Continuous NPWT regulates fibrosis in murine diabetic wound healing

Scarring is associated with significant morbidity. The mechanical signaling factor yes-associated protein (YAP) has been linked to Engrailed-1 (En1)-lineage positive fibroblasts (EPFs), a pro-scarring fibroblast lineage, establishing a connection between mechanotransduction and fibrosis. In this study, we investigate the impact of micromechanical forces exerted through negative pressure wound therapy (NPWT) on the pathophysiology of fibrosis. Full-thickness excisional dorsal skin wounds were created on diabetic (db/db) mice which were treated with occlusive covering (control) or NPWT (continuous, -125 mmHg, 7 days; NPWT). Analysis was performed on tissue harvested 10 days after wounding. NPWT was associated with increased YAP

Identification of a Phage Display-Derived Peptide Interacting with the N-Terminal Region of Factor VII Activating Protease (FSAP) Enables Characterization of Zymogen Activation

publishedVersio

Association of age with perioperative morbidity among patients undergoing surgical management of minor burns

Introduction: Burn injuries are associated with significant morbidity, often necessitating surgical management. Older patients are more prone to burns and more vulnerable to complications following major burns. While the relationship between senescence and major burns has already been thoroughly investigated, the role of age in minor burns remains unclear. To better understand differences between elderly and younger patients with predominantly minor burns, we analyzed a multi-institutional database. Methods: We reviewed the 2008-2020 ACS-NSQIP database to identify patients who had suffered burns according to ICD coding and underwent initial burn surgery. Results: We found 460 patients, of which 283 (62%) were male and 177 (38%) were female. The mean age of the study cohort was 46 ± 17 years, with nearly one-fourth (n = 108; 23%) of all patients being aged ≥60 years. While the majority (n = 293; 64%) suffered from third-degree burns, 22% (n = 99) and 15% (n = 68) were diagnosed with second-degree burns and unspecified burns, respectively. An average operation time of 46 min, a low mortality rate of 0.2% (n = 1), a short mean length of hospital stay (1 day), and an equal distribution of in- and outpatient care (51%, n = 234 and 49%, n = 226, respectively) indicated that the vast majority of patients suffered from minor burns. Patients aged ≥60 years showed a significantly prolonged length of hospital stay (p0.0001), creatinine (p>0.0001), white blood cell count (p=0.02), partial thromboplastin time (p = 0.004), and lower levels of albumin (p = 0.0009) and hematocrit (p>0.0001) were identified as risk factors for the occurrence of any complication. Further, complications were more frequent among patients with lower body burns. Discussion: In conclusion, patients ≥60 years undergoing surgery for predominantly minor burns experienced significantly more complications. Minor lower body burns correlated with worse outcomes and a higher incidence of adverse events. Decreased levels of serum albumin and hematocrit and elevated values of blood urea nitrogen, creatinine, white blood count, and partial thromboplastin time were identified as predictive risk factors for complications

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Donor Site Morbidity in Unilateral and Bilateral Transverse Musculocutaneous Gracilis (TMG) Flap Breast Reconstruction: Sensation, Function, Aesthesis and Patient-Reported Outcomes

The transverse musculocutaneous gracilis (TMG) flap has become a popular choice for breast reconstruction. This study aimed to compare the donor site morbidity in unilateral and bilateral procedures. Patients receiving a TMG flap (January 2008–October 2019) were invited to a follow-up and grouped according to unilateral (UL group) or bilateral (BL group) breast reconstruction. Outcome criteria included sensation, function and aesthesis of the thighs. Patient-reported outcomes were surveyed using validated questionnaires. The number and kind of refinement procedures for aesthetic purposes on the donor thighs were evaluated. Thirty-eight patients with 59 TMG flaps were included in the study (UL group: n = 17, BL group: n = 21). Normal to slightly diminished superficial skin sensation was maintained in most of the thigh skin (98.4%). Strength and mobility were without impairment in >80% of the thighs in both groups. Thigh symmetry was achieved in both groups. Symmetrisation procedures were significantly more often performed in the UL group (p = 0.005). The total number of refinement procedures was similar in both groups. Patient-reported outcomes were similar with good appearance of the thighs and scars, excellent function and low pain levels. The TMG flap offers excellent function and sensation on the donor thigh. Thigh symmetry and good patient satisfaction may be achieved in both unilateral and bilateral breast reconstructions

Effective or Harmful—Evaluation of Locally Applied Antibiotics on Adipose Tissue during Lipofilling to the Breast—An In Vitro Study

Lipofilling is a frequently used and safe procedure for breast reconstruction. One of the most feared complications is soft tissue infection following lipofilling. Because of this, some surgeons propose the practice of rinsing fat grafts with antibiotics. This study investigates the effect of antibiotic rinses on fat grafts in an in vitro model. Adipocytes and stem cells were isolated from fat tissue harvested during 24 lipofilling procedures and incubated with different doses of clindamycin or cefazolin. Cell viability, metabolism, proliferation, and differentiation capacities were analyzed by gross morphology, fluorescence staining, -(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT-), and Glyceraldehyde 3 Phosphate Dehydrogenase (G3PD)-assay as well as reactive oxygen species (ROS)-assay. Cefazolin and clindamycin led to significant reduction of cell viability of adipocytes. High doses of both antibiotics led to a rupture of adipocytes with visible free lipid droplets. Cell metabolism was significantly decreased after incubation with both antibiotics. There was a significant increase in ROS production. Exposure to clindamycin and cefazolin led to morphological changes in stem cells in a dose- and time-dependent manner. Furthermore, differentiation potential was significantly reduced. Antibiotic susceptibility testing, however, showed that low concentrations of antibiotics effectively inhibited bacterial growth in contaminated fat grafts. This study confirms that rinsing fat grafts with clindamycin or cefazolin not only overly prevents infection but also has cytotoxic and metabolic effects on adipocytes. Therefore, based on these results, the routine clinical application in high doses cannot be recommended

Oral doxycycline prevents skin-associated adverse effects induced by injectable collagenase in a rodent model of capsular contracture around silicone implants.

BackgroundThe collagenase of the bacterium Clostridium histolyticum (CCH) is already an established treatment for fibroproliferative diseases like M. Dupuytren and M. Peyronie Although results are comparable to surgical intervention, skin laceration is a severe and relevant side effect. Doxycycline (DOX) recently rose interest as an inhibitor of matrix-metalloproteinases alongside its capabilities of skin accumulation. It therefore might be a potential skin protective agent in the use of CCH.MethodsFor simulation of a fibroproliferative disease adjacent to the skin, we utilized a rodent model of capsular fibrosis involving silicone implants and subsequent fibrotic capsule formation. For in-vitro studies, fibrotic capsules were excised and incubated with 0.9 mg/ml CCH and four different doses of DOX. For in-vivo experiments, animals received 0.0, 0.3 or 0.9 mg/ml CCH injections into the fibrotic capsules with or without prior oral DOX administration. Outcome analysis included histology, immunohistochemistry, gene expression analysis, chemical collagen and DOX concentration measurements as well as μCT imaging.ResultsIn-vitro, DOX showed a dose-dependent inhibition of CCH activity associated with increasing capsule thickness and collagen density and content. In-vivo, oral DOX administration did neither interfere with capsule formation nor in effectiveness of CCH dissolving fibrotic capsule tissue. However, skin thickness and especially collagen density was significantly higher compared to control groups. This led to a reduced rate of clinical skin lacerations after DOX administration.ConclusionDOX inhibits CCH and accumulates in the skin. Thereby, DOX can effectively reduce skin laceration after CCH treatment

The Use of Closed Incision Negative Pressure Therapy on the Medial Thigh Donor Site in Transverse Musculocutaneous Gracilis Flap Breast Reconstruction

The objective of this study was to examine the impact of closed incision negative pressure therapy (CINPT) on donor site complications and patient perceptions in transverse musculocutaneous gracilis (TMG) flap breast reconstruction. Our institution conducted a retrospective cohort study, including all patients with TMG flap breast reconstruction from 1 January 2010 to 31 December 2021. Patients were grouped according to conventional wound management or CINPT. Outcomes were surgical site complications, fluid drainage, time to drain removal, and in-hospital stay length. A patient survey was created. A total of 56 patients with 83 TMG flaps were included (control group: 35 patients with 53 TMG flaps; CINPT group: 21 patients with 30 TMG flaps). Patient characteristics were similar in both groups. The flap width was significantly larger in the CINPT group (8.0 cm vs. 7.0 cm, p = 0.013). Surgical site complications were reduced in the CINPT group without statistical difference (30.0% vs. 50.9%, p = 0.064). Fluid drainage and time to drain removal were similar in both groups. The average in-hospital stay was significantly shortened in the CINPT group (10.0 days vs. 13.0 days, p = 0.030). The survey excluded pain, skin irritations, and discomfort during sleep and movement in the CINPT group and showed that the patients felt well protected. This study fails to provide compelling evidence for CINPT to enhance incision healing on the donor site in TMG flap breast reconstruction. There was a trend toward reduced surgical site complications on the donor thigh and the in-hospital stay was shortened. Prophylactic CINPT increases patient comfort and provides a feeling of additional wound protection