Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis.

OBJECTIVE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and severe skin and mucosal reactions that are associated with high mortality. Despite the severity, an evidence-based treatment protocol for SJS/TEN is still lacking. METHOD: In this systematic review and meta-analysis, the PubMed database was searched using the following terms: [Stevens-Johnson syndrome] OR [toxic epidermal necrolysis] AND [therapy] OR [treatment] over a 20-year period (1999-2019) in the German and English language. All clinical studies reporting on the treatment of SJS/TEN were included, and epidemiological and diagnostic aspects of treatment were analysed. A meta-analysis was conducted on all comparative clinical studies that met the inclusion criteria. RESULTS: A total of 88 studies met the inclusion criteria, reporting outcomes in 2647 patients. Treatment was either supportive or used systemic corticosteroid, intravenous immunoglobulin, plasmapheresis, cyclosporine, thalidomide or cyclophosphamide therapy. The meta-analysis included 16 (18%) studies, reporting outcomes in 976 (37%) patients. Systemic glucocorticoids showed a survival benefit for SJS/TEN patients in all analyses compared with other forms of treatment. Cyclosporine treatment also showed promising results, despite being used in a small cohort of patients. No beneficial effects on mortality could be demonstrated for intravenous immunoglobulins. CONCLUSION: Glucocorticoids and cyclosporine may be tentatively recommended as the most promising immunomodulatory therapies for SJS/TEN, but these results should be investigated in future prospective controlled trials.

Optimising management of self-inflicted burns: a retrospective review.

OBJECTIVE: Self-inflicted burns typically result in extensive injuries requiring intensive care and attention in a specialised burn unit. Burn units should be familiar with the optimal management of self-inflicted burns, including the psychological and psychiatric treatment. This paper describes the experiences of managing these challenging injuries in a German burn centre. METHODS: A retrospective review of patients with self-inflicted burns admitted to the burn centre between 2000 and 2017. Demographics, details of injury, presence of psychiatric disorder, clinical course, operative management and patient outcomes were recorded and compared with a control group without self-inflicted burns. Outcome measures included graft take rate, complications and need for further surgery. RESULTS: There were a total of 2055 burn patient admissions, with 17 cases (0.8%) of self-inflicted burns. The mean age was 36±11 years with an mean percentage total body surface area (%TBSA) burned of 43.5±22.5% which was not significantly different from the control group (p=0.184). Schizophrenia and personality disorder were the most common diagnoses in the self-inflicted burns patients (n=11; 65%). Of these, four had sustained previous self-inflicted burns. Length of hospital stay was significantly longer in the self-inflicted burn group than in the control group (49.0±16.7 days, respectively, p=0.002). CONCLUSION: Attempted suicide by self-inflicted burns represents <1% of burn admissions. This population demonstrates a high incidence of prior psychiatric disorders. Successful treatment includes multidisciplinary management of acute medical, surgical, and psychiatric care.

[Management of severe sepsis using a Cytokin-adsorber]. / Management einer schweren Sepsis unter Einsatz eines Zytokin-Adsorbers.

Based on a representative case, which was treated in our center for severe burn injuries, the severity of the Waterhouse-Friderichsen syndrome and the complexity of the prolonged course of treatment are illustrated. Special attention is focused on the new treatment paradigm using the CytoSorb® adsorber.

Repetitive transcranial magnetic stimulation (rTMS) in schizophrenia with treatment-refractory auditory hallucinations and major self-mutilation.

Major self-mutilation is one of the most hazardous complications encountered in psychiatric patients, and is generally associated with auditory verbal hallucinations as part of a psychotic syndrome. This case report exemplarily discusses the treatment of such hallucinations with repeated (20 sessions) low-frequency (1 Hz) transcranial magnetic stimulation targeting areas of elevated metabolic activity in the temporo-parietal cortex ('neuronavigated rTMS'), drawing upon experience concerning treatment of a patient with chronic auditory verbal hallucinations that had proved intractable to antipsychotic medication combined with cognitive behavioural therapy, and who had severed a forearm because of the content of these hallucinations. This example of major self-mutilation underscores the urgent requirement for effective management of chronic auditory verbal hallucinations in patients suffering from psychiatric disease, and neuronavigated rTMS represents an approach that deserves further exploration in this regard.

Pressure makes diamonds? The impact of closed incision negative pressure wound therapy on complications following abdominoplasty in patients with massive weight loss-results from a case controlled trial.

Background: The effectiveness of closed incision negative pressure wound therapy (ciNPWT) has been shown across various studies. However, studies with large patient cohorts comprising post-bariatric patient populations are missing. The objective of this research was to assess the influence of ciNPWT on post-operative wound complications in this demanding patient collective. Methods: We conducted a retrospective case-control study. Between 1 January 2013 and 31 December 2023, a total of 251 abdominoplasty procedures following massive weight loss were identified. Patients were matched based on resection weights. We matched 118 patients separated into two groups depending on post-surgical wound management (conventional wound dressings vs ciNPWT). The primary outcomes were wound-related disorders and secondary outcomes were the number of readmissions or reoperations within 30 days after the initial surgery. Results: The study revealed equal incidence of seroma formation (15 vs 15, p = 1.0), rates of wound dehiscence (23 vs 20, p = 0.56), surgical site infection (11 vs 6, p = 0.18), hematoma (17 vs 9, p = 0.07), complete removal of all drainages (6.7 vs 6.1 days, p = 0.34) and total number of readmission (12 vs 11, p = 0.77) or reoperations (12 vs 10, p = 0.63) within 30 days. The second hospital stay caused by revision was significantly shorter in the ciNPWT group (5.8 days vs 12.0 days, p = 0.02). Conclusion: Consequently, we did not find evidence to support the hypothesis that ciNPWT reduces complications after abdominoplasty in patients with massive weight loss.

Hyperspectral Imaging Detects Clitoral Vascular Issues in Gender-Affirming Surgery.

The aim of this study was to assess the efficacy of hyperspectral imaging (HSI) as an intraoperative perfusion imaging modality during gender affirmation surgery (GAS). The hypothesis posited that HSI could quantify perfusion to the clitoral complex, thereby enabling the prediction of either uneventful wound healing or the occurrence of necrosis. In this non-randomised prospective clinical study, we enrolled 30 patients who underwent GAS in the form of vaginoplasty with the preparation of a clitoral complex from 2020 to 2024 and compared patients' characteristics as well as HSI data regarding clitoris necrosis. Individuals demonstrating uneventful wound healing pertaining to the clitoral complex were designated as Group A. Patients with complete necrosis of the neo-clitoris were assigned to Group B. Patient characteristics were collected and subsequently a comparative analysis carried out. No significant difference in patient characteristics was observed between the two groups. Necrosis occurred when both StO2 and NIR PI parameters fell below 40%. For the simultaneous occurrence of StO2 and NIR PI of 40% or less, a sensitivity of 92% and specificity of 72% was calculated. Intraoperatively, the onset of necrosis in the clitoral complex can be reliably predicted with the assistance of HSI.

Translation, Cross-Cultural Adaptation and Validation of the Lymphedema Quality of Life Questionnaire (LYMQOL) in German-Speaking Patients with Lymphedema of the Lower Limbs.

The LYMQOL Leg questionnaire is the most widely used, evidence-based tool for the assessment of health-related quality of life (HRQoL) in patients with lower limb lymphedema (LLL). It has been translated into several languages, but a German version is currently lacking. The aim of our study was to validate a German translation of LYMQOL Leg. Translation and cross-cultural adaptation were performed in accordance with ISPOR principles. A total of 103 patients with LLL from Germany, Austria, and Switzerland were interviewed twice. The content and face validity assessments indicated that the German LYMQOL Leg questionnaire was acceptable for interviewing patients with lymphedema. Comparing the LYMQOL Leg with the SF-36 demonstrated good construct validity. Reliability determined by the test-retest procedure was good (intra-class-correlation coefficients 0.68-0.92). Cronbach's alpha values ranged from 0.76 to 0.90 in both interviews, showing an acceptable internal consistency. The four domains of the questionnaire reached a cumulative variance of 52.7% in the factor analysis. The association between the lymphedema stages and the LYMQOL Leg domain scores was not significant. In conclusion, the validity of the German version of LYMQOL Leg, called LYMQOL Bein, was confirmed and thus represents a suitable tool for measuring HRQoL in German-speaking patients with LLL.

A Platform for Testing the Biocompatibility of Implants: Silicone Induces a Proinflammatory Response in a 3D Skin Equivalent.

Biocompatibility testing of materials is carried out in 2D cell cultures or animal models despite serious limitations. 3D skin equivalents are advanced in vitro models for human skin. Silicone has been shown to be noncytotoxic but capable of eliciting an immune response. Our aim was to (1) establish a 3D skin equivalent to (2) assess the proinflammatory properties of silicone. We developed a coculture of keratinocytes and fibroblasts resulting in a 3D skin equivalent with an implant using samples from a breast implant. Samples with and without the silicone implant were studied histologically and immunohistochemically in comparison to native human skin samples. Cytotoxicity was assessed via LDH-assay, and cytokine response was assessed via ELISA. Histologically, our 3D skin equivalents had a four-layered epidermal and a dermal component. The presence of tight junctions was demonstrated in immunofluorescence. The only difference in 3D skin equivalents with implants was an epidermal thinning. Implanting the silicone samples did not cause more cell death, however, an inflammatory cytokine response was triggered. We were able to establish an organotypical 3D skin equivalent with an implant, which can be utilised for studies on biocompatibility of materials. This first integration of silicone into a 3D skin equivalent confirmed previous findings on silicone being non-cell-toxic but capable of exerting a proinflammatory effect.

Translation, Cross-Cultural Adaptation and Validation of the Lymphedema Quality of Life Questionnaire (LYMQOL) in German-Speaking Patients with Upper Limb Lymphedema.

Objectives: The LYMQOL is the most frequently translated, validated, objective tool for assessing Health-Related Quality of Life (HRQoL) in individuals with upper limb lymphedema (ULL). There have been adaptations and validations in a number of different countries. While a German version of LYMQOL Leg for lower limb lymphedema is available, a validated translation of LYMQOL Arm to German is lacking. We aimed to perform a cross-cultural adaption and translation according to ISPOR principles. Methods: Patients suffering from ULL from Germany, Austria, and Switzerland (n = 52) were questioned twice using the translated LYMQOL Arm, SF-36, and an evaluation questionnaire. The assessment of the content validity and face validity proved this version of LYMQOL Arm to be acceptable for interviewing German-speaking patients with ULL in Germany. Results: Comparison of LYMQOL Arm and SF-36 demonstrated good construct validity. Test-retest reliability was moderate to good (intraclass correlation coefficients 0.66-0.73). Cronbach's alpha values varied between 0.79 and 0.89 in both interviews, indicating good internal consistency. Factor analysis revealed a cumulative variance of 59.5% for the four domains of the questionnaire. Conclusion: There was no significant association between lymphedema stage and LYMQOL Arm score. This trial tested the appropriateness of the German version of the LYMQOL Arm for measuring HRQoL in German-speaking individuals with ULL.

Diagnostical accuracy of hyperspectral imaging after free flap surgery.

Microsurgical free-tissue transfer has been a safe option for tissue reconstruction. This study aimed to analyze the diagnostic accuracy of hyperspectral imaging (HSI) after free-tissue transfer surgery. From January 2017 to October 2019, 42 consecutive free-flap surgeries were performed, and their outcomes were analyzed via HSI. Clinical examination of free-flap perfusion was initially performed. Clinical examination findings were subsequently compared with those of HSI. Potential venous congestion with subsequent necrosis was defined as a tissue hemoglobin index of ≥53%. Student's t-test was used to compare the results of the analysis. The evaluation of sensitivity and specificity for flap failure detection was time dependent using the Fisher's exact test. A p-value of ≤0.05 was considered statistically significant. Microsurgical tissue transfer success rate was 84%. Seven patients presented with venous congestion that caused total flap necrosis. Overall, 124 assessments were made. HSI accurately identified 12 out of 19 pathological images: four as false positive and seven as false negative. The sensitivity and specificity of HSI were 57 and 94%, respectively, compared to those of clinical examination that were 28 and 100%, respectively, within 24 h following tissue transfer. The sensitivity and specificity of HSI were 63 and 96%, respectively, compared to those of clinical examination that were 63 and 100%, respectively, within the first 72 h. A tissue hemoglobin index of ≥53% could predict venous congestion after free-flap surgery. HSI demonstrated higher sensitivity than clinical examination within the first 24 h; however, it was not superior compared to clinical findings within 72 h.

Into the unknown: expression profiling without genome sequence information in CHO by next generation sequencing.

The arrival of next-generation sequencing (NGS) technologies has led to novel opportunities for expression profiling and genome analysis by utilizing vast amounts of short read sequence data. Here, we demonstrate that expression profiling in organisms lacking any genome or transcriptome sequence information is feasible by combining Illumina's mRNA-seq technology with a novel bioinformatics pipeline that integrates assembled and annotated Chinese hamster ovary (CHO) sequences with information derived from related organisms. We applied this pipeline to the analysis of CHO cells which were chosen as a model system owing to its relevance in the production of therapeutic proteins. Specifically, we analysed CHO cells undergoing butyrate treatment which is known to affect cell cycle regulation and to increase the specific productivity of recombinant proteins. By this means, we identified sequences for >13,000 CHO genes which added sequence information of approximately 5000 novel genes to the CHO model. More than 6000 transcript sequences are predicted to be complete, as they covered >95% of the corresponding mouse orthologs. Detailed analysis of selected biological functions such as DNA replication and cell cycle control, demonstrated the potential of NGS expression profiling in organisms without extended genome sequence to improve both data quantity and quality.

Burn depth assessment using hyperspectral imaging in a prospective single center study.

BACKGROUND: The assessment of thermal burn depth remains challenging. Over the last decades, several optical systems were developed to determine burn depth. So far, only laser doppler imaging (LDI) has been shown to be reliable while others such as infrared thermography or spectrophotometric intracutaneous analysis have been less accurate. The aim of our study is to evaluate hyperspectral imaging (HSI) as a new optical device. METHODS: Patients suffering thermal trauma treated in a burn unit in Germany between November 2019 and September 2020 were included. Inclusion criteria were age ≥18 years, 2nd or 3rd degree thermal burns, written informed consent and presentation within 24 h after injury. Clinical assessment and hyperspectral imaging were performed 24, 48 and 72 h after the injury. Patients in whom secondary wound closure was complete within 21 days (group A) were compared to patients in whom secondary wound closure took more than 21 days or where skin grafting was indicated (group B). Demographic data and the primary parameters generated by HSI were documented. A Mann Whitney-U test was performed to compare the groups. A p-value below 0.05 was considered to be statistically significant. The data generated using HSI were combined to create the HSI burn index (BI). Using a logistic regression and receiver operating characteristics curve (ROC) sensitivity and specificity of the BI were calculated. The trial was officially registered on DRKS (registration number: DRKS00022843). RESULTS: Overall, 59 patients with burn wounds were eligible for inclusion. Ten patients were excluded because of a poor data quality. Group A comprised 36 patients with a mean age of 41.5 years and a mean burnt body surface area of 2.7%. In comparison, 13 patients were allocated to group B because of the need for a skin graft (n = 10) or protracted secondary wound closure lasting more than 21 days. The mean age of these patients was 46.8 years. They had a mean affected body surface area of 4.0%. 24, 48, and 72 h after trauma the BI was 1.0 ± 0.28, 1.2 ± 0.29 and 1.55 ± 0.27 in group A and 0.78 ± 0.14, 1.05 ± 0.23 and 1.23 ± 0.27 in group B. At every time point significant differences were demonstrated between the groups. At 24 h, ROC analysis demonstrated BI threshold of 0.95 (sensitivity 0.61/specificity 1.0), on the second day of 1.17 (sensitivity 0.51/specificity 0.81) and on the third day of 1.27 (sensitivity 0.92/specificity 0.71). CONCLUSION: Changes in microcirculation within the first 72 h after thermal trauma were reflected by an increasing BI in both groups. After 72 h, the BI is able to predict the need for a skin graft with a sensitivity of 92% and a specificity of 71%.

3D-perfusion analysis of burn wounds using hyperspectral imaging.

BACKGROUND: Determination of the depth of burn wounds is still a challenge in clinical practise and fundamental for an optimal treatment. Hyperspectral imaging (HSI) has a high potential to be established as a new contact-free measuring method in medicine. From hyperspectral spectra 3D-perfusion parameters can be estimated and the microcirculatory of burn wounds over the first 72h after thermal injury can be objectively described. METHODS: We used a hyperspectral imaging camera and extended data processing methods to calculate 3D-perfusion parameters of burn wounds from adult patients. The data processing results in the estimation of perfusion parameters like volume fraction and oxygenation of haemoglobin for 6 different layers of the injured skin. The parameters are presented as depth profiles. We analyzed and compared measurements of wounds of different degrees of damage and present the methodology and preliminary results. RESULTS: The depth profiles of the perfusion parameters show characteristic features and differences depending on the degree of damage. With Hyperspectral Imaging and the advanced data processing the perfusion characteristics of burn wounds can be visualized in more detail. Based on the analysis of this perfusion characteristics, a new and better reliable classification of burn degrees can be developed supporting the surgeon in the early selection of the optimal treatment.

Effects of erythropoietin in skin wound healing are dose related.

The hematopoietic growth factor erythropoietin (EPO) attracts attention due to its all-tissue-protective pleiotropic properties. We studied the effect of EPO on dermal regeneration using intravital microscopy in a model of full dermal thickness wounds in the skin-fold chamber of hairless mice. Animals received repetitive low doses or high doses of EPO (RLD-EPO or RHD-EPO) or a single high dose of EPO (SHD-EPO). SHD-EPO accelerated wound epithelialization, reduced wound cellularity, and induced maturation of newly formed microvascular networks. In contrast, RHD-EPO impaired the healing process, as indicated by delayed epithelialization, high wound cellularity, and lack of maturation of microvascular networks. Also, RHD-EPO caused an excessive erythrocyte mass and rheological malfunction, further deteriorating vessel and tissue maturation. Moreover, RHD-EPO altered fibroblast and keratinocyte migration in vitro, while both cell types exposed to RLD-EPO, and, in particular, to SHD-EPO showed accelerated wound scratch closure. In summary, our data show that a single application of a high dose of EPO accelerates and improves skin wound healing.

CHO gene expression profiling in biopharmaceutical process analysis and design.

Increase in both productivity and product yields in biopharmaceutical process development with recombinant protein producing mammalian cells can be mainly attributed to the advancements in cell line development, media, and process optimization. Only recently, genome-scale technologies enable a system-level analysis to elucidate the complex biomolecular basis of protein production in mammalian cells promising an increased process understanding and the deduction of knowledge-based approaches for further process optimization. Here, the use of gene expression profiling for the analysis of a low titer (LT) and high titer (HT) fed batch process using the same IgG producing CHO cell line was investigated. We found that gene expression (i) significantly differed in HT versus LT process conditions due to differences in applied chemically defined, serum-free media, (ii) changed over the time course of the fed batch processes, and that (iii) both metabolic pathways and 14 biological functions such as cellular growth or cell death were affected. Furthermore, detailed analysis of metabolism in a standard process format revealed the potential use of transcriptomics for rational media design as is shown for the case of lipid metabolism where the product titer could be increased by about 20% based on a lipid modified basal medium. The results demonstrate that gene expression profiling can be an important tool for mammalian biopharmaceutical process analysis and optimization.

[Hyperspectral imaging for postoperative flap monitoring of pedicled flaps]. / Hyperspektralimaging zum postoperativen Lappenmonitoring von lokoregionären Lappenplastiken.

BACKGROUND: Since pedicle flaps were first described by the Indian physician Sushruta Samhita in the 6th century B. C., they have become an integral part of reconstructive surgery. As more and more research has been conducted into the underlying physical principles, flap monitoring has developed steadily in the last few decades. Hyperspectral Imaging (HSI) is a new quantitative measuring method for assessing the perfusion of the underlying tissue. OBJECTIVE: This study aims to evaluate HSI as a monitoring method for pedicle flaps. PATIENTS AND METHODS: In 16 patients who had undergone reconstructive surgery, oxygen saturation, haemoglobin and water concentration of the locoregional flap, necrotic flap areas as well as intact skin were measured on postoperative days 1 to 7. Subsequently, the data were statistically described and graphically illustrated. RESULTS: HSI revealed increased haemoglobin concentration and decreased oxygen and water concentration in necrotic flap areas compared with the monitor island and healthy skin. The distribution of the values collected from the vital skin areas and the monitor island was almost identical. CONCLUSION: HSI allows for safe, immediate, non-contact measurement of tissue perfusion of transferred tissue areas in patients after pedicle flap surgery. The use of HSI may improve postoperative flap monitoring.

Consequences of surgical stress on the kinetics of skin wound healing: partial hepatectomy delays and functionally alters dermal repair.

The objective was to determine the significance of surgical trauma in dermal wound healing. Using intravital microscopy, we analyzed the healing kinetics of full-thickness dermal wounds in the ears of SKH1 mice. Partial hepatectomy (pHx) simulated major surgical trauma, while laparotomy only served as a sham operation (sham). Animals without abdominal surgery served as controls (control). Laparotomy wounds were analyzed for biomechanical qualities and collagen deposition. Morphological characterization of skin repair was performed by histology/immunohistochemistry. In vitro cell assays assessed the paracrine effects of surgical stress. PHx caused a transient increase in tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 levels and led to weight loss, reflecting the host's overall response to surgery. Wound closure in pHx animals was delayed vs. control and sham animals, as indicated by significantly lower values of epithelialization and neovascularization over 10 days. Ear wound histology further revealed a provisional wound matrix with a reduced microvessel density. Moreover, pHx-laparotomy wounds showed a reduced bursting strength coexisting with significantly decreased collagen content. PHx and sham serum caused a significant alteration in in vitro fibroblast viability. Skin healing is dependent on the extent of surgery and is influenced by its paracrine effects. Therefore, considerable effort should be focused on the development of strategies limiting surgery-associated perturbations of dermal repair.

Sex-specific and inter-individual differences in biomarkers of selenium status identified by a calibrated ELISA for selenoprotein P.

Selenoprotein P (SELENOP) is a liver-derived transporter of selenium (Se) in blood, and a meaningful biomarker of Se status. Se is an essential trace element for the biosynthesis of enzymatically-active selenoproteins, protecting the organism from oxidative damage. The usage of uncalibrated assays hinders the comparability of SELENOP concentrations and their pathophysiological interpretation across different clinical studies. On this account, we established a new sandwich SELENOP-ELISA and calibrated against a standard reference material (SRM1950). The ELISA displays a wide working range (11.6-538.4µg/L), high accuracy (2.9%) and good precision (9.3%). To verify whether SELENOP correlates to total Se and to SELENOP-bound Se, serum samples from healthy subjects and age-selected participants from the Berlin Aging Study II were analyzed by SELENOP-ELISA and Se quantification. SELENOP was affinity-purified and its Se content was determined from a subset of samples. There was a high correlation of total Se and SELENOP concentrations in young and elderly men, and in elderly women, but not in young women, indicating a specific sexual dimorphism in these biomarkers of Se status in young subjects. The Se content of isolated SELENOP was independent of sex and age (mean±SD: 5.4±0.5). By using this calibrated SELENOP-ELISA, prior reports on pathological SELENOP concentrations in diabetes and obesity are challenged as the reported values are outside reasonable limits. Biomarkers of Se status in clinical research need to be measured by validated assays in order to avoid erroneous data and incorrect interpretations, especially when analyzing young women. The Se content of circulating SELENOP differs between individuals and may provide some important diagnostic information on Se metabolism and status.

Whole-Genome Sequence of Bradyrhizobium elkanii Strain UASWS1016, a Potential Symbiotic Biofertilizer for Agriculture.

Bradyrhizobium elkanii UASWS1016 has been isolated from a wet oxidation sewage plant in Italy. Fully equipped for ammonia assimilation, heavy metal resistances, and aromatic compounds degradation, it carries a large type IV secretion system, specific of plant-associated microbes. Deprived of toxins, it could be considered for agricultural and environmental uses.