Risk factors of major complications after flap surgery in the treatment of stage III and IV pressure injury in people with spinal cord injury/disorder: a retrospective cohort study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To identify risk factors associated with major complications after flap surgery in people with spinal cord injury or disorder (SCI/D) and stage III and IV pressure injury (PI). SETTING: Swiss hospital specialized in the treatment of people with SCI/D using the Basel Decubitus Approach. METHODS: We examined 60 risk factors for major postoperative complications in PIs over sacrum/coccyx, ischium or trochanter between 01/2016 and 12/2021. We performed descriptive analysis and computed global p-values using likelihood ratio tests adjusted for clustering of PIs in individuals. RESULTS: We included 220 PI treatment procedure from 149 individuals. The study population consisted of 163 (74%) men, 133 (60%) traumatic SCI, 136 (58%) stage IV PI, 198 (90%) individuals with paraplegia, 93 (42%) with osteomyelitis, and 85 (39%) with recurrent PI. Major complications 42 (19%) occurred more often in individuals with stage IV PI (p < 0.01), individuals without osteomyelitis (p < 0.03), and individuals with pathological blood concentrations of cystatin c (p < 0.028), calcium (p < 0.048), and vitamin B12 (p < 0.0049) as well as normal blood concentrations of HbA1c (p < 0.033). Immobilization (p < 0.0089) and hospital stay (p < 0.0001) of individuals with major complications was longer. CONCLUSION: In the Basel Decubitus Approach, stage IV PI, absence of osteomyelitis, reduced vitamin B12 and calcium, elevated cystatin c, and normal HbA1c should be addressed to reduce major complications.

[Interoperability Working Group: core dataset and information systems for data integration and data exchange in the Medical Informatics Initiative]. / Arbeitsgruppe Interoperabilität: Kerndatensatz und Informationssysteme für Integration und Austausch von Daten in der Medizininformatik-Initiative.

The interoperability Working Group of the Medical Informatics Initiative (MII) is the platform for the coordination of overarching procedures, data structures, and interfaces between the data integration centers (DIC) of the university hospitals and national and international interoperability committees. The goal is the joint content-related and technical design of a distributed infrastructure for the secondary use of healthcare data that can be used via the Research Data Portal for Health. Important general conditions are data privacy and IT security for the use of health data in biomedical research. To this end, suitable methods are used in dedicated task forces to enable procedural, syntactic, and semantic interoperability for data use projects. The MII core dataset was developed as several modules with corresponding information models and implemented using the HL7® FHIR® standard to enable content-related and technical specifications for the interoperable provision of healthcare data through the DIC. International terminologies and consented metadata are used to describe these data in more detail. The overall architecture, including overarching interfaces, implements the methodological and legal requirements for a distributed data use infrastructure, for example, by providing pseudonymized data or by federated analyses. With these results of the Interoperability Working Group, the MII is presenting a future-oriented solution for the exchange and use of healthcare data, the applicability of which goes beyond the purpose of research and can play an essential role in the digital transformation of the healthcare system.

Molecular characterization of chronic cutaneous wounds reveals subregion- and wound type-specific differential gene expression.

A limited understanding of the pathology underlying chronic wounds has hindered the development of effective diagnostic markers and pharmaceutical interventions. This study aimed to elucidate the molecular composition of various common chronic ulcer types to facilitate drug discovery strategies. We conducted a comprehensive analysis of leg ulcers (LUs), encompassing venous and arterial ulcers, foot ulcers (FUs), pressure ulcers (PUs), and compared them with surgical wound healing complications (WHCs). To explore the pathophysiological mechanisms and identify similarities or differences within wounds, we dissected wounds into distinct subregions, including the wound bed, border, and peri-wound areas, and compared them against intact skin. By correlating histopathology, RNA sequencing (RNA-Seq), and immunohistochemistry (IHC), we identified unique genes, pathways, and cell type abundance patterns in each wound type and subregion. These correlations aim to aid clinicians in selecting targeted treatment options and informing the design of future preclinical and clinical studies in wound healing. Notably, specific genes, such as PITX1 and UPP1, exhibited exclusive upregulation in LUs and FUs, potentially offering significant benefits to specialists in limb preservation and clinical treatment decisions. In contrast, comparisons between different wound subregions, regardless of wound type, revealed distinct expression profiles. The pleiotropic chemokine-like ligand GPR15L (C10orf99) and transmembrane serine proteases TMPRSS11A/D were significantly upregulated in wound border subregions. Interestingly, WHCs exhibited a nearly identical transcriptome to PUs, indicating clinical relevance. Histological examination revealed blood vessel occlusions with impaired angiogenesis in chronic wounds, alongside elevated expression of genes and immunoreactive markers related to blood vessel and lymphatic epithelial cells in wound bed subregions. Additionally, inflammatory and epithelial markers indicated heightened inflammatory responses in wound bed and border subregions and reduced wound bed epithelialization. In summary, chronic wounds from diverse anatomical sites share common aspects of wound pathophysiology but also exhibit distinct molecular differences. These unique molecular characteristics present promising opportunities for drug discovery and treatment, particularly for patients suffering from chronic wounds. The identified diagnostic markers hold the potential to enhance preclinical and clinical trials in the field of wound healing.

Effect of a computerized decision support system on the treatment approach of stage III or IV pressure injury in patients with spinal cord injury: a feasibility study.

BACKGROUND: Stage III and IV pressure injuries (PIs) in patients with spinal cord injury (SCI) require complex interdisciplinary and interprofessional treatment approaches that are difficult to implement. Practical aspects, such as information exchange and coordination, remain challenging. We investigated whether a computerized decision support system (CDSS) could increase treatment adherence and improve clinical outcomes and interprofessional collaboration. METHOD: In this feasibility study, a core team developed the initial treatment process and adapted it based on several discussions with clinical experts and information technologists. The CDSS followed the Basel Decubitus Approach and was used in a clinic specializing in SCI. Thirty patients with SCI admitted for stage III/IV PI between July 2016 and May 2017 were randomly allocated to standard or CDSS-supported care. Between-group differences in treatment adherence, complication rates, length of stay, and costs were analyzed using descriptive statistics. The use of the CDSS and potential barriers and facilitators were evaluated through interprofessional focus groups, transcribed verbatim, and thematically analyzed (30 participants). RESULTS: No differences in SCI characteristics, comorbidities, or PI characteristics (localization: ischium [number (n) = 19 PI, 63%], sacrum [n = 10 PI, 33%], recurrent PI [n = 21, 70%]) were found between the two groups. Furthermore, no statistically significant differences were observed in treatment adherence, frequency of major (20% vs. 13% between CDSS and control group) and minor (33% vs 27%) complications, and length of stay (98 [±28] vs 81 [±23] days). Healthcare professionals found the CDSS to be helpful for visualizing the treatment process. However, the high workload and difficulties in the information technology processes, such as missing reminders, slow computer performance and data processing, and poor accessibility, hindered the effective implementation of the CDSS. CONCLUSION: The implementation of the CDSS to support the treatment of stage III/IV PI in patients with SCI was feasible and included definitions of milestones, interventions, and outcomes. However, to assess the impact of the CDSS, a longer observation period is required. Further, the technical difficulties must be addressed, and solid integration of the CDSS into the clinical information system is necessary. TRIAL REGISTRATION: This quality improvement project received a declaration of no objection from the Ethics Committee of Northwest and Central Switzerland (EKNZ UBE-16/003), and ethical approval was received for the focus groups (EKNZ Req-2017-00860).

Risk constellation of hospital acquired pressure injuries in patients with a spinal cord injury/ disorder - focus on time since spinal cord injury/ disorder and patients' age.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: The aim of this study was to evaluate how time since spinal cord injury/disorder (SCI/D) and patients' age influence risk constellation for hospital acquired pressure injuries (HAPI) in patients with a SCI/D. SETTING: Acute care and rehabilitation clinic specialized in SCI/D. METHODS: We collected patients' characteristics and 85 risk factors for HAPI development in adults with SCI/D with at least one HAPI during their inpatient stay between August 2018 and December 2019. We analyzed patients' characteristics and HAPI risk factors using descriptive statistics according to time since SCI/D ( < 1 year, 1-15 years, > 15 years) and patients' age (18-35 years, 35-65 years, > 65 years). RESULTS: We identified 182 HAPI in 96 patients. Comparing patients with SCI/D < 1 year with the other groups, autonomic dysreflexia (p < 0.001), abnormal body temperature (p = 0.001), hypertensive episode (p = 0.005), and pneumonia (p < 0.001) occurred more frequently; mean hemoglobin (p < 0.001), albumin (p = 0.002) and vitamin D levels (p = 0.013) were significantly lower, and patients with time since SCI/D < 1 year scored fewer points (10-12) on the Braden Scale (p < 0.001). Comparing groups per patients' age, only the SCIPUS score was higher in patients > 65 years compared to the other two groups (p = 0.002). CONCLUSIONS: Different risk factor constellation seem to be underlying HAPI development with more differences in patients time since SCI/D than patients' age. Awareness of these differences in risk factor constellation depending on time since SCI/D in these patients might lead to different HAPI prevention strategies. SPONSORSHIP: The study team didn't receive any additional sponsorship.

Osteomyelitis and antibiotic treatment in patients with grade IV pressure injury and spinal cord lesion-a retrospective cohort study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To analyze characteristics and treatment of osteomyelitis (OM) in the treatment of grade IV pressure injury (PI) in patients with spinal cord injury/disorder (SCI/D) following the Basel Decubitus Concept. SETTING: Acute care and rehabilitation clinic specialized in SCI/D. METHODS: Patients with SCI/D were admitted for grade IV PI treatment between 1st January 2010 and 28th February 2015. Patients, SCI/D, and PI characteristics were collected from chart reviews. Descriptive statistics and differences between groups with and without OM were evaluated. RESULTS: In total, 117 patients (87 male, 30 female) with 130 PI grade IV were included. In 95 patients (81%), OM was diagnosed histologically. In 87 cases, more than one bacterial species was involved. Out of 49 different bacterial species, Enterococcus faecalis and Staphylococus aureus were most frequently observed. Amoxicillin/clavulanic acid and ciprofloxacin were the most frequently used out of 24 different antibiotics. Length of antibiotic treatment varied between <8 days and >91 days with 31 patients receiving antibiotics for about 8 weeks. Complications occurred in all groups of antibiotic duration. Having a paraplegia, no OM and sacral PI was associated with increased complication rates, but the number of patients did not allow comprehensive risk factor analysis. CONCLUSION: Because the variety of patients concerning SCI/D, PI, and OM characteristics did not show a conclusive relation between length of antibiotic treatment and complication rates, the development of a subgroup specific treatment concept for PI in patients with SCI/D would be favorable to further optimize antibiotic treatment.

Risk factors for hospital acquired pressure injury in patients with spinal cord injury during first rehabilitation: prospective cohort study.

STUDY DESIGN: Prospective observational cohort study. OBJECTIVES: First, describe pressure injury (PI) and associated risk factors in individuals with spinal cord injury/disorder (SCI/D) during first rehabilitation. Second, evaluate a prediction model for hospital acquired PI (HAPI) development. SETTING: Acute care and rehabilitation clinic specialized in SCI/D. METHODS: Patients ≥18 years of age with SCI/D were included during first rehabilitation between 08/2018 and 12/2019. We performed a systematic literature search to identify risk factors for PI development. Patients were classified according to HAPI developed. Between group differences of patients' characteristics and risk factors were analyzed using descriptive statistics. Logistic predictive models were performed to estimate HAPI development and receiver operator characteristic (ROC) curve was used to test the model. RESULTS: In total, 94 patients were included, 48 (51.1%) developed at least one HAPI and in total 93 were observed, mainly stage I and stage II HAPI according to the European Pressure Ulcer Advisory Panel. We found nine significantly associated risk factors: completeness of SCI/D, pneumonia, sedative medications, autonomic dysreflexia, Braden ≤12 points, SCIPUS ≥9 points, lower admission SCIM and lower admission FIM-cognition, longer length of stay (LOS) (p ≤ 0.0005). In a predictive model, none of the risk factors was associated with HAPI development (AUC = 0.5). CONCLUSION: HAPIs in patients with SCI/D during first rehabilitation are a frequent and complex condition and associated with several risk factors. No predictive model exists but with the identified risk factors of this study, larger studies can create a tailored and flexible HAPI risk prediction model.

Changes in skin-physiology after local heat application using two different methods in individuals with complete paraplegia: a feasibility and safety trial.

STUDY DESIGN: Interventional feasibility study. OBJECTIVES: To evaluate safety and effects of local heat preconditioning on skin physiology using water-filtered infrared-A radiation (wIRA) or warm water therapy (wWT) in individuals with spinal cord injury (SCI). SETTING: Acute and rehabilitation center, specialized in SCI. METHODS: A convenience sample of 15 individuals (3 women, 12 men) with complete paraplegia from thoracic levels ranging between T2 and T12 received local heat applications either with wIRA or wWT on the thigh (paralyzed area) and on the upper arm (non-paralyzed area). Local heat was applied during three 30-min cycles, each separated by 30 min rest; thus, the treatment lasted for 180 min. Temperature, blood perfusion, and skin redness were measured at baseline, before and after heat application and 24 h after the last application. RESULTS: Heat applications with wIRA and wWT were well-tolerated. No burns or any other side effects were detected. Skin temperature (p ≤ 0.008) and blood perfusion (p ≤ 0.013) significantly increased after heat application. Local skin temperature (arm p = 0.004/leg p < 0.001) and blood perfusion (arm p = 0.011/leg p = 0.001) after the first and the second application cycle, respectively, were significantly higher during heat application with wIRA than with wWT. However, skin redness did not change significantly (p = 0.1). No significant differences were observed between the paralyzed and non-paralyzed areas for all parameters immediately, as well as 24 h after the treatment. CONCLUSIONS: Although both heating methods have been confirmed as safe treatments in this study, further investigations with regard to their efficacy in the context of preconditioning are warranted. SPONSORSHIP: The use of the instruments Hydrosun® 750 Irradiator (Hydrosun Medizintechnik, Germany) and Hilotherm-Calido 6 (Hilotherm GmbH, Germany) was sponsored by the Dr. med. h. c. Erwin Braun Foundation and by Hilotherm GmbH, respectively.

Extending the limits of the anterior tibial artery as the recipient vessel for around the knee and proximal lower extremity defect reconstruction using the free anterolateral thigh and gracilis flap.

PURPOSE: The aim is to describe a technique with orthograde dissection of the anterior tibial artery (ATA) used as the recipient vessel for the end-to-end (ETE) anastomosis in defect reconstruction around the knee and for proximal/middle third leg defects with free anterolateral thigh (ALT) and gracilis flaps. PATIENTS AND METHODS: Between March 2009 and May 2014, 22 patients undergoing lower extremity reconstruction were evaluated. Of those, 4 patients were included. The locations of injury were 3 defects around the knee and 1 defect at the proximal and middle third of the lower leg (mean defect size 18 x 8.5 cm and a range of 17-20 x 5-10 cm). There were 2 cases after trauma and 2 cases with infection. Two free gracilis and 2 free ALT flaps were performed of equal size to the defects. The mean flap pedicle length was 11 cm (range of 7-16 cm) and the mean length of the mobilized recipient vessels was 10.5 cm (range of 6-14 cm). RESULTS: One flap loss (ALT) occurred, requiring a salvage procedure with a latissimus dorsi flap, whereas wound dehiscence at the donor site and a hematoma below the ALT flap was observed in 2 cases, requiring small revision. After a mean follow-up of 52 months (range of 38-87 months), there was stable soft tissue coverage in all patients. CONCLUSION: By orthograde dissection of the ATA, an adequate vessel length and size may be achieved, improving arc of rotation to successfully cover more distant defects.

Nipple Reconstruction After Autologous or Expander Breast Reconstruction: A Multimodal and 3-Dimensional Analysis.

BACKGROUND: Little is known about the influence of the underlying tissue as donor for nipple-areola complex (NAC) reconstruction. Also, there is a complete lack of knowledge about the fate of nipple volume. OBJECTIVES: The goal of this retrospective, single-institution study was to analyze a case series after nipple reconstruction using a multimodal evaluation including 3-dimensional (3D) laser scanner analyses. METHODS: Unilateral mastectomy patients after either expander-based or autologous breast reconstruction using the skate flap were included. NAC caliper measurement of nipple and areola size was performed. 3D laser scanner analysis (Minolta Vivid 900) was used to calculate nipple volume, measurement of nipple, and areolar projection and diameter. Sensitivity was evaluated using the Semmes Weinstein test and patient satisfaction by a visual analog scale (VAS 1-10). RESULTS: A total of 10 patients were included in the expander group and 12 patients were included in the flap group. After a median follow-up period of 32 months in the expander group and 34 months in the flap group, non-contact 3D laser surface scanning revealed a difference in projection of 55 to 60% compared to the contralateral side. The contraction in all 3 dimensions led to a dramatic difference in nipple volume with 12 ± 8% (flap reconstructions) and 12 ± 7% (expander reconstructions). Sensitivity of the areola showed better values after expander-based reconstruction. Despite the significant discrepancy in nipple volume and projection as well as areolar diameter, overall patient satisfaction was acceptable (VAS 4.1 ± 3.5). CONCLUSIONS: Volume assessment revealed a massive asymmetry to the intact nipple but not between expander and flap reconstructions. Although asymmetry of the areola and nipple remains, patient satisfaction is acceptable. LEVEL OF EVIDENCE 4.

Phase II metabolism in human skin: skin explants show full coverage for glucuronidation, sulfation, N-acetylation, catechol methylation, and glutathione conjugation.

Although skin is the largest organ of the human body, cutaneous drug metabolism is often overlooked, and existing experimental models are insufficiently validated. This proof-of-concept study investigated phase II biotransformation of 11 test substrates in fresh full-thickness human skin explants, a model containing all skin cell types. Results show that skin explants have significant capacity for glucuronidation, sulfation, N-acetylation, catechol methylation, and glutathione conjugation. Novel skin metabolites were identified, including acyl glucuronides of indomethacin and diclofenac, glucuronides of 17ß-estradiol, N-acetylprocainamide, and methoxy derivatives of 4-nitrocatechol and 2,3-dihydroxynaphthalene. Measured activities for 10 µM substrate incubations spanned a 1000-fold: from the highest 4.758 pmol·mg skin(-1)·h(-1) for p-toluidine N-acetylation to the lowest 0.006 pmol·mg skin(-1)·h(-1) for 17ß-estradiol 17-glucuronidation. Interindividual variability was 1.4- to 13.0-fold, the highest being 4-methylumbelliferone and diclofenac glucuronidation. Reaction rates were generally linear up to 4 hours, although 24-hour incubations enabled detection of metabolites in trace amounts. All reactions were unaffected by the inclusion of cosubstrates, and freezing of the fresh skin led to loss of glucuronidation activity. The predicted whole-skin intrinsic metabolic clearances were significantly lower compared with corresponding whole-liver intrinsic clearances, suggesting a relatively limited contribution of the skin to the body's total systemic phase II enzyme-mediated metabolic clearance. Nevertheless, the fresh full-thickness skin explants represent a suitable model to study cutaneous phase II metabolism not only in drug elimination but also in toxicity, as formation of acyl glucuronides and sulfate conjugates could play a role in skin adverse reactions.

Impact of platelet rich plasma and adipose stem cells on lymphangiogenesis in a murine tail lymphedema model.

BACKGROUND: Lymphedema is an underdiagnosed pathology which in industrialized countries mainly affects cancer patients that underwent lymph node dissection and/or radiation. Currently no effective therapy is available so that patients' life quality is compromised by swellings of the concerned body region. This unfortunate condition is associated with body imbalance and subsequent osteochondral deformations and impaired function as well as with an increased risk of potentially life threatening soft tissue infections. METHODS: The effects of PRP and ASC on angiogenesis (anti-CD31 staining), microcirculation (Laser Doppler Imaging), lymphangiogenesis (anti-LYVE1 staining), microvascular architecture (corrosion casting) and wound healing (digital planimetry) are studied in a murine tail lymphedema model. RESULTS: Wounds treated by PRP and ASC healed faster and showed a significantly increased epithelialization mainly from the proximal wound margin. The application of PRP induced a significantly increased lymphangiogenesis while the application of ASC did not induce any significant change in this regard. CONCLUSIONS: PRP and ASC affect lymphangiogenesis and lymphedema development and might represent a promising approach to improve regeneration of lymphatic vessels, restore disrupted lymphatic circulation and treat or prevent lymphedema alone or in combination with currently available lymphedema therapies.

Local flap therapy for the treatment of pressure sore wounds.

The aim of this study was to analyse the effectiveness of an interdisciplinary cooperation between conservative and surgical disciplines for the treatment of pressure sores (PS). From January 2004 to December 2005, a single-centre study was performed with paraplegic and tetraplegic patients presenting with PS grades III-V. Outcome measures were defect size, grade, method of reconstruction, complication and recurrence rate as well as average length of hospitalisation. A total of 119 patients aged 22-84 years with totally 170 PS were included. The most common PS were located in the ischial region (47%), followed by the sacral (18%), trochanteric (11%), foot (9%) and the malleolar (8%) regions. Defect sizes ranged between 4 and 255 cm(2) . Grade IV was the most common PS (68%), followed by grade III (30%) and grade V (2%) PS. For wound closure, fasciocutaneous flaps were used most frequently (71%), followed by skin grafts (10%) and myocutaneous flaps (7%). Postoperative follow-up ranged between 6 and 38 months. The overall complication and recurrence rate was 26% and 11%, respectively. If no complication occurred, the average duration of hospitalisation stay after the first debridement was 98 ± 62 days. In conclusion, our treatment concept is reliable, effective and results in a low recurrence rate. The complication rate, even though favourable when compared with the literature, still needs to be improved.

Aldehyde oxidase activity in fresh human skin.

Human aldehyde oxidase (AO) is a molybdoflavoenzyme that commonly oxidizes azaheterocycles in therapeutic drugs. Although high metabolic clearance by AO resulted in several drug failures, existing in vitro-in vivo correlations are often poor and the extrahepatic role of AO practically unknown. This study investigated enzymatic activity of AO in fresh human skin, the largest organ of the body, frequently exposed to therapeutic drugs and xenobiotics. Fresh, full-thickness human skin was obtained from 13 individual donors and assayed with two specific AO substrates: carbazeran and zoniporide. Human skin explants from all donors metabolized carbazeran to 4-hydroxycarbazeran and zoniporide to 2-oxo-zoniporide. Average rates of carbazeran and zoniporide hydroxylations were 1.301 and 0.164 pmol⋅mg skin(-1)⋅h(-1), resulting in 13 and 2% substrate turnover, respectively, after 24 hours of incubation with 10 µM substrate. Hydroxylation activities for the two substrates were significantly correlated (r(2) = 0.769), with interindividual variability ranging from 3-fold (zoniporide) to 6-fold (carbazeran). Inclusion of hydralazine, an irreversible inhibitor of AO, resulted in concentration-dependent decrease of hydroxylation activities, exceeding 90% inhibition of carbazeran 4-hydroxylation at 100 µM inhibitor. Reaction rates were linear up to 4 hours and well described by Michaelis-Menten enzyme kinetics. Comparison of carbazeran and zoniporide hydroxylation with rates of triclosan glucuronidation and sulfation and p-toluidine N-acetylation showed that cutaneous AO activity is comparable to tested phase II metabolic reactions, indicating a significant role of AO in cutaneous drug metabolism. To our best knowledge, this is the first report of AO enzymatic activity in human skin.

Laser scanning evaluation of atrophy after autologous free muscle transfer.

Denervated muscle tissue undergoes morphologic changes that result in atrophy. The amount of muscle atrophy after denervation following free muscle transfer has not been measured so far. Therefore, the amount of muscle atrophy in human free muscle transfer for lower extremity reconstruction was measured in a series of 10 patients. Three-dimensional laser surface scanning was used to measure flap volume changes 2 weeks as well as 6 and 12 months after the operation. None of the muscles transferred was re-innervated.All muscles healed uneventfully without signs of compromised perfusion resulting in partial flap loss. The muscle volume decreased to 30 ± 4% and 19 ± 4% 6 and 12 months, respectively, after the operation, ie, the volume decreased by approximately 80% within a 12-month period.Denervated free muscle flap tissue undergoes massive atrophy of approximately 80%, mostly within the first 6 months.

Second free radial forearm flap for urethral reconstruction after partial flap necrosis of tube-in-tube phalloplasty with radial forearm flap: a report of two cases.

We present a salvage procedure to reconstruct the neo-urethra after partial flap necrosis occurring in free radial forearm flap (RFF) phalloplasty for sex reassignment surgery. Two cases of tube-in-tube phalloplasty using a free sensate RFF are described in which partial flap necrosis occurred involving the complete length of the neo-urethra and a strip of the outer lining of the neo-phallus. Neo-urethra-reconstruction was performed with a second RFF from the contralateral side providing well-vascularized tissue. No flap-related complications were observed. Twelve months postoperatively, both patients were able to void while standing. A satisfactory aesthetic appearance of the neo-phallus could be preserved with an excellent tactile and erogenous sensitivity. Using this technique, we successfully salvaged the neo-urethra and reconstructed the outer lining of the neo-phallus

Interoperability Is a Process - The Data Sharing Framework.

Common syntax and data semantics are core components of healthcare interoperability standards. However, interoperable data exchange processes are also needed to enable the integration of existing systems between organizations. While solutions for healthcare delivery processes are available and have been widely adopted, support for processes targeting bio-medical research is limited. Our Data Sharing Framework creates a platform to implement research processes like cohort size estimation, reviews and approvals of research proposals, consent checks, record linkage, pseudonymization and data sharing across organizations. The described framework implements a distributed business process engine for executing BPMN 2.0 processes with synchronization and data exchange using FHIR R4 resources. Our reference implementation has been rolled out to 38 organizations across three research consortia in Germany and is available as open source under the Apache 2.0 license.

Long-term preconditioning with erythropoietin reduces ischemia-induced skin necrosis.

OBJECTIVE: Recent findings have attested to EPO tissue-protective effects in ischemically challenged tissues. Therefore, the study aimed at elaborating the effect of systemic pre- and postconditioning using EPO in a mouse model of persistent ischemia of the skin. METHODS: Three groups of nine C57Bl/6-mice each were analyzed. The experimental groups consisted of untreated controls, EPO preconditioning, and EPO postconditioning (500 IU EPO/kg bw/day for 10 days). Critically perfused skin flaps undergoing necrosis, if kept untreated, were mounted into dorsal skinfold chambers. Intravital epi-fluorescence microscopy was performed for 10 days to assess tissue necrosis, microcirculation, inflammation, and angiogenesis. Protein expression analysis of eNOS was performed. Hematocrit analyses were carried out separately in eight animals. RESULTS: Only EPO preconditioning was able to significantly reduce necrosis, when compared with controls. This correlated with a significantly increased CD in the critically perfused tissue. Administration of EPO only slightly increased eNOS expression at day 10, when compared with controls. EPO induced angiogenesis and increased hematocrit. Finally, EPO significantly reduced leukocytic inflammation in arterioles in all EPO receiving mice. CONCLUSIONS: EPO preconditioning effectively reduces skin necrosis predominantly by capillary maintenance and reperfusion, as well as improved tissue regeneration. Thus, EPO preconditioning might represent a promising, non-invasive approach to reduce complications in ischemically challenged skin.

Secondary burn progression decreased by erythropoietin.

OBJECTIVE: To investigate whether systemic erythropoietin administration can prevent secondary burn progression in an experimental model and to elucidate the underlying mechanisms. DESIGN: Prospective study. SETTING: University-based laboratory research. SUBJECTS: Twenty-one male Wistar rats. INTERVENTIONS: The burn comb model creates four rectangular burned surfaces that are intercalated by three unburned zones (interspaces) prone to secondary necrosis. Twenty-one animals were randomized to three experimental groups: 1) Local cooling with water for 20 minutes (control, 17°C); 2) and 3) local cooling with water and intraperitoneal erythropoietin once a day for five days starting 45 minutes after burn injury (500 IU/kg body weight: EPO 500 or 2500 IU/kg body weight: EPO 2500). MEASUREMENTS AND MAIN RESULTS: Secondary burn progression-both in depth (histology) and in surface (planimetry)-as well as interspace perfusion (laser Doppler flowmetry) and hematocrit were analyzed. Further, dilatory response (inducible nitric oxide synthase expression), inflammation (leukocyte count), and angiogenesis (CD31 expression) were assessed. Finally, wound healing time and contracture rate were reported. Burn progression resulted in complete dermal destruction as well as in important interspace necrosis in control animals, whereas burn progression was significantly reduced in a dose-dependent manner in animals treated with erythropoietin. Tissue protection was associated with an increased interspace perfusion with EPO 500, but not with EPO 2500, and was paralleled by a significant increase in inducible nitric oxide synthase expression and decreased inflammation, independent of the erythropoietin dosage. EPO 2500 led to a significant increase of hematocrit at day 4. Finally, faster wound healing and less contracture were observed in animals treated with EPO 500 only. CONCLUSIONS: Erythropoietin represents an easy-to-use therapeutic approach to prevent secondary burn progression, i.e., to control damage after burn injury. It preserves microcirculatory perfusion within the endangered areas in a dose-dependent manner.

Local shockwave-induced capillary recruitment improves survival of musculocutaneous flaps.

BACKGROUND: Shockwave (SW) application has been shown to limit flap necrosis. However, the underlying microhemodynamic mechanisms remain unclear. Therefore, the objective of this study was to analyze the effect of SW application on a microcirculatory level. METHODS: We treated 12 C57BL/6 mice with local SW application (500 shockwave impulses at 0.15 mJ/mm(2)) either 24 h before (preconditioning [PRE]) or 30 min after (postconditioning [POST]) flap elevation. Animals with an untreated flap (CON) or without a flap served as controls. We applied dorsal skinfold chambers to the animals and performed epifluorescence microscopy over a 10-d period to assess microcirculatory parameters (arteriolar diameter, red blood cell velocity, blood flow, functional capillary density, and intercapillary distance) as well as inflammation, apoptotic cell death, and necrosis. RESULTS: SW application significantly decreased tissue necrosis independently of the application time point (PRE: 29% ± 7%; POST: 25% ± 7% versus CON: 47% ± 2%; day 10, P < 0.05). Arteriolar diameter, red blood cell velocity, and blood flow were not statistically significantly different among the 3 flap groups. However, SW (PRE and POST) resulted in an early and persistent increase in functional capillary density and consequently decreased intercapillary distance compared with CON and the group without a flap (P < 0.05). Also, SW resulted in a significantly decreased inflammatory response (P < 0.05) and induced an angiogenic response, as indicated by new functional microvessel formation observed 5 d after therapy. CONCLUSIONS: Local SW application improved tissue survival by recruitment of sleeping capillaries within the non ischemic tissue and maintenance of capillary perfusion within the critically perfused tissue after induction of ischemia, which was independent of the application time point. Neoangiogenesis occurred beyond the ischemic tolerance of the tissue, and therefore does not seem to contribute to improved tissue survival.