cerebrospinal fluid (CSF) levels of monoamine metabolites may represent biomarkers of Parkinson's disease (PD)., Objective: The aim of this study was quantification of multiple metabolites in CSF from PD versus healthy control subjects (HCs), including longitudinal analysis., Methods: Absolute levels of multiple monoamine metabolites in CSF were quantified by liquid chromatography coupled with tandem mass spectrometry from 161 individuals with early PD and 115 HCs from the Parkinson's Progression Marker Initiative and de novo PD (DeNoPA) studies., Results: Baseline levels of homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were lower in individuals with PD compared with HCs. HVA levels correlated with Movement Disorder Society Unified Parkinson's Disease Rating Scale total scores (P < 0.01). Both HVA/dopamine and DOPAC/dopamine levels correlated with caudate nucleus and raw DOPAC with putamen dopamine transporter single-photon emission computed tomography uptake ratios (P < 0.01). No metabolite changed over 2 years in drug-naive individuals, but some changed on starting levodopa treatment., Conclusions: HVA and DOPAC CSF levels mirrored nigrostriatal pathway damage, confirming the central role of dopaminergic degeneration in early PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Interleukin 6 (IL-6) is an established biomarker of inflammation with one of the earliest responses in sepsis. Serum levels can easily be measured within a few hours. The clinical significance of IL-6 in the early stage of sepsis in burned patients has not yet been confirmed. The purpose of our research was to investigate the predictive value of IL-6 for positive blood cultures in comparison to Procalcitonin (PCT), white blood cell (WBC) count, body temperature and the Sequential Organ Failure Assessment (SOFA) score in the presence of suspected sepsis in burn patients. In a retrospective study, we included all patients admitted to a regional burn centre in a 7-year period. Patients with a clinical suspicion of sepsis and complete laboratory tests underwent further analysis. Patients were categorized following culture results into either positive or negative bloodstream infection (BSI or non-BSI) groups. 39 of the 101 included patients had positive blood cultures (BSI). The serum IL-6 levels were significantly higher in the BSI group [1047 (339.9; 9000.5) vs. 198.5 (112.4; 702.5) ng/l; P = 0.001]. Receiver operating characteristic (ROC) curve analysis showed an AUC of 0.7 (59; 80.8%). The optimal IL-6 cut-off level was 312.8 ng/l (sensitivity 79.5%, specificity 56.5%). Other biomarkers (PCT, WBC), the maximum body temperature and increase of SOFA score were not different between the groups. IL-6 can be used to predict a positive blood culture even in the early stage of suspected sepsis in burned patients. In this context, other biomarkers (PCT, WBC) and body temperature are of limited clinical utility., Competing Interests: None., (IJBT Copyright © 2021.)

Introduction:  Since its introduction in 2013 Bromelain-based Enzymatic Debridement (ED) is increasingly used in burn centers. Published evidence shows its efficiency in eschar removal as well as a superiority in blood loss and necessity of further surgical procedures compared to standard-of-care. While the procedure is safe and shows reliable results in experienced hands, some practical and logistical issues must be challenged that are not described sufficiently in available literature., Method:  A multi-professional panel, consisting of experienced users of ED from German-speaking burn units has been invited to an expert workshop. Topics concerning indication, definition of treatment pathways, practical issues, post-treatment and handling of complications have been coordinated in advance to allow discussion during the workshop., Results:  To each topic practical recommendations were developed and consented. Summarizing key messages have been additionally highlighted. They aim on helping to achieve optimal results after establishing the technique by new users as well as optimizing results by experienced users. Amongst others, the resulting recommendations deal with indications for ED beyond the classic domain, different treatment pathways depending on burn depth and primary result after ED with adapted post-treatment, management of treatment failure and implementation of infrastructural conditions., Discussion:  While efficiency of ED as well as superiority in some aspects of treatment of burn wounds could be shown in available literature, user-oriented recommendations for practical implementation are scarce. Although the recommendations and experts opinions published here are only partly evidenced based, they are still based on the pooled experienced of the panelists that easily outnumbers the cases published in literature so far and allow valuable support for a successful implementation of the technique., Competing Interests: Benjamin Ziegler hat Vorträge für MediWound Germany GmbH gehalten.Cord Corterier hat keine Interessenkonflikte anzugeben.Thomas Kremer hat keine Interessenkonflikte anzugeben.David Lumenta hat keine Interessenkonflikte anzugeben.Jan Plock ist Berater für MediWound Germany GmbH.Sandy Richter hat keine Interessenkonflikte anzugeben.Frank Sander ist Berater für MediWound Germany GmbH.Jennifer Schiefer ist Beraterin für MediWound Germany GmbHLaura Siegwart hat keine Interessenkonflikte anzugeben.Martin Stauder ist Berater für MediWound Germany GmbH.Christoph Wallner hat keine Interessenskonflikte anzugeben.Dirk Wiechmann hat keine Interessenkonflikte anzugeben.Christoph Hirche hat als Berater für MediWound Germany GmbH gearbeitet.Der Konsensusworkshop wurde durch die BG Klinik Ludwigshafen organisiert und ausgerichtet. Durch unabhängige, wissenschaftliche Drittmittel von MediWound Germany GmbH wurde der Workshop organisatorisch unterstützt., (Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany.)

Background: In cases of anterior interosseous nerve (AIN) syndrome, it is often difficult to differentiate between compression neuropathy and neuritis., Material and Methods: This review analyses the clinical aspects of the neuritic AIN syndrome and the different diagnostic tools for securing the diagnosis and differentiating the condition from compression neuropathy. Based on these data, the current therapeutic options are proposed., Results: The AIN syndrome often results from neuritis of the AIN fascicles within the trunk of the median nerve. The differentiation between neuritis and compression neuropathy of the AIN is based on dedicated neurophysiological examinations as well as nerve sonography and MRI neurography. Although conservative treatment is the gold standard, microsurgical interventions have become more important in recent years., Conclusion: A dedicated diagnostic workup of the AIN syndrome is paramount for optimal treatment. Conservative treatment remains the standard to date. However, if torsions and constrictions of nerve fascicles are detected, intrafascicular neurolysis should be considered, as current research shows the potential for an improved outcome in such cases., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction: Full-thickness soft tissue defects of the back remain challenging clinical problems for reconstructive surgeons. Among a vast variety of local flap options, perforator-based local flaps gain increasing popularity lately. Because mostly heterogeneous patient cohort comparison of different perforator flaps is difficult and decision-making algorithms are lacking., Methods: Patients, who received a local perforator-based soft tissue reconstruction between 2012 and 2019, were evaluated retrospectively. Patients' data were evaluated in terms of flap type and dimension, wound size and cause, surgery time, postoperative complications, and hospitalization. A focus was set on decision making concerning reconstructive techniques and flap choice for defect closure., Results: Thirty-six patients (17 women, 19 men) were included, who received 40 perforator-based local flaps to reconstruct extended defects of the posterior trunk. Mean patient age was 56.3 years and mean hospitalization was 29 days. Average time of flap surgery was 179.7 minutes. Mean flap size was 160.8 cm and average defect size was 110 cm. Defects occurred because of tumor resection (50%), orthopedic/trauma surgery (16.7%), or pressure sores (33.3%). Twenty-eight propeller flaps (PPFs, 70%) and 12 perforator-based VY-advancement flaps (P-VYF, 30%) were transferred. In 4 patients, a bilateral approach using more than one flap was necessary. Revision surgery was required in 9 patients (25%) because of postoperative hematoma (n = 3), postoperative wound infection (n = 3), partial flap necrosis (1× P-VYF) and 2 flap losses (2× PPFs)., Conclusions: Pedicled perforator flaps are a reliable option for soft tissue reconstruction of complex wounds of the posterior trunk. A flexible surgical strategy is mandatory, and the individual perforator anatomy has to be considered. In most cases, P-VYFs or PPFs are reliably possible and allow sufficient defect reconstruction. However, skin incisions should always be performed in a way that classic random pattern flaps are still possible. Even in large defects combined, local perforator flaps may lead to sustainable soft tissue reconstructions without functional donor site deficits.

In sepsis and burns, ascorbic acid (AA) is hypothesized advantageous during volume resuscitation. There is uncertainty regarding its safety and dosing. This study evaluated high dose AA (HDAA: 66 mg/kg/h for 24 hours) versus low dose AA (LDAA: 3.5 g/days) administration during the first 24 hours in severely burned adults. We conducted a retrospective study comparing fluid administration before and after switching from low dose to HDAA in severely burned adults. A total of 38 adults with burns >20% TBSA, who received either HDAA or LDAA were included in this retrospective study. AA serum concentrations were quantified at 0, 24, and 72 hours postburn. HDAA impact on hemodynamics, acid-base homeostasis, acute kidney injury, vasopressor use, resuscitation fluid requirement, urinary output, and the incidence of adverse effects was evaluated; secondary clinical outcomes were analyzed. AA plasma levels were 10-fold elevated in the LDAA and 150-fold elevated in the HDAA group at 24 hours and decreased in both groups afterwards. HDAA was not associated with a significantly increased risk of any complications. A significant reduction in colloid fluid requirements was noted (LDAA: 947 ± 1722 ml/24 hours vs HDAA: 278 ± 667 ml/24 hours, P = 0.029). Other hemodynamic and resuscitation measures, as well as secondary clinical outcomes were comparable between groups. HDAA was associated with higher AA levels and lower volumes of colloids in adults with severe burns. The rate of adverse events was not significantly higher in patients treated with HDAA. Future studies should consider prolonged administration of AA., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Schizophrenia is a severe mental disorder in which epigenetic mechanisms may contribute to illness risk. Epigenetic profiles can be derived from blood cells, but to our knowledge, it is unknown whether these predict established brain alterations associated with schizophrenia., Objective: To identify an epigenetic signature (quantified as polymethylation score [PMS]) of schizophrenia using machine learning applied to genome-wide blood DNA-methylation data; evaluate whether differences in blood-derived PMS are mirrored in data from postmortem brain samples; test whether the PMS is associated with alterations of dorsolateral prefrontal cortex hippocampal (DLPFC-HC) connectivity during working memory in healthy controls (HC); explore the association between interactions between polygenic and epigenetic risk with DLPFC-HC connectivity; and test the specificity of the signature compared with other serious psychiatric disorders., Design, Setting, and Participants: In this case-control study conducted from 2008 to 2018 in sites in Germany, the United Kingdom, the United States, and Australia, blood DNA-methylation data from 2230 whole-blood samples from 6 independent cohorts comprising HC (1238 [55.5%]) and participants with schizophrenia (803 [36.0%]), bipolar disorder (39 [1.7%]), major depressive disorder 35 [1.6%]), and autism (27 [1.2%]), and first-degree relatives of all patient groups (88 [3.9%]) were analyzed. DNA-methylation data were further explored from 244 postmortem DLPFC samples from 136 HC and 108 patients with schizophrenia. Neuroimaging and genome-wide association data were available for 393 HC. The latter data was used to calculate a polygenic risk score (PRS) for schizophrenia. The data were analyzed in 2019., Main Outcomes and Measures: The accuracy of schizophrenia control classification based on machine learning using epigenetic data; association of schizophrenia PMS scores with DLPFC-HC connectivity; and association of the interaction between PRS and PMS with DLPFC-HC connectivity., Results: This study included 7488 participants (4395 men [58.7%]), of whom 3158 (2230 men [70.6%]) received a diagnosis of schizophrenia. The PMS signature was associated with schizophrenia across 3 independent data sets (area under the curve [AUC] from 0.69 to 0.78; P value from 0.049 to 1.24 × 10-7) and data from postmortem DLPFC samples (AUC = 0.63; P = 1.42 × 10-4), but not with major depressive disorder (AUC = 0.51; P = .16), autism (AUC = 0.53; P = .66), or bipolar disorder (AUC = 0.58; P = .21). Pathways contributing most to the classification included synaptic processes. Healthy controls with schizophrenia-like PMS showed significantly altered DLPFC-HC connectivity (validation methylation/magnetic resonance imaging, t < -3.81; P for familywise error, <.04; validation magnetic resonance imaging, t < -3.54; P for familywise error, <.02), mirroring the lack of functional decoupling in schizophrenia. There was no significant association of the interaction between PMS and PRS with DLPFC-HC connectivity (P > .19)., Conclusions and Relevance: We identified a reproducible blood DNA-methylation signature specific for schizophrenia that was correlated with altered functional DLPFC-HC coupling during working memory and mapped to methylation differences found in DLPFC postmortem samples. This indicates a possible epigenetic contribution to a schizophrenia intermediate phenotype and suggests that PMS could be of interest to be studied in the context of multimodal biomarkers for disease stratification and treatment personalization.

We recruited 25 patients after complete wrist denervation and 60 healthy adults to investigate conscious and unconscious proprioception of the wrist. Ipsi- and contralateral joint-position sense, force sense, and wrist reflexes were measured. The latter were triggered by a trapdoor, recording electromyographic signals from the extensor carpi radialis brevis, extensor carpi ulnaris, flexor carpi radialis, and flexor carpi ulnaris muscles. No significant differences were found for joint position sense, force sense, and wrist reflexes between both groups, except for reflex time of the flexor carpi ulnaris after denervation of the left wrist as compared with the left flexor carpi ulnaris in controls or in right operated wrists. At a mean follow-up of 32 months (range 8 to 133), we found no proprioceptive deficit of the conscious proprioceptive qualities of joint position sense, force sense, and the unconscious proprioceptive neuromuscular control of wrist reflex time for most muscles after complete wrist denervation. We conclude from this study that complete wrist denervation does not affect the proprioceptive senses of joint position, force sense, and reflex time of the wrist.

Microsurgical training courses are an integral part of surgical education and training. Due to the changes in the surgical everyday routine, the competence and skills training outside the operating room has an increasingly important status. Multi-day, hands-on exercises with different models of increasing difficulty use artificial, avital and vital microsurgical models. The skills are evaluated with regard to fine motor skills as well as orientation in space and low-tremor motion sequences as well as bimanual manipulation exercises by means of "lobal rating scales". However, with numerous course offerings in German-speaking countries, there are no uniform and transparent contents and evaluation standards to reflect the quality of the courses. At a consensus meeting, minimum requirements for the contents of microsurgical training courses in the context of continuing medical education were defined and drafted as a German-language consensus in order to award a DAM quality seal. The parameters include the definition of targets, the existence of a scripts, the number of hours used, models used, practical exercise time on the microscope, trainer to participant ratio, types of anastomosis or coaptation (artery, vein, nerve, lymph vessel), application of a global rating scale , examination (grade/passed - failed), participant certificate and course evaluation. With the aim to meet the available courses/course concepts to maintain or improve the quality of education and training, the assignment of a "Basic" and an "Advanced" quality seal has been defined. The further stepwise development of the courses is necessary to sustain all skills and competencies for future microsurgeons. Integration of validated microsurgical simulators may reduce animal use and thus contribute to the ethical responsibility. The introduction of quality seals for microsurgical training courses should strengthen the transparency and commitment of participants and provide support to course providers with appropriately substantiated content through DAM., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Talar osteochondral lesions (OCLs) lead to progressive stages of talar destruction. Core decompression with cancellous bone grafting (CBG) is a common treatment for Berndt and Harty stages II and III. However, in a subset of patients, talar revascularization may fail. Surgical angiogenesis using vascularized medial femoral condyle (MFC) autografts may improve on these outcomes. These 2 treatment strategies were directly compared via a prospective preliminary randomized trial including 20 participants with talar core decompression followed by either cancellous (CBG group, n = 10) or vascularized MFC (MFC group, n = 10) bone grafting. Outcome analysis was performed with visual analog scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Lower Extremity Functional Scale (LEFS), and contrast-enhanced magnetic resonance imaging (MRI) scans. At 12 months of follow-up, the mean VAS score was reduced from 6.6 ± 2.5 preoperatively to 4 ± 1.9 in the CBG group and from 5.2 ± 2.9 preoperatively to 1 ± 1.1 in the MFC group (p < .001). The LEFS improved from 53.4 ± 13.1 to 62.6 ± 16.2 CBG and from 53 ± 9.3 to 72.4 ± 7.4 MFC (p = .114). AOFAS improved from 71 ± 12.1 to 84.1 ± 12.5 in CBG and from 70.5 ± 7.4 to 95.1 ± 4.8 in MFC (p = .019). The MRI scans in the CBG group demonstrated 9 partial malperfusions and 1 hypervascularized bone graft, whereas the MFC group had 8 well-vascularized grafts incorporated into the talus and 1 partial malperfusion. Vascularized MFC autografts provide superior pain relief along with improvement of physical function in patients with talar OCL stage II and III compared with CBG. To confirm these promising results, further multicenter randomized controlled trials are required., (Copyright © 2019 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Vascularized bone grafts from the medial femoral condyle (MFC) are used to gain surgical revascularization of osseous defects. To date objective data regarding the donor site morbidity are limited. This study aims to evaluate the donor site associated outcome after MFC flap harvest., Patients and Methods: From 2008 to 2016, 22 patients who underwent MFC bone flap harvest for osseous revascularization of 9 talus, 8 scaphoids, 2 metacarpals, 1 phalanx, 1 pilon tibiale, and 1 distal femur were included. Outcome analysis was performed for the whole cohort as well as for two subgroups (recipient site upper [group A] and lower extremity [group B]) by the lower extremity functional scale (LEFS), the OAK-score of the Swiss Orthopedic Society and the visual analog scale (VAS). Additionally, a 3D gait analysis was performed for four patients., Results: The mean flap size was 1 × 1 × 3 cm. No flap loss was observed. One minor surgical revision was performed due to donor site hematoma. Mean follow-up was 35.8 (12-98) months. Mean LEFS-score was 74.9 ± 9.5 (A: 74.3 ± 7.9; B: 75.6 ± 11.2, p > .05) and OAK-score was 92.8 ± 9.4 (A: 93.2 ± 5.8; B: 92.4 ± 12.3, p > .05). At follow-up examination, pain at rest was stated with 0.1 ± 0.2 (A: 0.1 ± 0.3; B 0 ± 0, p > .05) and with activity 0.6 ± 1.4 (A: 1.2 ± 1.8; B: 0 ± 0, p > .05) on VAS. The 3-D gait analysis showed normative walking patterns., Conclusion: After MFC flap harvest knee function and gait pattern were almost unimpaired. Donor site morbidity can be considered as being of minor concern in the decision-making for this microvascular procedure., (© 2019 Wiley Periodicals, Inc.)

Objective: Severe burn injuries are associated with a rapid escalating hypermetabolic state and catabolism of muscle mass. To ameliorate this process a standardized approach using pharmacological and non-pharmacological interventions was implemented within a single burns center. Whilst individual components of this standardized package are well documented in the literature, their collective or bundled effect has not as yet been assessed. The aim of this study was to evaluate the efficacy of this standardized bundle of metabolic modulators and assess the safety of including the anabolic steroid oxandrolone within it. Methods: This retrospective observational study constituted all patients in whom the metabolic bundle including oxandrolone therapy was applied. The other elements of the metabolic bundle consisted of early surgical burn excision within seven days to completion, early active mobilization, increased ambient room temperature, expediated carbohydrate and protein rich enteral feeding with glutamine and trace element supplements (such as copper and zinc). Finally, administration of propranolol as a non-selective beta-blocker. Data collection was through review of the patient data management system focusing on the outcome criteria and hepatic blood values. Results: The study looked at fifty consecutive patients meeting the inclusion criteria. Median patient age and burned total body surface area (TBSA) were 62 years [51.75; 73] and 33.75% [24.75; 51] respectively with an abbreviated burn severity index (ABSI) of 10 [9; 10.25]. Definitive surgical burn wound excision was completed in 44 patients [88%] within 7 days. 39 patients (78%) received propranolol over a therapeutic period of 29 days [19; 44]. Glutamine was supplemented in 45 patients (90%), while zinc and copper were applied to 42 (84%) and 31 (62%) respectively. Significant low zinc values were noted at therapeutic onset (6.5 mmol/l [4.7; 7.9]) requiring sustained substitution over 37.5 days [22; 46.75]). In respect of the inclusion criteria, all patients received oxandrolone at 20 mg/day [20; 20]. This was commenced on day 6.5 [4; 14] post burn injury and continued over 26 days [19; 31]. Despite a transitory elevation of hepatic enzyme values (ALT, GGT), these were only clinically relevant (>10 µmol/l*S) in 2.4% and 4.6% of all measurements respectively. None were sufficiently of concern to merit cessation of treatment. Conclusion: The application of a standardised bundle of metabolic treatment options of severe burns injured patients is reliable, repeatable and safe. Potential concerns of oxandrolone treatment regarding hepatic compromise remain unfounded., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2019 Taha et al.)

Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht.

Introduction: A recent survey among plastic surgery residents and directors of microsurgical clinics demonstrates a great interest in high- quality microsurgery education. Unfortunately, due to economic pressures, limited operating resources as well as forensic considerations, it has become a challenge to provide sufficient on-the-job training, which needs to be shifted outside of the OR. To promote microsurgical teaching, the German-speaking Working Group for Microsurgery of Peripheral Nerves and Vessels (DAM) organises two-day microsurgery academies to provide interested colleagues with a broad spectrum of microsurgical procedures. In this publication, we present the workshop concept and an evaluation of the first three years., Material and Methods: Since 2015, a two-day workshop has been held at the BG Trauma Centre in Ludwigshafen on a yearly basis. Each day, at least three surgical procedures were performed simultaneously in the area of breast, nerve, bone/hand, extremity and lymph reconstruction, along with presentations regarding the various cases, diseases and specific operative challenges. To evaluate this course concept, we asked participants to identify their expectations and evaluate the academy and its program., Results: The academy and its goals were demonstrated. In a second step, the evaluation, conducted by 79 % of participants, was presented. 67 % of participants were consultants or residents in their final year. 90 % worked at maximum care facilities or university hospitals. 57 % reported that less than 5 microsurgery cases are performed at their institution per week. All participants considered microsurgery to be part of their future work spectrum, with the greatest fields of interest being extremity reconstruction (90 %) or microsurgical reconstruction of the hand (80 %). All participants would recommend the course to their colleagues, but suggest improving the intraoperative video monitoring., Discussion: This work demonstrates that hands-on academies for microsurgery are a highly relevant teaching format, which can counteract the limitations of surgical residency training. In particular, the close contact between senior and junior surgeons was considered highly relevant for building a network within German microsurgery. The overall goal of the academy is to improve teaching and increase the enthusiasm of future microsurgeons and provide a network for German microsurgeons during their training and beyond., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Burn-injured patients are at particularly high risk of infection; as such one would expect an increased requirement of antibiotics compared to other intensive care patients. There is no data in the literature investigating this hypothesis in Germany. The aim of this study was to determine the antibiotic consumption in severe burn patients and to compare this data with those from surgical intensive care units., Patients and Methods: The retrospective study included 136 patients treated in the period from 2013 to 2016 due to a severe burn in the ICU intensive care unit of a regional burn centre. The use of antibiotics was recorded using the electronic medical record. The number of daily doses in Recommended Daily Dose (RDD) and Defined Daily Dose (DDD) based on patient days was calculated., Results: Median [interquartile range] age and total burned surface area were 56.5y [43-75y] and 17 % [8,75; 31] with an ABSI 7 [6; 9]. Antibiotic therapy was given to 82 patients (60.3 %). Antibiotic consumption totaled 77.38 RDD/100 PT or 937.64 DDD/1000 PT. This result was marginally lower than for surgical intensive care units. The most frequently used antibiotics in the burn care setting were fluorquinolones (16.90 RDD/100 PT, 259.91 DDD/1000 PT), followed by carbapenems (12.76 RDD/100 PT, 128.44 DDD/1000 PT) and aminopenicillins/ BLI (11.54 RDD/100 PT, 115.39 DDD/1000 PT). Whilst, the most frequently detected pathogens were Staphylococcus aureus (54.4 %), Enterococcus faecalis (54.4 %), E. coli (37.5 %) and Pseudomonas aeruginosa (36.8 %)., Conclusion: The total antibiotic consumption in severe burns was not increased compared to other surgical intensive care patients. With regard to individual substance classes, peculiarities can be identified reflecting the particular germ spectrum in this cohort., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Mutations in the GBA gene, encoding the lysosomal hydrolase glucocerebrosidase (GCase), are the most common known genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The present study aims to gain more insight into changes in lysosomal activity in different brain regions of sporadic PD and DLB patients, screened for GBA variants. Enzymatic activities of GCase, β-hexosaminidase, and cathepsin D were measured in the frontal cortex, putamen, and substantia nigra (SN) of a cohort of patients with advanced PD and DLB as well as age-matched non-demented controls (n = 15/group) using fluorometric assays. Decreased activity of GCase (- 21%) and of cathepsin D (- 15%) was found in the SN and frontal cortex of patients with PD and DLB compared to controls, respectively. Population stratification was applied based on GBA genotype, showing substantially lower GCase activity (~ - 40%) in GBA variant carriers in all regions. GCase activity was further significantly decreased in the SN of PD and DLB patients without GBA variants in comparison to controls without GBA variants. Our results show decreased GCase activity in brains of PD and DLB patients with and without GBA variants, most pronounced in the SN. The results of our study confirm findings from previous studies, suggesting a role for GCase in GBA-associated as well as sporadic PD and DLB.

The most common donor-site for autologous breast reconstruction is the abdomen. Over the past several decades technical advances have resulted in the development of flaps that have been associated with a progressive decrease in abdominal wall morbidity. However, controversy exists related to the differences between muscle-sparing (MS)-TRAM and deep inferior epigastric perforator (DIEP) flaps. Hence, the question which approach should be considered standard of care remains unanswered. To address this question the current literature and published evidence was critically reviewed and discussed by an expert panel at the 39th Annual Meeting of the German-speaking Society for Micro surgery of the Peripheral Nerves and Vessels (DAM). Based on this discussion a consensus statement was developed that incorporates contemporary data regarding postoperative complication rate, donor site morbidity, as well as expert opinion regarding technical details in autologous breast reconstruction with free TRAM and DIEP flaps., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Competing Interests: Interessenkonflikt: Die Autoren geben an, dass kein Interessenkonflikt besteht.