Wnt3a and ASCs are capable of restoring mineralization in staph aureus-infected primary murine osteoblasts.

INTRODUCTION: Bone infections are one of the main reasons for impaired bone regeneration and non-union formation. In previous experimental animal studies we could already demonstrate that bone defects due to prior infections showed a markedly reduced healing capacity, which could effectively be enhanced via application of Wnt3a and Adipose-derived stromal cells (ASCs). For a more in-depth analysis, we investigated proliferation and mineralization of cultured osteoblasts infected with staph aureus and sought to investigate effects of Wnt3a and ASCs on infected osteoblasts. MATERIALS AND METHODS: Primary murine osteoblasts were isolated from calvariae and infected with staph aureus. Infected osteoblasts received treatment via application of recombinant Wnt3a, ASC conditioned medium and were furthermore cocultured with ASCs. Osteoblasts were evaluated by Alamar blue assay for metabolic activity, TUNEL-assay for apoptosis, ALP and Alizarin Red staining for mineralization. In addition, immunoflourescent staining (IF) and qRT-PCR analyses were performed. RESULTS: Infected osteoblasts showed a markedly reduced ability for mineralization and increased apoptosis, which could be restored to physiological levels by Wnt3a and ASC treatment. Interestingly, metabolic activity of osteoblasts seemed to be unaffected by staph aureus infection. Additional analyses of Wnt-pathway activity revealed effective enhancement of canonical Wnt-pathway activity in Wnt3a-treated osteoblasts. CONCLUSIONS: In summary, we gained further osteoblast-related insights into pathomechanisms of reduced bone healing capacity upon infections.

[Moschella island flap for coverage of thumb defects]. / Homodigitaler Insellappen nach Moschella zur Defektdeckung am Daumen.

OBJECTIVE: The homodigital island flap according to Moschella is used to cover palmar and radiodorsal soft tissue defects of the thumb. INDICATIONS: Soft tissue reconstruction of the thumb with exposed bone and/or tendon if reconstruction of the soft tissue is required. CONTRAINDICATIONS: Extensive scars in the harvesting area of the flap; vascular occlusions of the radial artery. SURGICAL TECHNIQUE: After Doppler sonographic imaging of the origin of the vessel radially at the thumb, the pivot point is determined. The flap is then cut from ulnar to radial, including the dorsoradial artery of the thumb. Removal of the origin of the vessel from the radial artery in the tabatiére and preparation from proximal to distal to the pivot point of the flap at the junction of the artery with the palmar vessels. If necessary, a part of the skin can remain palmar to the pivot point to improve venous drainage. The donor site of the flap can primarily close defect sizes up to 5â€¯× 4 cm. POSTOPERATIVE MANAGEMENT: Until wound healing, soft cotton dressing should protect the vascular pedicle from pressure; immobilisation on a palmar splint may be helpful. RESULTS: In 9 men, sufficient soft tissue reconstruction of thumb defects could be achieved with the described Moschella flap. Eight patients had additional injuries to the fingers and hand.

TNF-α modulation via Etanercept restores bone regeneration of atrophic non-unions.

Treatment of atrophic non-unions, especially in long bones is a challenging problem in orthopedic surgery due to the high revision and failure rate after surgical intervention. Subsequently, there is a certain need for a supportive treatment option besides surgical treatment. In our previous study we gained first insights into the dynamic processes of atrophic non-union formation and observed a prolonged inflammatory reaction with upregulated TNF-α levels and bone resorption. In this study we aimed to improve bone regeneration of atrophic non-unions via TNF-α modulation in a previously established murine femoral segmental defect model. Animals that developed atrophic non-unions of the femur after 5 and 10 weeks were treated systemically for 10 and 5 weeks with Etanercept, a soluble TNF-α antibody. µCT scans and histology revealed bony bridging of the fracture gap in the treatment group, while bone formation in control animals without treatment was not evident. Moreover, osteoclasts were markedly decreased via modulation of the RANKL/OPG axis due to Etanercept treatment. Additionally, immunomodulatory effects via Etanercept could be observed as further inflammatory agents, such as TGF-ß, IL6, MMP9 and 13 were decreased in both treatment groups. This study is the first showing beneficial effects of Etanercept treatment on bone regeneration of atrophic non-union formation. Moreover, the results of this study provide a new and promising therapeutic option which might reduce the failure rate of revision surgeries of atrophic non-unions.

Local Wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis.

Impaired bone homeostasis caused by osteomyelitis provokes serious variations in the bone remodeling process, thereby involving multiple inflammatory cytokines to activate bone healing. We have previously established a mouse model for post-traumatic osteomyelitis and studied bone regeneration after sufficient debridement. Moreover, we could further characterize the postinfectious inflammatory state of bony defects after debridement with elevated osteoclasts and decreased bone formation despite the absence of bacteria. In this study, we investigated the positive effects of Wnt-pathway modulation on bone regeneration in our previous established mouse model. This was achieved by local application of Wnt3a, a recombinant activator of the canonical Wnt-pathway. Application of Wnt3a could enhance new bone formation, which was verified by histological and µ-CT analysis. Moreover, histology and western blots revealed enhanced osteoblastogenesis and downregulated osteoclasts in a RANKL-dependent manner. Further analysis of Wnt-pathway showed downregulation after bone infections were reconstituted by application of Wnt3a. Interestingly, Wnt-inhibitory proteins Dickkopf 1 (DKK1), sclerostin, and secreted frizzled protein 1 (sFRP1) were upregulated simultaneously to Wnt-pathway activation, indicating a negative feedback for active form of Beta-catenin. In this study, we could demonstrate enhanced bone formation in defects caused by post-traumatic osteomyelitis after Wnt3a application. KEY MESSAGES: Osteomyelitis decreases bone regeneration Wnt3a restores bone healing after infection Canonical Wnt-pathway activation with negative feedback.

Enzymatic debridement of hands with deep burns: a single center experience in the treatment of 52 hands.

Background: Bromelain-based enzymatic debridement has been introduced as an alternative to surgical excision in deep partial thickness and full thickness burns. We aimed to analyze effectiveness and predictors of spontaneous epithelialization after enzymatic debridement of deep hand burns.Methods: All patients who received enzymatic debridement for deep partial thickness or full thickness burns of the hands at our institution in the last 5 years were identified. Demographic, clinical and outcome data were collected and analyzed. For patients with deep partial thickness burns, Kaplan-Meier log-rank and subsequent multivariate Cox-regression analysis were performed to identify predictors of spontaneous epithelialization.Results: 44 patients and 52 hands were treated in the observation period. Among these, 14 had full thickness burns and received split thickness skin grafts. In the 38 hands with deep partial thickness burns, predictors of 28-day epithelialization were total burn extent and mechanism of burn injury. During the first 3 years, 8 out of 13 treated deep partial thickness burns received split thickness skin grafts after a median of 3 days. The following 3 years, 5 out of 25 deep partial thickness burns received surgery after a median of 14 days.Conclusions: Enzymatic debridement is a useful tool in the treatment of burned hands but the decision-making and correct timing of operative intervention in deep partial thickness burns after debridement requires experience. In our cohort, spontaneous healing of deep partial thickness burns was best in patients with contact burns and less than 15% burn TBSA.

Body mass index and abdominal wall thickness correlate with perforator caliber in free abdominal tissue transfer for breast reconstruction.

INTRODUCTION: The aim of the study was to investigate the relationship of BMI and abdominal wall thickness (AWT) with the diameter of the dominant deep inferior epigastric artery perforator (DIEP) as well as DIEA branching pattern in preoperatively performed computed tomography angiography (CTA). PATIENTS AND METHODS: We conducted a retrospective study including all patients undergoing DIEP flap breast reconstruction with available CTAs from November 2013 to April 2018 in our department. The caliber-strongest DIEP was detected after passage of the rectus fascia as well as the superficial inferior epigastric artery (SIEA) and correlated with the AWT 5 cm above and below the umbilicus, lateral at the level of the umbilicus and at the level of the anterior superior iliac spine (ASIS), and with BMI. RESULTS: Seventy-seven patients met the inclusion criteria (age: 47.3 ± 8.9 years). We observed a significant relationship (p < 0.05) between DIEP (mean ∅ = 2.98 mm) and BMI (r = 0.353), the AWT supra- and infraumbilical (r ≥ 0.32), and the AWT lateral at the level of the umbilicus and ASIS (r ≥ 0.25). In addition, there was a highly significant correlation (p < 0.01) between SIEA and BMI (r = 0.389) and between the AWT lateral at the level of ASIS (r ≥ 0.41). CONCLUSION: We demonstrated a correlation of the diameter of the dominant DIEP with both BMI and AWT. Focusing on the diameter, in patients with a high AWT at the level of the ASIS, the SIEA, if present, may represent an alternative therapeutic option.

Alterations in pectoralis muscle cell characteristics after radiation of the human breast in situ.

The life-time risk of being diagnosed with breast cancer is ~12%, hence breast cancer is by far the most common cancer among women. The multimodal treatment concept of breast cancer often intends radiation. The utilized ionizing radiation leads changes in the tissue resulting in tissue damage due to an alteration of molecular factors. The goal of this study was to identify the role of muscle-catabolic proteins after radiation of human pectoralis major muscles in situ. Tissue of the pectoralis major muscle was collected in 12 breast cancer patients after radiation (maximum 3 years after radiation) undergoing a deep inferior epigastric perforator free-flap breast reconstruction. At the same time, an intraindividual comparison to rectus abdominis muscle was carried out upon free-flap elevation. Immunological properties, cell proliferation, differentiation as well as the expression profile of the muscle tissue were investigated through immunohistological reactions, a DNA-microarray and histology. We found significantly increased neutrophil immigration in the radiated muscle tissue. At the same time, proteins responsible for muscular atrophy and apoptosis were significantly elevated in immunohistochemistry. A DNA microarray detected immunological upregulation and myo-differentiative disorders in radiated muscle tissue. This novel study investigating catabolism in radiated muscle in situ can serve as a basis for the treatment of radiation-accompanied muscle disorders.

Negative Impact of Wound Complications on Oncologic Outcome of Soft Tissue Sarcomas of the Chest Wall.

A link of complications with worse oncologic prognosis has been established for multiple malignancies, while the limited literature on soft-tissue sarcomas is inconclusive. The aim of this study was to examine risk factors and the oncologic impact of wound complications after curative resection of primary soft-tissue sarcomas of the chest wall. Patients with primary soft tissue sarcomas of the chest wall were identified. Groups with and without wound complications were compared by using univariate and multivariate analysis to identify risk factors. For patients with clear surgical margins (R0), univariate and multivariate analysis of factors associated with 5-year local recurrence free survival (LRFS), metastasis free survival (MFS), and disease specific survival (DSS) were performed. A total of 102 patients were included in the study. Wound complications occurred in 11 patients (10.8%) within 90 days. Cardiovascular morbidity and operation time represented independent risk factors for wound complications. In 94 patients with clear surgical margins, those with wound complications had an estimated 5-year LRFS of 30% versus 72.6% and a 5-year DSS of 58.3% versus 82.1%. Wound complications could be identified as an independent predictor for worse LRFS and DSS. Patients with a high risk of wound complications should be identified and strategies implemented to reduce surgical complications and possibly improve oncologic prognosis.

[The revenue from finger replantation and revision amputation: Is it cost-covering?] / Fingeramputationen und -replantationen bei unterschiedlichen Kostenträgern: Ist die Vergütung kostendeckend?

BACKGROUND: Finger amputation injuries are frequently treated conditions in occupational accident hospitals. They are either treated by replantation or revision amputation. The costs of these two treatment options differ significantly. This study aims to determine if the revenue generated from the treatment of finger amputation injuries in the German DRG system is cost-covering and if there are differences depending on the type of health insurance. METHODS: Based on our hospital's cost data from the years 2014 and 2015, we performed an analysis of the revenue generated from finger replantation and finger revision amputation and compared it with the cost data of the nationwide calculation hospitals in Germany. In addition, we compared the revenue generated from patients with statutory health insurance with the revenue from patients with workers' compensation insurance. RESULTS: During the study period, a total of 90 patients were treated for finger amputation. For primary finger revision amputation, the actual costs were lower compared to the cost data of the nationwide calculation hospitals (€ 3551 vs. € 3809, p = 0.442). After deduction of all costs, the revenue was 1,008 Euros for patients with statutory health insurance and 688 Euros for patients with workers' compensation insurance (p = 0.578). In contrast, the costs of complex finger reconstruction procedures were considerably underestimated. In cases of primary finger replantation or secondary finger revision amputation, losses of 260 Euros were recorded for patients with statutory health insurance. In patients with workers' compensation insurance, the revenue of complex finger reconstruction procedures after deduction of all costs was cost-covering (€ 900, p = 0.403). CONCLUSIONS: In the German DRG system, the reimbursement for the treatment of finger amputation depends on the type of health insurance. In patients with workers' compensation insurance, cost-covering revenue is generated from both finger revision amputation and finger replantation, whereas in patients with statutory health insurance, only the revenue of primary finger revision amputation appears to be cost-covering. Hence for finger amputation injuries with subsequent complex reconstruction procedures, a revision of the cost calculation is required to avoid inappropriate incentives in patient care.

Interaction of quality of life, mood and depression of patients and their informal caregivers after surgical treatment of high-grade glioma: a prospective study.

INTRODUCTION: Patients who are diagnosed with high-grade gliomas (HGG) have poor prognoses and often experience rapid declines in functional and cognitive status, which makes caring for them particularly stressful. We conducted a prospective study to investigate the factors influencing the quality of life of HGG patients and their informal caregivers and analyzed their reciprocal impacts. Based on our results, we elaborated a screening model to identify patients and caregivers in need of psychooncological support. METHODS: A total of 45 matched HGG patient-caregiver dyads completed the Multidimensional Mood State Questionnaire, the 12-Item Short Form Medical Outcome Questionnaire and the Center for Epidemiology Studies Depression Scale. A subsequent semi-structured interview was performed with each individual. RESULTS: We found a significant relationship between the mood and depression scores of patients and caregivers, with a third of them displaying symptoms of a major depressive episode. Our screening model showed that 73% of the dyads exhibited signs of severe emotional strain with the need of psychooncological support. Beneficial factors that helped patients and caregivers cope with the illness included mutual respect, good communication, caregiver mastery and resilience. CONCLUSIONS: For a more comprehensive understanding of patient-caregiver interactions, we recommend using a combination of standardized psychometric tests and a semi-structured interview. The high percentage of emotional strain and depression found in patients and their caregivers facing HGG highlights the necessity of methodical screening for warning signs and consequent initiation of psycho-oncological interventions.