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Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) frequently causes both healthcare-associated infections and nosocomial outbreaks in burn medicine/plastic surgery and beyond. Owing to the high antibiotic resistance, infections are difficult to treat, and patient outcomes are often compromised. The environmental persistence capability of CRAB favors its transmission in hospitals. A comprehensive analysis and understanding of CRAB epidemiology and microbiology are essential for guiding management., Methods: A three-year retrospective cohort study (2020-2022) was conducted in a German tertiary burn and plastic surgery center. In addition to epidemiological analyses, microbiological and molecular techniques, including whole-genome sequencing, were applied for the comprehensive examination of isolates from CRAB-positive patients., Results: During the study period, eight CRAB cases were found, corresponding to an overall incidence of 0.2 CRAB cases per 100 cases and an incidence density of 0.35 CRAB cases per 1000 patient-days. Six cases (75%) were treated in the burn intensive care unit, and four cases (50%) acquired CRAB in the hospital. Molecular analyses comprising 74 isolates supported the epidemiologic assumption that hospital acquisitions occurred within two separate clusters. In one of these clusters, environmental CRAB contamination of anesthesia equipment may have enabled transmission. Furthermore, molecular diversity of CRAB isolates within patients was observed., Conclusions: CRAB can pose a challenge in terms of infection prevention and control, especially if cases are clustered in time and space on a ward. Our study demonstrates that high-resolution phylogenetic analysis of several bacterial isolates from single patients can greatly aid in understanding transmission chains and helps to take precision control measures., (© 2024. The Author(s).)

Secondary reconstruction in trauma surgery is crucial for restoring both functional and esthetic results in patients with complex defects. Established reconstructive techniques in plastic surgery offer a wide range of options for an effective treatment. This applies not only to covering large defects with free flaps but especially also for the functional reconstruction of bony, neural and musculotendinous impairments. Advances in the fields of microsurgery and 3D printing show innovative approaches to further improve the therapeutic options. A multidisciplinary approach, requiring close collaboration between trauma and plastic surgeons, is necessary to optimize treatment plans and outcomes. The effective management of complications and qualified postoperative care are essential for the success of reconstructive measures., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: The availability of appropriate conduits remains an obstacle for successful reconstruction of long-distance nerve defects. In previous sheep trials, we were able to bridge 6 cm nerve gaps with nerve conduits based on spider silk fibers with full functional outcomes. Here, we describe the first application of spider silk for nerve repair in humans., Methods: Four patients with extended nerve defects (>20 cm) underwent nerve reconstruction by interposition of conduits that were composed of spider silk fibers contained in autologous veins. The longitudinal luminal fibers (approx. 2500 fibers per graft) consisted of drag line silk from Trichonephila spiders. All patients were evaluated between 2 and 10 years postreconstruction, clinically, and by neurography., Results: In all patients, primary wound healing and no adverse reactions to the implanted spider silk material were observed. Patients regained the following relevant functions: protective sensibility, full flexor function with near-normal grasp and powerful function after microvascular gracilis muscle transfer, and key grip function and gross finger flexion after additional tenodesis. One patient with sciatic nerve reconstruction developed protective sensibility of the lower leg, foot, and gait, enabling normal walking and jogging. No neuroma formation or neuropathic or chronic pain occurred in any of the patients., Conclusions: For patients with extended peripheral nerve defects in the extremities, use of conduits based on spider silk fibers offers the possibility of restoring sensory function and protection from neuroma. This kind of nerve bridges provides new perspectives for the reconstruction of complex and long-distance nerve defects., Competing Interests: Competing interests: The authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Breast cancer is the most commonly diagnosed malignant neoplasia in females worldwide. Overall survival and patients' choice for bilateral mastectomy have increased. It is therefore important to offer breast reconstructive procedures to improve patient quality of life and self-esteem. The aim of this systematic literature review is to quantify the outcome and sustainability of bilateral breast reconstruction using autologous, vascularized free tissue transfer., Methods: A systematic literature review of PubMed, Cochrane, and the Web of Science databases was performed. A total of 5879 citations were identified, and 12 studies met the inclusion criteria., Results: A total of 1316 patients were included, with a mean age of 47.2 years. Overall, 32.5% of patients experienced a complication after breast reconstruction. If reported, 7.45% of patients experienced major complications, while 20.7% had minor complications.The following flaps were used for breast reconstruction, in order of reducing frequency: DIEP (45.45%), TRAM (22.73%), SIEA (9.09%), SGAP (9.09%), TUG (4.55%), TMG (4.55%), and LD/MLD (4.55%)., Conclusions: Current studies indicate that bilateral breast reconstruction using autologous, vascularized free tissue transfer is a safe procedure for postmastectomy reconstruction and offers stable long-term results. This is particularly in comparison to implant-based breast reconstruction., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Preserved allogeneic donor skin still represents one of the gold standard therapies in temporary wound coverage in severely burned patients or chronic wounds. Allogeneic skin grafts are currently commercially available as cryo- or glycerol-preserved allografts through skin tissue banks all over the world. Most of the skin tissue banks rely on human cadaveric skin donations. Due to the chronic shortage of human allogeneic transplants, such as skin, and increasing costs in the procurement of allografts from other skin tissue banks, Hannover Medical School has been building up its own skin tissue bank based on allogeneic skin grafts from living donors who underwent surgical treatment (i.e., body-contouring procedures, such as abdominioplasties). This article presents procedures and protocols for the procurement and processing of allogeneic skin grafts according to national legislation and European regulations and guidelines. Beside protocols, initial microbiological data regarding the sterility of the harvested grafts are presented. The results currently form the basis for further investigations as well as clinical applications. In summary, a microbiological testing and acceptance procedure is presented that ensures adequate patient safety and skin viability., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

We carried out a retrospective single-center study and analyzed all patients who have been admitted to our intensive care burn unit following suicide attempt and accidental burns within 14 years. Clinical and demographic parameters were collected and evaluated. Propensity score matching was performed in order to minimize the confounding effect of the parameters age, sex, total body surface area (TBSA), and the presence of full-thickness burns and inhalation injury. 45 burn patients following attempted suicide by burning and 1266 patients following accidental burn injury were admitted. Patients with suicidal burn injuries were significantly younger and showed significantly higher burn severity, reflected by larger TBSA affected, higher incidence of full-thickness burns and inhalation injury. They also experienced increased hospital length of stay (LOS) and longer ventilation durations. Their in-hospital mortality was significantly higher. Following propensity score matching in 42 case pairs, no differences were detected with regard to in-hospital mortality, hospital LOS, duration of mechanical ventilation, and frequency of surgical interventions. Attempted suicide by burning is associated with overall worse outcomes and higher mortality rates. Following propensity score matching, significant differences in outcomes were no longer detectable. Given the comparable survival probability compared to accidentally burned patients, life-sustaining treatment should not be withheld in burn patients following suicide attempt., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Functional facial reanimation remains challenging and the quest for optimization continues. Objective: To characterize the anatomical conditions of the plantaris muscle for facial reanimation. Study Design and Methods: Forty-two plantaris muscle specimens were obtained from 23 post-mortem chemically fixed cadavers. The muscles were dissected, evaluated, and measured. Mock facial reanimation was performed on three cadaver heads. Results: The plantaris muscle was a consistently available muscle. Mean muscle belly length was 10.1 cm (standard deviation [SD] 1.4), and mean width was 1.7 cm (SD 0.4). The mean tendon length of 30.1 cm (SD 2.8) is unique in the human body. The main artery supplying the muscle had a mean length of 1.4 cm (SD 0.4). The mean nerve length was 2.2 cm (SD 0.7). Sixteen variations of vascular supply were identified. Mock facial reanimations demonstrated a good size match, and great versatility of the long tendon for oral fixation. Conclusions: The plantaris muscle as a free flap for facial reanimation could offer new possibilities in terms of oral fixation and volumetric aesthetic conditions.

Aims: Globally, burn-related morbidity and mortality still remain high. In order to identify regional high-risk populations and to suggest appropriate prevention measure allocation, we aimed at analyzing epidemiological characteristics, etiology and outcomes of our 14-year experience with an intensive care unit (ICU) burn patient population., Methods: A retrospective observational study was conducted including patients treated between March 2007 and December 2020 in our intensive care burn unit. Demographic, clinical and epidemiological data were collected and analyzed., Results: A total of 1359 patients were included. 68% of the subjects were males and the largest age group affected entailed 45-64-year-old adults (34%). Regarding etiology, flame and contact burns were the most common in all age groups. Mean affected total body surface area (TBSA) was 13 ± 14.5% in all subjects. Most of the burns occurred domestically or during recreational activities. Mean hospital stay was 17.77 ± 19.7 days. The average mortality was 7.7%. The mortality rate showed an overall decreasing trend whilst burn severity remained consistent from 2007 to 2020., Conclusions: Despite consistent burn severity presentations of annual ICU admissions, burn injury mortality showed a decreasing trend, which was in part attributed to substantial progress in burn care and treatment and improved burn prevention awareness. Statistically significant age and gender differences could be detected with regard to burn etiology and seasonality, as well as outcomes, which highlight the importance of individualized primary prevention programs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd and ISBI. All rights reserved.)

Aims: Patients with psychiatric comorbidity have been shown to experience high rates of burn injury. Burn epidemiology, etiology, and outcomes have been sparsely documented for patients with major psychiatric disorders. The aim of this study was to analyze the epidemiologic characteristics and outcomes in intensive care burn patients with pre-existing and acute major psychiatric disorders ., Methods: A retrospective study was performed including intensive care burn patients admitted between March 2007 and December 2020. Demographic, clinical and epidemiological data were collected and analyzed. Major psychiatric co-morbidities were collected according to ICD-9 and ICD-10 classifications. Patients were stratified according to F-diagnoses., Results: A total of 1325 patients were included. 16.6 % of all patients had one or more major psychiatric disorders- 9.3 % with anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders, 9.2 % with mood (affective) disorders, 3.5 % with schizophrenia and other non-mood psychotic disorders, and 1.8 % with disorders of adult personality and behavior. Patients with major psychiatric disorders presented with significantly higher burn severity, reflected by higher abbreviated burn severity index (ABSI) scores (5.9 vs. 5.3, p < 0.001) and larger total body surface area (TBSA) affected (15.9 vs. 12.5 %, p = 0.002). Burned TBSA ≥ 30 and inhalation injuries were observed more frequently in patients with MDP, however without statistical significance. They also experienced prolonged hospital length-of-stay (LOS) (25.5 vs. 16.3 days, p < 0.001), prolonged intensive care unit LOS (14.8 vs. 7.7 days, p < 0.001), underwent surgical interventions (3.5 vs. 2.3, p < 0.001) and mechanical ventilation more frequently (34.1 % vs. 16.5 %, p = 0.43) and had significantly longer ventilation durations (73.5 vs. 31.2 h, p = 0.002). Mortality rates were lower compared to patients without major psychiatric disorders (5.9 vs. 8.1, p < 0.001)., Conclusions: The prevalence of major psychiatric disorders in burn patients is considerably high. Patients with psychiatric comorbidities were found to have greater burn severity, prolonged total hospital and ICU LOS, underwent surgical interventions and mechanical ventilation more frequently and had prolonged ventilation duration. Our results highlight the importance of identifying burn patients with major psychiatric disorders who may necessitate additional resources and require extensive inpatient psychiatric care and counseling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Background: E-cigarette abuse, also known as vaping, is a widespread habit. Recently, there have been increasing reports of explosions of these devices resulting in serious burn injuries, especially to the groin, hand, and face. Overheating rechargeable lithium-ion batteries are supposed to be the responsible mechanism, especially in low quality fabrications., Methods: In this single-center retrospective study, data of 46 patients are presented and analyzed. In addition to information on demographics, injury patterns, and treatment options, this is the first study investigating outcome after an average of 13 months via a standardized telephone interview of 31 patients (67%). Patients were specifically asked regarding their outcome, vaping habits, technical modifications to their devices and supply source., Results: Patients were mainly male (98.2%) with a median age of 36 years. Typical injury patterns included the groin region (n = 32; 69%), hands (n = 12; 25%) and face (n = 3; 7%). All patients underwent debridement, in nine cases hydrotherapeutically. 61% (n = 28) underwent consecutive tangential necrectomy and subsequent split thickness skin graft transplantation. Wound infection was observed in 18 patients (39%), with burn depth as a significant risk factor (p < 0.001). 91% of the followed-up patients were satisfied. Surprisingly, 38% were still using e-cigarettes. 42% (n = 13) reported manual modifications of their devices to prolong battery life or increasing smoke production., Conclusions: Injuries from exploding e-cigarettes can be serious and should be treated in a specialized burn center. E-cigarette explosions lead to characteristic injury patterns and often need surgical treatment. This should be made more public to reduce their use and keep people from modifying the devices. The counterintuitive and irrational observation of a high rate of abuse even after the injury underlines their addiction potential., Competing Interests: The authors have no competing interest to declare., (© 2023 The Author(s).)

Background: Interdisciplinary case conferences are well-established in the field of oncology in order to provide the best possible treatment for patients with complex disease patterns which overlap several disciplines., Methods: After studying the available literature the aims, indications, frequency, patient enrolment and documentation modalities, disciplines necessary to create the reconstruction plan and evaluation parameters of the board, were agreed in an interdisciplinary discussion among colleagues. The utilization of the extremity board and demographic features of the cases presented in the extremity board within the first 6 months were subsequently descriptively analyzed., Results: The agreed primary aim of an extremity board is the timely and transparent preparation of a high-quality holistic reconstruction plan for optimized treatment of a challenging patient collective with complex injuries of the extremities. Decisive interfaces of an extremity board are the participation of interdisciplinary disciplines, established enrolment and documentation modalities and a longitudinal analysis of parameters of the acute medical treatment, the long-term function and quality of life of those affected. The patient collective so far mostly includes men under 40 years old with traumatic soft tissue defects and combined injuries. On average, reconstruction plans for 1-2 patients were approved in an interdisciplinary team per session., Conclusion: The extremity board serves as a platform for coordinated planning of treatment for patients with complex injuries. The limited personnel and time resources represent the greatest challenge for the successful implementation. The extremity board enables a high degree of interdisciplinary networking. The digital registration and documentation modality within the internal hospital documentation system is of utmost relevance. The preparation of the reconstruction plan is of decisive importance for the qualitative success of treatment and the restoration of function. The longitudinal analysis of appropriate parameters is imperative to measure the quality of treatment., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Complex and chronic wounds represent a highly prevalent condition worldwide that requires a multimodal and interdisciplinary treatment approach to achieve good functional and aesthetic outcomes. Due to increasing costs of health care, an aging population and an increase in difficult-to-treat microbial colonization of wounds, complex wounds will become a substantial clinical, social and economic challenge in the upcoming years. In plastic reconstructive surgery, a variety of dermal skin substitutes have been established for clinical use. Since its approval as a dermal skin substitute in Germany, NovoSorb ® Biodegradable Temporising Matrix (BTM) has become a valuable therapeutic option for the treatment of full-thickness wound defects. The clinical data published to date are limited to case reports and small-scale case series with the main focus on single wounds. The aim of this single-center study was a retrospective analysis of our own patient collective that has received treatment with BTM for complex wounds. Overall, BTM showed to be a reliable and versatile reconstructive option, especially for patients with multiple co-morbidities and microbiologically colonized wounds. Although the preliminary findings have produced promising results, further investigation and research are warranted regarding long-term outcomes and additional clinical applications.

Peyronellaea pinodes is a devastating pathogen of pea crop. Quantitative trait loci (QTL) associated with resistance have been identified, as well as genes differentially expressed between resistant and susceptible pea lines. The key question is which of these many genes located into these QTLs, or differentially expressed, are the key genes that distinguish resistant from susceptible plants and could be used as markers. To identify these key genes, in the present study we applied MACE (Massive Analysis of cDNA Ends) -Seq to a whole Recombinant Inbred Line population segregating for resistance to this disease and their parental lines and identified those genes which expression was more correlated with the level of resistance. We also compared gene expression profiles between the most resistant and the most susceptible families of the RIL population. A total of 6780 transcripts were differentially expressed between the parental lines after inoculation. Of them, 803 showed the same expression pattern in the bulks formed by the most resistant and most susceptible RIL families. These genes, showing a consistent expression pattern, could be used as expression markers to distinguish resistant from susceptible plants. The analysis of these genes also discovered the crucial mechanisms acting against P. pinodes., (© 2022. The Author(s).)

Background: The global COVID-19 pandemic has led to social constraints and changes in injury patterns during the government-imposed restrictions. The aim of this study was to evaluate the effects of the lockdown period on the pattern of emergency presentations in a plastic, hand and reconstructive surgery department in a German referral center., Methods: A retrospective cohort study was conducted comparing patients presenting during the enforced lockdown period in 2020 and the same pre-pandemic period during the previous year 2019. All emergency presentations in the emergency unit requiring treatment by plastic, hand and reconstructive surgery were included. Patient demographics, reason for presentation, need for hospital admission, body region affected, location of injury and/or occurrence of first clinical symptoms and injuries of anatomical structures were considered., Results: Demographics were comparable among both groups. A 42.7% reduction in emergency cases was observed during the lockdown period. A significant elevation of domestic injuries and symptoms in the pandemic group (51.54% vs. 66.15%, p  = 0.007) was registered. Concurrently, a decrease in recreational injuries (27.31% vs. 15.38%, p  = 0.009) and workplace injuries (10.57% vs. 7.69%, p  = 0.37) was noted. Hospital admission rates and length of stay were comparable. Similarly, no statistically significant differences could be detected regarding injuries of functional anatomical structures. The same holds true for crush injuries, animal bites, fall injuries, finger amputations, disc saw injuries, and distortion injuries. Fractures of the phalanges, the metacarpus/carpus and the forearm exhibited an increase., Conclusions: In spite of decreasing total emergency caseloads, there was an unchanged need for plastic, hand and reconstructive in-patient surgery and care during the lockdown period. Resource allocation has to be considered in future pandemic waves. Prevention strategies are warranted and should focus on finding measures to counteract domestic injuries., Competing Interests: None., (© 2022 The Authors.)

Liquid body contouring by intramuscular injection of site-enhancing oils (SEOs) for muscle volume enlargement has increasingly become a popular practice in bodybuilding. Its immediate and long-term health consequences remain ambiguous, and postinjection complications are sparsely documented in medical literature. We report a series of patients presenting with postinjection complications upon self-attempted liquid body contouring through injection of SEOs. Ten patients visited our departments for plastic and reconstructive surgery for variable local and systemic complications. All patients gave a history of single or multiple SEO use and presented on average nine years postinjection with variable complications. Most patients experienced painful nodular indurations and swellings in the injected target muscles. Two patients showed signs of infection including erythema, fever, and local inflammatory findings. One patient presented additionally with a severe form of nonparathyroid hypercalcemia. Four patients ultimately underwent surgical treatment. The use of SEOs for liquid body contouring is a dangerous practice and is associated with potentially systemic and life-threatening complications. Surgical treatment may be the only therapeutic option in advanced cases and should be performed timely. Guidelines on diagnostic and therapeutic measures are warranted. Educational measures should be undertaken to raise awareness among athletes and medical professionals., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The interest in youthful appearance and rejuvenating procedures is unbroken in our society. Besides surgical procedures, permanent fillers are utilized. The incorrect and unprofessional use of these substances, auto-injections in particular, have devastating results for patients and are challenging for the plastic surgeon. The aim of this retrospective study was to delineate the differences between permanent and non-permanent filler complications and appropriate treatment options., Methods: We conducted a retrospective study and researched the hospital information system in the time period from 2001 to 2020. Patients with unprofessional use of permanent fillers, auto-injections and injections of unformulated substances were determined. Age, gender, localization, complications, length of hospital stay, comorbidities, histopathological workups and surgical salvage procedures were noted. Descriptive statistics were calculated., Results: Seventeen patients were identified from 2001 till 2020. In four cases, auto-injections by the patients were the cause, whereas in the other patients the injections were performed by medical staff. Ages range from 18 to 57 years. Fourteen patients were female and three were male. The injected substances could be recognized as synthol, silicone, vaseline, fat tissue, hyaluronic acid as well as non-medical substances. Surgical procedures were necessary in eleven cases. One patient died because of the underlying diseases., Conclusion: Our results indicate different sequels of filler materials injected in an unprofessional way, possible complications, conservative and surgical techniques to resolve these rare complications. We suggest a staged therapy adjusted to the clinical symptoms. Milder symptoms can be handled conservatively, whereas severe infections, skin breakdowns or persistent granuloma are justifying indications for surgical treatment., Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2021. The Author(s).)

Genetic engineering is a promising tool to repair genetic disorders, improve graft function, or reduce immune responses toward allografts. Ex vivo organ perfusion systems have the potential to mitigate ischemic-reperfusion injury, prolong preservation time, or even rescue organ function. We aim at combining both technologies to develop a modular platform allowing the genetic modification of vascularized composite (VC) allografts. Rat hind limbs were perfused ex vivo under subnormothermic conditions with lentiviral vectors. Specific perfusion conditions such as controlled pressure, temperature, and flow rates were optimized to support the genetic modification of the limbs. Genetic modification was detected in vascular, muscular, and dermal limb tissues. Remarkably, skin follicular and interfollicular keratinocytes, as well as endothelial cells showed stable transgene expression. Furthermore, levels of injury markers such as lactate, myoglobin, and lactate dehydrogenase, as well as histological analyses showed that ex vivo limb perfusion with lentiviral vectors did not cause tissue damage and limb cytokine secretion signatures were not significantly affected. The use of ex vivo VC perfusion in combination with lentiviral vectors allows an efficient and stable genetic modification representing a robust platform to genetically engineer limbs toward increasing graft survival after transplantation.

The treatment of traumatic major upper limb amputation is complex and of great urgency. Loss of time often represents a majorrestriction for replantation. Thus, logistical and infrastructural developments, such as the expansion of specialised hand trauma centres, are crucial for optimizing delivery of care. Surveillance represents the fundament for a proper, demand-adapted implementation of such therapeutical improvements. However, a comprehensive database for surveillance of these injuries does currently not exist in Germany or Europe. In this study quality reports of German hospitals from 2014 to 2018 were screened retrospectively for traumatic major upper extremity amputations and replantations. A total of 329 amputations and 87 replantations were recorded, accounting for an overall replantation rate (RR) of 26%. Most of the injuries affected the level of the wrist and forearm. Treatment of these injuries experienced an increasing centralisation to medical teaching facilities, which accounted for higher RRs compared with non-teaching facilities. The cumulatively most populous federal states handled most of the amputation injures in this five-year study period. Ratio calculations on the basis of population counts, however, revealed great discrepancies to these results, with Hamburg, Rhineland-Palatinate and Saarland accounting for the highest per capita incidences. In 2018 Germany was provided with 46 specialised hand trauma and replantation centres, which performed 45% of the replantations in that year, revealing a RR of 17%, compared to an overall RR of 14% in that year. Nevertheless, there might be potential for improvement in the geographical distribution of these specialised centres. The provision of highly specialised therapy in highly specialised centres for highly complex injuries is a future challenge in replantation surgery. This data is contributing to logistical improvements for a need-adapted expansion of these specialised hand trauma centres. The study demonstrates an approach of a standardised and comprehensive injury surveillance program based on national quality reports, while underlining the importance of such a national or rather European database for optimisations in medical care. Level of evidence IV., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Prof. Dr. Kai Megerle is a member of the FESSH Research Committee as well as coordinator of the German FESSH Hand Trauma Centres., (© 2022 The Authors. Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.)

Purpose: Therapeutic success of surgical interventions is significantly affected by patients' adherence. Patient autonomy can lead to unreasonable behavior. We analyzed the consequences and predisposing factors of patient self-discharge in a plastic and hand surgery cohort., Study Design and Setting: Data was collected retrospectively in a case-control study with n = 73 patients who had self-discharged in a 10-year time period and n = 130 controls (discharge by the surgeon). Data was collected through the hospital information systems and a particular questionnaire. Statistical analyses were performed via chi-squared test and logistic regression analyses., Results: Patients who self-discharged against medical advice had a significantly higher complication rate (p = 0.045) and a higher number of revision operations (p < 0.001). They were more often dissatisfied with the primary inpatient treatment (p < 0.05). Secondly, they lived more often in shared households (p = 0.002; OR 5.387 (1.734-16.732)) or had to take care of their children at home (p = 0.006; OR 1.481 (1.280-1.741)). There was a significantly lower pain score (NAS) on time of self-discharge (p = 0.002) as well as 24 h after self-discharge (p < 0.001) in self-discharged patients., Conclusion: Self-discharge was associated with predisposing factors and poorer outcomes. Patient autonomy can lead to health-compromising behavior and patients should be counseled accordingly., (© 2021. The Author(s).)

Conduct Disorder (CD) is an impairing psychiatric disorder of childhood and adolescence characterized by aggressive and dissocial behavior. Environmental factors such as maternal smoking during pregnancy, socio-economic status, trauma, or early life stress are associated with CD. Although the number of females with CD is rising in Western societies, CD is under-researched in female cohorts. We aimed at exploring the epigenetic signature of females with CD and its relation to psychosocial and environmental risk factors. We performed HpaII sensitive genome-wide methylation sequencing of 49 CD girls and 50 matched typically developing controls and linear regression models to identify differentially methylated CpG loci (tags) and regions. Significant tags and regions were mapped to the respective genes and tested for enrichment in pathways and brain developmental processes. Finally, epigenetic signatures were tested as mediators for CD-associated risk factors. We identified a 12% increased methylation 5' of the neurite modulator SLITRK5 (FDR = 0.0046) in cases within a glucocorticoid receptor binding site. Functionally, methylation positively correlated with gene expression in lymphoblastoid cell lines. At systems-level, genes (uncorr. P < 0.01) were associated with development of neurons, neurite outgrowth or neuronal developmental processes. At gene expression level, the associated gene-networks are activated perinatally and during early childhood in neocortical regions, thalamus and striatum, and expressed in amygdala and hippocampus. Specifically, the epigenetic signatures of the gene network activated in the thalamus during early childhood correlated with the effect of parental education on CD status possibly mediating its protective effect. The differential methylation patterns identified in females with CD are likely to affect genes that are expressed in brain regions previously indicated in CD. We provide suggestive evidence that protective effects are likely mediated by epigenetic mechanisms impairing specific brain developmental networks and therefore exerting a long-term effect on neural functions in CD. Our results are exploratory and thus, further replication is needed., Competing Interests: All the authors of this manuscript declare to have no conflict of interest interfering with any part of the work presented in the manuscript. BR and NK are affiliated with the commercial research company genXpro GmbH, which analyzed the methylation data. Samples were blinded and phenotypic data were not available to the company. Neither BR nor NK did have any additional role in the study design or statistical analysis. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Infections of the hand and forearm are a frequently seen surgical emergency of the hand. Patients of all age groups are affected and underlying systemic diseases are risk factors. Posttraumatic causes are the leading cause of infections. This includes cuts and stab wounds, animal and human bites but often also minor injuries. Due to the anatomical peculiarities of the hand, rapid progression of initially inconspicuous infections can occur resulting in functional limitations. If an infection is suspected, a symptom-oriented evaluation by a hand surgeon should be performed. This includes a detailed patient history, clinical examination, laboratory analyses and imaging. This is followed by the development of an individualized and interdisciplinary treatment concept with the aim of achieving the shortest possible rehabilitation period. The treatment includes surgical cleansing of the infection, accompanied by antibiotic treatment taking the expected possible spectrum of pathogens into account. Cephalosporins and aminopenicillins in combination with beta-lactamase inhibitors are the antibiotics of first choice. Follow-up treatment includes early functional exercise under the guidance of a hand therapist to minimize postinfectious restrictions in the range of motion and to enable occupational rehabilitation. In rare cases, fulminant necrotizing infections with resulting skin and soft tissue defects can occur. In these cases, secondary plastic reconstruction is usually required after cleansing of the infection., (© 2021. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Early detection of sepsis is of crucial importance in patients with severe burn injuries. However, according to the S1-guideline, based on systemic inflammatory response syndrome (SIRS) criteria, the early diagnosis of sepsis in severely burned patients is difficult. The value of the new definition of sepsis based on sequential organ failure assessment (SOFA) according to S3-guidelines for patients with severe burn injuries is not described in detail in the literature. We analyzed retrospectively all data during the period 2014 to 2018 from the electronic patient information system. Using the receiver operating characteristic curve, the area under the curve was calculated for the diagnostic value of procalcitonin, SIRS, and SOFA score according to the burned total body surface area. Six hundred fifty-one patients with burn injuries were admitted to our burn unit, 315 of them had burn injuries affecting more than 10% body surface area with partial- to full-thickness burns (grade 2-4). In this group, 59 patients showed one or more septic events in the course of the intensive care treatment, defined by positive bloodstream infection. Both S1- and S3-guidelines were inappropriate to diagnose sepsis in patients with severe burn injuries. Due to pathophysiological changes of the body function in severely burned patients, which show features of both SIRS and pathological SOFA scores (>2 points) at the outset of burn injury, the diagnosis of sepsis associated with burns is intricate in this patient group. Assessing data for potential hallmarks of sepsis in burn patients we found procalcitonin to show a significant correlation with sepsis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Ligament suspension after trapeziectomy is a common technique in patients with osteoarthrosis. In this study, we set out to determine whether the orientation of the bone tunnel in the first metacarpal base affects the intraoperative position of the first metacarpal after surgery. Methods: Trapeziectomy and Epping procedure were performed in 32 cadaver hands. A drill hole was placed in the base of the first metacarpal, leaving a radial to ulnar tunnel parallel to the joint surface or a diagonal bone tunnel from the radiodorsal surface to the ulnar joint surface of the first metacarpal. Positioning of the first metacarpal was studied via radiography. Results: The distance between the first metacarpal and the scaphoid after suspension arthroplasty was 9.5 ± 2.6 mm when using the parallel radioulnar bone tunnel and 10.9 ± 2.3 mm when using the diagonal bone tunnel. Suspension of the first metacarpal was 33% higher with the diagonal bone tunnel compared with when using the parallel bone tunnel (displacement of 2.8 ± 2.0 mm vs 4.2 ± 2.0 mm). Conclusions: Higher suspension of the first metacarpal after trapeziectomy can be significantly achieved in our cadaveric model when using ligament suspension of the flexor carpi radialis tendon passed from the ulnar joint surface to the dorsum of the metacarpal. Our results have to be determined via clinical examination. To date, we prefer the diagonal bone tunnel when performing ligament suspension arthroplasty.

Background: Polytraumatized burn patients represent a rare patient collective and necessitate an individualized treatment concept due to the particular combination of injuries., Objective: Against the background of this special injury pattern, especially with deep burns overlying the fracture zone, the question of a specific and interdisciplinary treatment algorithm arises., Material and Methods: This article is based on a PubMed database search and experiences of a trauma center for severely injured burn patients at a university hospital, with presentation of the special therapeutic requirements and goals exemplified by a case report., Results: The evaluation of the literature search and own treatment results comes to the conclusion that the rate and extent of amputations and infections can be reduced by an early and interdisciplinary involvement of the plastic surgeon by early combined fracture stabilization, excision of necrotic tissue and immediate skin grafting. Furthermore, plastic reconstructive procedures enable a functional and esthetic reconstruction with optimized prosthesis fitting., Conclusion: Polytraumatized severely burned patients necessitate an interdisciplinary treatment approach, whereby preservation of length, functionality and esthetic appearance of the affected extremities and concurrent avoidance of bone and soft tissue infections have utmost priority., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Aims: This study aims at assessing the treatment effect, disease severity and quality-of-life outcomes of botulinum toxin (BTX) injections for focal hyperhidrosis., Methods: We included randomized controlled trials of BTX injections compared with placebo for patients with primary or secondary focal hyperhidrosis. PubMed, Embase and the Cochrane Library were searched to August 2020. Gravimetric sweat rate reduction, disease severity measured by Hyperhidrosis Disease Severity Scale and quality-of-life assessment measured by Dermatology Life Quality Index were the outcomes of interest. Cochrane risk-of-bias tools were employed for quality assessment of given randomized controlled trials., Results: Eight studies met our inclusion criteria (n=937). Overall, risk bias was mixed and mostly moderate. BTX injections showed reduced risk in comparison with placebo for the gravimetric quantitative sweat reduction of > 50 % from baseline (risk difference: 0.63, 95% CI 0.51 to 0.74). Additionally, improvements were seen for disease severity and quality-of-life assessments evaluated by Hyperhidrosis Disease Severity Score reduction of ≥ 2 points (risk difference: 0.56, 95% CI 0.42 to 0.69) and mean change in Dermatology Life Quality Index (mean difference: - 5.55, 95% CI - 7.11 to - 3.98). The acquired data were insufficient to assess for long-term outcomes and limited to an eight-week follow-up period., Conclusions: In focal axillary hyperhidrosis, BTX significantly reduces sweat production and yields superior outcomes in assessments of disease severity and quality-of-life. However, the quality-of-evidence is overall moderate and included studies account for short-term trial periods only. Further studies assessing BTX in comparison with first-line treatments for hyperhidrosis are warranted., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2021. The Author(s).)

Laparoscopic liver resection (LLR) is an increasingly relevant treatment option for patients with resectable hepatocellular carcinoma (HCC). Orthotopic liver transplantation (OLT) has been considered optimal treatment for HCC in cirrhosis, but is challenged by rising organ scarcity. While health-related quality of life (HRQoL) and mental health are well-documented after OLT, little is known about HRQoL in HCC patients after LLR. We identified all HCC patients who underwent LLR at our hospital between 2014 and 2018. HRQoL and mental health were assessed using the Short Form 36 and the Hospital Anxiety and Depression Scale, respectively. Outcomes were compared to a historic cohort of HCC patients after OLT. Ninety-eight patients received LLR for HCC. Postoperative morbidity was 25% with 17% minor complications. LLR patients showed similar overall HRQoL and mental health to OLT recipients, except for lower General Health ( p = 0.029) and higher anxiety scores ( p = 0.010). We conclude that LLR can be safely performed in patients with HCC, with or without liver cirrhosis. The postoperative HRQoL and mental health are comparable to that of OLT recipients in most aspects. LLR should thus always be considered an alternative to OLT, especially in times of organ shortage.

Scalds in the elderly are frequently associated with the use of a bathtub and a disturbed consciousness. Therefore, the total burn surface area is often high. The initial clinical presentation displays a stark erythema of the skin, which frequently does not represent the true depth. The aim of this study was to characterize and assess medical features and outcome of scalds sustained in the bathtub. We conducted a retrospective study at a burn intensive care unit (BICU) between 2011 and 2018. Medical features as well as the treatment in these patients were statistically analyzed. We identified 16 patients and divided them into two groups regarding survival and lethality. The mean total burn surface area was 37.50 ± 19.47%. In 81.25% of the patients, we found a previous history of neurological or psychiatric disorders. Dementia and alcohol abuse were the most common triggers for the trauma. The statistical analysis showed a significant difference for the ABSI-score and the presence of multi organ failure (P-value .0462, respectively, .0004). Erythematous skin areas tended to progress into full thickness burns. We, therefore, coined the term "lobster redness" for these regions. Scalds sustained in the bathtub are devastating injuries. Initial assessment can be misleading and might delay early necrectomy. The wounds request even more attention, if the injuries occurred due to unconsciousness because of the longer exposure to heat. Early necrectomy should be considered. A biopsy with histological workup can be useful. Furthermore, we recommend special safety precautions for neurologically and psychiatrically affected patients., (© 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.)

Pyoderma gangrenosum is a diagnosis of exclusion. It occurs rarely and is frequently misdiagnosed. It can result in severe tissue loss, particularly in surgical units with little experience. Nevertheless, surgical treatment might be necessary for reconstruction, once the progression of these wounds is controlled. We aimed to characterize medical findings in Pyoderma patients with extensive defects to assess the surgical procedures and their outcome. A retrospective study was conducted at our centre over an 18-year period. Inclusion criteria were the diagnosis of Pyoderma gangrenosum and at least one surgical intervention. Descriptive statistics were used to analyse the data. Sixteen patients were included. The mean size of the lesions was noted with 12 × 8 cm. Surgical procedures comprised debridements/necrectomies, allograft conditioning, negative pressure wound therapy, skin grafts, and microvascular free flaps. Seven patients were discharged with healed wounds, six with minor wound healing disturbances. Three patients succumbed to their underlying diseases. Drug-based therapy can stop the progress of Pyoderma, but severe tissue loss can be a persistent problem. According to our data, reconstructive-surgical treatments (debridement, autologous and allogenous skin transplantation and microvascular free flaps) act as an integral component of the therapy and can be safe options for selected patients. Furthermore, we provide an algorithm that we follow at our department in severe cases., (© 2021 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

Due to groundbreaking and pioneering developments in the last century, significant improvements in the care of burn patients have been achieved. In addition to the still valid therapeutic standard of autologous split-thickness skin grafting, various commercially available skin substitutes are currently available. Significant progress in the field of tissue engineering has led to the development of promising therapeutic approaches. However, scientific advances in the field of allografting and transplant immunology are of great importance. The achievement of various milestones over the past decades has provided thought-provoking impulses in the field of skin allotransplantation. Thus, biologically viable skin allotransplantation is still not a part of the clinical routine. The purpose of this article is to review the achievements in burn surgery with regards to skin allotransplantation in recent years.

Lyme borreliosis is an emerging tick-borne disease caused by spirochetes Borrelia burgdorferi sensu lato. In Europe, Lyme borreliosis is predominantly caused by Borrelia afzelii and transmitted by Ixodes ricinus . Although Borrelia behavior throughout tick development is quite well documented, specific molecular interactions between Borrelia and the tick have not been satisfactorily examined. Here, we present the first transcriptomic study focused on the expression of tick midgut genes regulated by  Borrelia . By using massive analysis of cDNA ends (MACE), we searched for tick transcripts expressed differentially in the midgut of unfed, 24h-fed, and fully fed I. ricinus nymphs infected with B. afzelii . In total, we identified 553 upregulated and 530 downregulated tick genes and demonstrated that B. afzelii interacts intensively with the tick. Technical and biological validations confirmed the accuracy of the transcriptome. The expression of five validated tick genes was silenced by RNA interference. Silencing of the uncharacterized protein (GXP&#95;Contig&#95;30818) delayed the infection progress and decreased infection prevalence in the target mice tissues. Silencing of other genes did not significantly affect tick feeding nor the transmission of B. afzelii , suggesting a possible role of these genes rather in Borrelia acquisition or persistence in ticks. Identification of genes and proteins exploited by Borrelia during transmission and establishment in a tick could help the development of novel preventive strategies for Lyme borreliosis., Competing Interests: NK and PW were employed by GenXPro GmbH. The remaining 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 © 2021 Mahmood, Sima, Urbanova, Trentelman, Krezdorn, Winter, Kopacek, Hovius and Hajdusek.)

Background: Spare-part surgery is widely accepted and offers an option in extremely traumatized patients for reconstructive maneuvers. Standardized techniques are lacking, and the therapy needs to fit the patient's clinic. Materials and Methods: In a woman with necrosis of almost all extremities due to septic infection, we used the lower leg as a free osteocutaneous flap to reconstruct a basic hand function after amputation. The fibula segment was buried alongside the remaining first metacarpal bone. On the hand stump, 2 short metacarpals were lengthened using the remaining 2 metacarpals as osteovascular on-top plasties. The flap was microsurgically anastomosed end-to-side to the ulnar artery. After 3 months, the buried fibula was trimmed to the necessary thumb length and fixed to the local metacarpal I stump. Secondary procedures were performed to deepen the first web space. Results: The patient is now able to manage her daily life. Also, she is able to put on her prosthesis on both legs and walk without aids. Conclusions: To our knowledge, this is the first description of successful microvascular transfer of an osteocutaneous free flap from an amputated lower leg of this size and could present a valuable technique for other cases.

Ixodes ricinus is the vector for Borrelia afzelii, the predominant cause of Lyme borreliosis in Europe, whereas Ixodes scapularis is the vector for Borrelia burgdorferi in the USA. Transcription of several I. scapularis genes changes in the presence of B. burgdorferi and contributes to successful infection. To what extend B. afzelii influences gene expression in I. ricinus salivary glands is largely unknown. Therefore, we measured expression of uninfected vs. infected tick salivary gland genes during tick feeding using Massive Analysis of cDNA Ends (MACE) and RNAseq, quantifying 26.179 unique transcripts. While tick feeding was the main differentiator, B. afzelii infection significantly affected expression of hundreds of transcripts, including 465 transcripts after 24 h of tick feeding. Validation of the top-20 B. afzelii-upregulated transcripts at 24 h of tick feeding in ten biological genetic distinct replicates showed that expression varied extensively. Three transcripts could be validated, a basic tail protein, a lipocalin and an ixodegrin, and might be involved in B. afzelii transmission. However, vaccination with recombinant forms of these proteins only marginally altered B. afzelii infection in I. ricinus-challenged mice for one of the proteins. Collectively, our data show that identification of tick salivary genes upregulated in the presence of pathogens could serve to identify potential pathogen-blocking vaccine candidates.

Non-classical human monocytes are characterized by high-level expression of cytokines like TNF, but the mechanisms involved are elusive. We have identified miRNAs and CpG-methylation sites that are unique to non-classical monocytes, defined via CD14 and CD16 expression levels. For down-regulated miRNAs that are linked to up-regulated mRNAs the dominant gene ontology term was intracellular signal transduction. This included down-regulated miRNA-20a-5p and miRNA-106b-5p, which both are linked to increased mRNA for the TRIM8 signaling molecule. Methylation analysis revealed 16 hypo-methylated CpG sites upstream of 14 differentially increased mRNAs including 2 sites upstream of TRIM8. Consistent with a positive role in signal transduction, high TRIM8 levels went along with high basal TNF mRNA levels in non-classical monocytes. Since cytokine expression levels in monocytes strongly increase after stimulation with toll-like-receptor ligands, we have analyzed non-classical monocytes (defined via slan expression) after stimulation with lipopolysaccharide (LPS). LPS-stimulated cells continued to have low miRNA-20a and miRNA-106b and high TRIM8 mRNA levels and they showed a 10-fold increase in TNF mRNA. These data suggest that decreased miRNAs and CpG hypo-methylation is linked to enhanced expression of TRIM8 and that this can contribute to the increased TNF levels in non-classical human monocytes., Competing Interests: Declaration of Competing Interest A.M.Z. is currently full-time employee of Fresenius Medical Care; the present work was performed and completed under the previous given affiliation (Saarland University Medical Center). All authors declare no conflict of interest., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: Limb loss has a drastic impact on a patient's life. Severe trauma to the extremities is common in current military conflicts. Among other aspects, "life before limb" damage control surgery hinders immediate replantation within the short post-traumatic timeframe, which is limited in part by the ischemic time for successful replantation. Ex vivo limb perfusion is currently being researched in animal models and shows promising results for its application in human limb replantation and allotransplantation., Presentation of the Hypothesis: The current lack of replantation possibilities in military operations with high rates of amputation can be addressed with the development of a portable ex vivo limb perfusion device, as there are several opportunities present with the introduction of this technique on the horizon. We hypothesize that ex vivo limb perfusion will enable overcoming the critical ischemic time, provide surgical opportunities such as preparation of the stump and limb, allow for spare-part surgery, enable rigorous antibiotic treatment of the limb, reduce ischemia-reperfusion injuries, enable a tissue function assessment before replantation, and enable the development of large limb transplant programs., Testing the Hypothesis: Data from in vivo studies in porcine models are limited by the relatively short perfusion time of 24 h. In the military setting, notably longer perfusion times need to be realized. Therefore, future animal studies must focus especially on long-term perfusion, since this represents the military setting, considering the time for stabilization of the patient until evacuation to a tertiary treatment center., Implications of the Hypothesis: The development and clinical introduction of ex vivo limb perfusion in the military setting could lead to a drastic reduction in the number of limb amputations among service members. Ex vivo limb perfusion enables replantation surgery in Role 4 facilities and changes the clinical setting from a highly urgent, life-threatening situation to a highly methodical, well-prepared starting point for optimal treatment of the wounded service member. With its introduction, the principle of "life before limb" will change to "life before limb before elective replantation/allotransplantation after ex vivo limb perfusion".

Thermal injuries occur in every age group and are caused by flames, fluids, steam and direct contact. They are often trivialized but should actually be treated immediately to reduce secondary complications, such as infections and hypertrophic scars. Besides the pain, large wound areas are given priority. Surgical treatment is necessary if at least second degree (IIb) deep dermal burns are present. In this case the reconstructive surgeon has various techniques in the therapeutic armamentarium. Furthermore, in cases of severe burns a perioperative intensive care monitoring and treatment are obligatory as massive systemic inflammatory response syndrome (SIRS), shock, sepsis, organ failure, fluid resuscitation and complications, such as delirium and exacerbation of pain have been proven to negatively influence the outcome.

Introduction  The main postoperative complication of free flaps is perfusion compromise. Urgent intervention is critical to increase the chances of flap survival. Invasive flap perfusion monitoring with direct blood flow feedback through the Cook-Swartz Doppler probe could enable earlier detection of perfusion complications. Materials and Methods  Between 2012 and 2016, 35 patients underwent breast reconstruction or defect coverage after trauma with a deep inferior epigastric perforator, anterolateral thigh, transverse musculocutaneous gracilis, gracilis, or latissimus dorsi flap in our department. All flaps were monitored with a Cook-Swartz probe for 10 days postoperatively. The 20 MHz probe was placed around the arterial-venous anastomosis. A flap monitoring protocol was established for standardized surveillance of postoperative perfusion. In the event of probe signal loss, immediate surgical revision was initiated. Results  Signal loss was detected in 8 of the 35 cases. On return to the operating room, six were found to be true positives (relevant disruption of flap perfusion) and two were false positives (due to Doppler probe displacement). There were also two false negatives, resulting in a slowly progressive partial flap loss. Flap perfusion was restored in three of the six cases (50%) identified by the probe. Following surgical intervention, three of the six cases had persistent problems with perfusion, resulting in two total flap losses and one partial flap necrosis leading to an overall 5.7% total flap loss. Conclusion  Postoperative flap perfusion surveillance is a complex matter. Surgical experience is often helpful but not always reliable. The costs, false-positive, and false-negative rates associated with invasive perfusion monitoring with Cook-Swartz probe make it most appropriate for buried flaps. Level of Evidence  This is an original work., Competing Interests: Conflict of Interest None.

Concerns about food contamination by Listeria monocytogenes are on the rise with increasing consumption of ready-to-eat foods. Biofilm production of L. monocytogenes is presumed to be one of the ways that confer its increased resistance and persistence in the food chain. In this study, a collection of isolates from foods and food processing environments (FPEs) representing persistent, prevalent, and rarely detected genotypes was evaluated for biofilm forming capacities including adhesion and sessile biomass production under diverse environmental conditions. The quantity of sessile biomass varied according to growth conditions, lineage, serotype as well as genotype but association of clonal complex (CC) 26 genotype with biofilm production was evidenced under cold temperature. In general, relative biofilm productivity of each strain varied inconsistently across growth conditions. Under our experimental conditions, there were no clear associations between biofilm formation efficiency and persistent or prevalent genotypes. Distinct extrinsic factors affected specific steps of biofilm formation. Sudden nutrient deprivation enhanced cellular adhesion while a prolonged nutrient deficiency impeded biofilm maturation. Salt addition increased biofilm production, moreover, nutrient limitation supplemented by salt significantly stimulated biofilm formation. Pan-genome-wide association study (Pan-GWAS) assessed genetic composition with regard to biofilm phenotypes for the first time. The number of reported genes differed depending on the growth conditions and the number of common genes was low. However, a broad overview of the ontology contents revealed similar patterns regardless of the conditions. Functional analysis showed that functions related to transformation/competence and surface proteins including Internalins were highly enriched., (Copyright © 2019 Lee, Cole, Badel-Berchoux, Guillier, Felix, Krezdorn, Hébraud, Bernardi, Sultan and Piveteau.)

Background: A critical barrier to successful limb replantation and allotransplantation is the maximum allowable limb ischemia time of 4 to 6 hours. The current gold standard is to preserve amputated limbs on an ice slurry. Experimental machine perfusion has yielded promising results as an alternative. In particular, hypothermic acellular perfusion has enabled preservation of amputated limbs for up to 12 hours thus far., Methods: Amputated forelimbs of Yorkshire pigs were preserved on static cold storage at 4°C for 4 hours (static cold storage group) or perfused at 8°C for 24 hours (perfusion group) with oxygenated modified STEEN Solution perfusate before replantation. Animals were followed up for 7 days after replantation., Results: Eight animals underwent replantation (cold storage group, n = 4; perfusion group, n = 4). Seventy-five and 100 percent of animals in the static cold storage and perfusion groups survived for 7 days, respectively. Glycogen and adenosine triphosphate remained stable throughout perfusion. Heart and respiratory rate after replantation were increased in the static cold storage group. There was increased damage in muscle biopsy specimens obtained from animals in the static cold storage group after 7 days when compared with those from animals in the perfusion group., Conclusions: Hypothermic acellular ex vivo perfusion of limbs for up to 24 hours enables tissue preservation comparable to that obtained with conventional static cold storage for 4 hours and may reduce muscle damage and systemic reactions on limb replantation. Translation to human limbs may help improve limb replantation and allotransplantation outcomes.

Background: The acquisition of a medical professorship represents a significant step in a physician's academic career. The responsibility as well as the honor and the associated obligations are significant; however, the requirements to become a medical professor vary in Germany., Objective: We analyzed the variable requirements for prospective medical professors in Germany, with special focus on the tenure track concept and the U.S. system., Methods: Based on an online research, we queried German medical faculty regulations to obtain a medical professorship within Germany., Results: We analyzed 35 German universities. On average, 11 publications are required after "venia legendi" to meet professorship (apl) prerequisites (median x̅ = 10, max = 24, min = 6, n = 16), whereas 6 publications with first or last authorship are required on average (x̅ = 6, max = 16, min = 4, n = 26). In most German universities, it takes an average of 4 years after gaining habilitation to apply for a professorship (x̅ = 5 years, max = 6 years, min = 2 years). Candidates for university chair positions, however, can shorten this period by an average of 38%., Discussion: In the German academic system, the prerequisites to gain a professorship differ among universities. Due to different scientific cooperation and exchange programs, research and academic activities have reached an intense international exchange level. Yet there is no international or even national standardization, quality assurance, and comparability to gain a medical professorship., (©2019 Alawi S.A., et al., published by De Gruyter, Berlin/Boston.)

The gibberellin (GA)-sensitive dwarfing gene Ddw1 provides an opportunity to genetically reduce plant height in rye. Genetic analysis in a population of recombinant inbred lines confirmed a monogenetic dominant inheritance of Ddw1 . Significant phenotypic differences in PH between homo- and heterozygotic genotypes indicate an incomplete dominance of Ddw1 . De novo transcriptome sequencing of Ddw1 mutant as well as tall genotypes resulted in 113,547 contigs with an average length of 318 bp covering 36.18 Mbp rye DNA. A hierarchical cluster analysis based on individual groups of rye homologs of functionally characterized rice genes controlling morphological or physiological traits including plant height, flowering time, and source activity identified the gene expression profile of stems at the begin of heading to most comprehensively mirror effects of Ddw1 . Genome-wide expression profiling identified 186 transcripts differentially expressed between semi-dwarf and tall genotypes in stems. In total, 29 novel markers have been established and mapped to a 27.2 cM segment in the distal part of the long arm of chromosome 5R. Ddw1 could be mapped within a 0.4 cM interval co-segregating with a marker representing the C20-GA2-oxidase gene ScGA2ox12 , that is up-regulated in stems of Ddw1 genotypes. The increased expression of ScGA2ox12 observed in semi-dwarf rye as well as structural alterations in transcript sequences associated with the ScGA2ox12 gene implicate, that Ddw1 is a dominant gain-of-function mutant. Integration of the target interval in the wheat reference genome sequence indicated perfect micro-colinearity between the Ddw1 locus and a 831 kb segment on chromosome 5A, which resides inside of a 11.21 Mb interval carrying the GA-sensitive dwarfing gene Rht12 in wheat. The potential of Ddw1 as a breeder's option to improve lodging tolerance in rye is discussed.

Face vascularized composite allografts (FVCAs) have helped patients with severe facial disfigurement, with acute rejection now largely controlled through iatrogenic immunosuppression. However, little is known regarding the incidence and mechanism(s) of more long-term pathologic alterations in FVCAs that may affect function and graft durability. Protocol surveillance biopsy specimens for up to an 8-year interval in 7 patients who received FVCAs at our institution revealed histopathologic evidence of chronic rejection. Clinical manifestations included features of premature aging, mottled leukoderma accentuating suture lines, telangiectasia, and dryness of nasal mucosa. Pathologic changes consisted of epidermal thinning accompanied by discrete foci of lymphocyte-mediated cytotoxicity, hyperkeratosis, follicular plugging, vascular ectasia, and sclerosis beneath the epidermal layer associated with collagen type I deposition. Genomic interrogation and immunohistochemistry of sclerotic zones revealed upregulation of the AP-1 pathway components, JunB and c-Fos, previously implicated in overproduction of type I dermal collagen in the setting of systemic sclerosis. We conclude that some patients develop chronic rejection in FVCAs with striking similarities to alterations seen in certain autoimmune cutaneous disorders (lupus erythematosus and scleroderma/chronic sclerodermoid graft-versus-host disease). Identification of relevant pathways and genes, such as JunB and c-Fos, may provide new targets for preventative therapies for chronic immune-mediated changes in vascularized composite allografts., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Ischemia-reperfusion injury remains the major limiting factor for limb replantation and transplantation. Static cold storage (SCS) on ice currently represents the standard mode of preservation but is limited to 6 h of duration. Ex vivo machine perfusion has evolved as a potential alternative to safely extend the duration of ex vivo preservation by providing continuous supply of oxygen and nutrients. This study aims to evaluate underlying molecular mechanisms of both preservation modalities., Methods: We assessed molecular changes in amputated porcine forelimbs stored on ice at 4°C for 2 h (n = 2) and limbs perfused with Perfadex solution at 10°C for 2 h (n = 3) or 12 h (n = 3) before replantation. Muscle biopsies were examined for histological changes and gene expression levels using H&E staining and a hypoxia-related PCR gene array, respectively., Results: Histology revealed only minor differences between the ice (SCS) and perfusion groups after 2 h of preservation, with decreased muscle fiber disruption in the perfusion groups compared with the ice (SCS) group. Perfused limbs demonstrated downregulation of genes coding for glycolytic pathways and glucose transporters after 2 h and 12 h when compared with SCS after 2 h. Similarly, genes that induce angiogenesis and those that are activated on DNA damage were downregulated in both perfusion groups as compared with SCS., Conclusions: Perfusion of porcine limbs resulted in less activation of hypoxia-related gene families when compared with SCS. This may indicate a state more closely resembling physiological conditions during perfusion and potentially limiting ischemic injury. Our study confirms ex vivo perfusion for up to 12 h as a viable alternative for preservation of vascularized composite tissues., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Altered neuronal development is discussed as the underlying pathogenic mechanism of autism spectrum disorders (ASD). Copy number variations of 16p11.2 have recurrently been identified in individuals with ASD. Of the 29 genes within this region, quinolinate phosphoribosyltransferase ( QPRT ) showed the strongest regulation during neuronal differentiation of SH-SY5Y neuroblastoma cells. We hypothesized a causal relation between this tryptophan metabolism-related enzyme and neuronal differentiation. We thus analyzed the effect of QPRT on the differentiation of SH-SY5Y and specifically focused on neuronal morphology, metabolites of the tryptophan pathway, and the neurodevelopmental transcriptome., Methods: The gene dosage-dependent change of QPRT expression following Chr16p11.2 deletion was investigated in a lymphoblastoid cell line (LCL) of a deletion carrier and compared to his non-carrier parents. Expression of QPRT was tested for correlation with neuromorphology in SH-SY5Y cells. QPRT function was inhibited in SH-SY5Y neuroblastoma cells using (i) siRNA knockdown (KD), (ii) chemical mimicking of loss of QPRT, and (iii) complete CRISPR/Cas9-mediated knock out (KO). QPRT - KD cells underwent morphological analysis. Chemically inhibited and QPRT-KO cells were characterized using viability assays. Additionally, QPRT-KO cells underwent metabolite and whole transcriptome analyses. Genes differentially expressed upon KO of QPRT were tested for enrichment in biological processes and co-regulated gene-networks of the human brain., Results: QPRT expression was reduced in the LCL of the deletion carrier and significantly correlated with the neuritic complexity of SH-SY5Y. The reduction of QPRT altered neuronal morphology of differentiated SH-SY5Y cells. Chemical inhibition as well as complete KO of the gene were lethal upon induction of neuronal differentiation, but not proliferation. The QPRT-associated tryptophan pathway was not affected by KO. At the transcriptome level, genes linked to neurodevelopmental processes and synaptic structures were affected. Differentially regulated genes were enriched for ASD candidates, and co-regulated gene networks were implicated in the development of the dorsolateral prefrontal cortex, the hippocampus, and the amygdala., Conclusions: In this study, QPRT was causally related to in vitro neuronal differentiation of SH-SY5Y cells and affected the regulation of genes and gene networks previously implicated in ASD. Thus, our data suggest that QPRT may play an important role in the pathogenesis of ASD in Chr16p11.2 deletion carriers., Competing Interests: All study participants have given written informed consent, and the genetic study has been positively reviewed by the ethic’s committee Frankfurt (No 267/09).All authors agree to publish the presented work.All authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Despite the obvious advantages, face transplantation requires strict patient selection to guarantee optimal outcomes. Therefore, it is not suitable for all patients with severe facial disfigurements. Simultaneously, conventional plastic and reconstructive surgery techniques, as well as medical spa techniques, have evolved, offering minimally invasive treatment of complex deformities., Methods: The entire face of a young woman was severely disfigured because of a mistreated juvenile acne, with severe ectropions, oral incompetence and substantial midfacial tissue defect. We are describing the reconstruction with a combination of conventional reconstructive methods, such as scar release, skin transplantation, local flaps, medical needling and lipofilling., Results: Oral competence, unhindered breathing and adequate lid closure was achieved. Previously unable to participate in social life in any meaningful way, our patient was able to reintegrate fully and take a job., Conclusion: For selected patients, combined, invasive and non-invasive conventional techniques can provide satisfying outcomes in complex facial reconstruction. Modern regenerative approaches such as lipofilling and medical needling should be considered as integral parts of treatment strategies., (© 2018 The Authors.)

The Lathyrus cicera transcriptome was analysed in response to rust ( Uromyces pisi ) infection to develop novel molecular breeding tools with potential for genetic mapping of resistance in this robust orphan legume species. One RNA-seq library each was generated from control and rust-inoculated leaves from two L. cicera genotypes with contrasting quantitative resistance, de novo assembled into contigs and sequence polymorphisms were identified. In toto , 19,224 SNPs differentiate the susceptible from the partially resistant genotype's transcriptome. In addition, we developed and tested 341 expressed E-SSR markers from the contigs, of which 60.7% varied between the two L. cicera genotypes. A first L. cicera linkage map was created using part of the developed markers in a RIL population from the cross of the two genotypes. This map contains 307 markers, covered 724.2 cM and is organised in 7 major and 2 minor linkage groups, with an average mapping interval of 2.4 cM. The genic markers also enabled us to compare their position in L. cicera map with the physical position of the same markers mapped on Medicago truncatula genome, highlighting a high macrosyntenic conservation between both species. This study provides a large new set of genic polymorphic molecular markers with potential for mapping rust resistances. It represents the first step towards genomics-assisted precision breeding in L. cicera ., Competing Interests: The authors declare no conflict of interest.