Superior enhancement of cutaneous microcirculation due to "cyclic" application of a negative pressure wound therapy device in humans

$\bf Objectives:$ Despite a common utilization of "Negative Pressure Wound Therapy" (NPWT) Devices in a wide range of specialties, some of the basic mechanisms of action of the techniques are still on debate. Conflicting results from prior studies demonstrate our lack of understanding how wound-bed perfusion or cutaneous microcirculation is affected by NPWT. $\bf Methods:$ We conducted a prospective randomized study which included 45 healthy subjects to further investigate the acute effects of NPWT on cutaneous microcirculation underneath the applied dressing. Three modes of application, namely, continuous, intermittent, cyclic, were tested. Amongst others, measurements of elicited surface pressure and a comprehensive microcirculatory analysis were carried out by utilizing an O2C-device. For the detection of (systemic) remote effects, perfusion changes of the contra-lateral thigh were evaluated. $\bf Results:$ All three tested modes of application led to a significant ($\it p$ < 0.05) improvement in local tissue perfusion with an increased blood flow of max +151% and tissue oxygen saturation of +28.2% compared to baseline values. Surface pressure under the dressing significantly increased up to 29.29 mmHg due to the activation of the NPWT device. Continuous, intermittent, and cyclic application of negative pressure were accurately sensed by participants, resulting in reported pain values that mirrored the different levels of applied suction. Although the cyclic application mode showed the most pronounced effects regarding microcirculatory changes, no statistical significance between groups was observed. $\bf Conclusion:$ We could demonstrate a significant improvement of cutaneous microcirculation under an applied NPWT dressing with favorable effects due to cyclic mode of application. An increased surface pressure leads to a better venous drainage of the tissue, which was shown to increase arterial inflow with a consecutive improvement of oxygen supply. Further research is warranted to evaluate our findings regarding wound bed perfusion in the clinical field with respect to formation of granulation tissue and wound healing

Autologous vs. implant-based breast reconstruction after skin- and nipple-sparing mastectomy

$\bf Introduction:$ Autologous (ABR) and implant-based breast reconstruction (IBR) represent the most common procedures after skin- and nipple-sparing mastectomy. This cross-sectional study is a comprehensive analysis of ABR and IBR considering surgical and patient-reported outcomes. $\textbf {Patients and methods:}$ Eligible patients underwent breast reconstruction (ABR and IBR) after skin- and nipple-sparing mastectomy between January 2014 and December 2020. Outcome parameters included quality of life (European Organisation for Research and Treatment of Cancer - EORTC - QLQ30, BR23, Breast-Q, CES-D), complication rates, aesthetic result, and breast sensitivity. $\bf Results:$ 108 patients participated in the study (IBR: $\it n$ = 72, age 48.9 $\pm$ 9.9 years; ABR: $\it n$ = 36, age: 46.6 $\pm$ 7.3 years). Mean follow-up was 27.1 $\pm$ 9.3 (IBR) and 34.9 $\pm$ 20.5 (ABR), respectively. IBR patients suffered significantly more often from major complications (30.6% vs. 8.3%; $\it p$ = 0.01), while ABR patients underwent secondary procedures significantly more often to improve the aesthetic result (55.6% vs. 29.2%, $\it p$ = 0.004). Unilateral reconstructions revealed superior aesthetic results in ABR (n.s.), while in bilateral reconstruction IBR tended to score higher (n.s.). Scar evaluation resulted in a better result of IBR in both categories ($\it p$ < 0.01). Breast sensitivity was severely impaired in both groups. The Breast-Q revealed a significantly higher "patient satisfaction with breast" after ABR ($\it p$ = 0.033), while the other QoL-tests and subscales showed no significant differences between the two procedures. $\bf Conclusion:$ ABR is associated with a higher patient satisfaction despite the high probability of secondary procedures to improve the aesthetic outcome, whereas IBR-patients suffer more often from major complications. Furthermore, the laterality of reconstruction should be included in the individual decision-making process

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 impact of surgical margins and adjuvant radiotherapy in patients with undifferentiated pleomorphic sarcomas of the extremities

$\textit {Background:}$ Undifferentiated pleomorphic sarcomas are a frequent subtype within the heterogeneous group of soft tissue sarcomas. As the attainment of negative margins can be complicated at the extremities, we determined the prognostic significance of surgical margins in our patient population. $\textit {Methods:}$ We retrospectively determined the relationship between local recurrence-free survival (LRFS), overall survival (OS), and potential prognostic factors in 192 patients with UPS of the extremities who were suitable for surgical treatment in curative intent. The median follow-up time was 5.1 years. $\textit {Results:}$ The rates of LRFS and OS after 2 years were 75.7% and 87.2% in patients with R0-resected primary tumors and 49.1% and 81.8% in patients with R1/R2-status (LRFS: $\it p$ = 0.013; OS: $\it p$ = 0.001). Adjuvant radiotherapy significantly improved LRFS (5-year: 67.6% vs. 48.4%; $\it p$ < 0.001) and OS (5-year: 82.8 vs. 61.8; $\it p$ = 0.016). Both, negative margins and adjuvant radiotherapy were found to be independent prognostic factors in multivariate analysis. $\textit {Conclusions:}$ The data from this study could underscore the beneficial prognostic impact of negative margins on LRFS and OS. However, the width of negative margins seemed to be not relevant. Notably, adjuvant radiotherapy was not only able to decrease the risk of local failure but also improved OS in a significant manner

Antibiotic prophylaxis for prevention of wound infections after soft tissue sarcoma resection

Background and Objectives The use of antibiotic prophylaxis for soft tissue sarcoma resection varies widely while little evidence on this topic exists. The aim of this study was to determine the impact of antibiotic prophylaxis on the occurrence of wound infections. Methods A single institutional retrospective cohort study was performed on patients who underwent truncal or extremity soft tissue sarcoma resection. The use of antibiotic prophylaxis was assessed and univariate and multivariate analysis of predictors of wound infections was performed. Results Nine hundred and fifty-eight patients could be included. Thirty-two percent of patients had no antibiotic prophylaxis, 44% of patients received single-shot prophylaxis, and 24% of patients received single-shot plus continued antibiotic treatment. Wound infections occurred in 140 patients (15%). Independent risk factors for wound infections upon multivariate analysis were obesity, high American Society of Anesthesiologists (ASA) status, high tumor size and grade, operation time over 120 minutes, and other complications. Antibiotic prophylaxis could not be identified as a protective factor in univariate or multivariate analysis. Conclusions A favorable effect of antibiotic prophylaxis on the occurrence of wound infections could not be observed. Although more studies on this subject are needed, our data do not support the general use of antibiotic prophylaxis for soft tissue sarcoma resection

Inhibition of GDF8 (Myostatin) accelerates bone regeneration in diabetes mellitus type 2

Metabolic diseases like diabetes mellitus cause bone healing deficiencies. We found significant impairment of bone regeneration, osteogenic differentiation and proliferation in diabetic bone. Moreover recent studies suggest a highly underestimated importance of GDF8 (Myostatin) in bone metabolism. Our goal was to analyze the role of GDF8 as a regulator of osteogenic differentiation, proliferation and bone regeneration. We used a murine tibial defect model in diabetic ($Lepr^{db-/-}$) mice. Myostatin-Inhibitor Follistatin was administered in tibial bony defects of diabetic mice. By means of histology, immunohistochemistry and QRT-PC osteogenesis, differentiation and proliferation were analyzed. Application of Myostatin-inhibitor showed a significant improvement in diabetic bone regeneration compared to the control group (6.5 fold, p < 0.001). Immunohistochemistry revealed a significantly higher proliferation (7.7 fold, p = 0.009), osteogenic differentiation (Runx-2: 3.7 fold, p = 0.011, ALP: 9.3 fold, p < 0.001) and calcification (4.9 fold, p = 0.024) in Follistatin treated diabetic animals. Therapeutical application of Follistatin, known for the importance in muscle diseases, plays an important role in bone metabolism. Diabetic bone revealed an overexpression of the catabolic protein Myostatin. Antagonization of Myostatin in diabetic animals leads to a restoration of the impaired bone regeneration and represents a promising therapeutic option

Maggot extract interrupts bacterial biofilm formation and maturation in combination with antibiotics by reducing the expression of virulence genes

Biofilms are aggregates of bacteria encased in an extracellular polymer matrix that acts as a diffusion barrier protecting the microbial community. Bacterial communication occurs by small signaling molecules called quorum sensing (QS) factors, which are involved in the activation of virulence genes and formation of biofilms. Larvae of the green bottle blowfly $\textit {Lucilia sericata}$ remove necrotic tissue by mechanical action (debridement) and proteolytic digestion. We produced a freeze-dried storable powder from larval extract and investigated its therapeutic effect on biofilms. Larval extract in concentrations of 6 and 12 mg/mL in combination with 0.5% antibiotics (≙50 U/mL penicillin and 50 $\mu$g/mL streptomycin) diminished free-floating (planktonic) $\textit {Pseudomonas aeruginosa}$ maintenance, while it showed no effect on $\textit {Staphylococcus aureus}$ and was not toxic to dermal cells. We established an ex vivo human dermal wound model. Larval extract in concentrations of 24 and 75 mg/mL in the presence of antibiotics (0.5%) significantly destroyed the biofilm stability of both $\textit {P. aeruginosa}$ and $\textit {S. aureus}$ biofilms. Furthermore, SEM analyses revealed crack and gap formations on $\textit {P. aeruginosa}$. biofilm surface and decreased expression of $\textit {P. aeruginosa}$ biofilm maturation and virulence genes ($\it lasR$, $\it rhlR$ and $\it rhlA$) was observed after treatment by larval extract in combination with antibiotics