Lymphatic malformations (LM) are characterized by the overgrowth of lymphatic vessels during pre- and postnatal development. Macrocystic, microcystic and combined forms of LM are known. The cysts are ...lined by lymphatic endothelial cells (LECs). Resection and sclerotherapy are the most common treatment methods. Recent studies performed on LM specimens in the United States of America have identified activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene in LM. However, whole tissue but not isolated cell types were studied. Here, we studied LM tissues resected at the University Hospitals Freiburg and Regensburg, Germany. We isolated LECs and fibroblasts separately, and sequenced the commonly affected exons 8, 10, and 21 of the PIK3CA gene. We confirm typical monoallelic mutations in 4 out of 6 LM-derived LEC lines, and describe two new mutations i.) in exon 10 (c.1636C>A; p.Gln546Lys), and ii.) a 3bp in-frame deletion of GAA (Glu109del). LM-derived fibroblasts did not possess such mutations, showing cell-type specificity of the gene defect. High activity of the PIK3CA-AKT- mTOR pathway was demonstrated by hyperphosphorylation of AKT-Ser473 in all LM-derived LECs (including the ones with newly identified mutations), as compared to normal LECs. Additionally, hyperphosphorylation of ERK was seen in all LM-derived LECs, except for the one with Glu109del. In vitro, the small molecule kinase inhibitors Buparlisib/BKM-120, Wortmannin, and Ly294002, (all inhibitors of PIK3CA), CAL-101 (inhibitor of PIK3CD), MK-2206 (AKT inhibitor), Sorafenib (multiple kinases inhibitor), and rapamycin (mTOR inhibitor) significantly blocked proliferation of LM-derived LECs in a concentration-dependent manner, but also blocked proliferation of normal LECs. However, MK-2206 appeared to be more specific for mutated LECs, except in case of Glu109 deletion. In sum, children that are, or will be, treated with kinase inhibitors must be monitored closely.
Lipofilling is an option for breast reconstruction after tumor resection to avoid the complications of an implant-based reconstruction. Although some concerns exist regarding the oncological safety ...of tissue rich in mesenchymal stem cells with their proangiogenic and proliferation-supportive properties, there are also reports that adipose-tissue-derived stem cells can exhibit antitumoral properties. We isolated primary adipose-tissue-derived stem cells. Both conditioned medium and exosomes were harvested from the cell culture and used to treat the breast cancer cell line MCF-7. Cell viability, cytotoxicity, and gene expression of MCF-7 cells in response to the indirect co-culture were evaluated. MCF-7 cells incubated with exosomes from adipose-tissue-derived stem cells show reduced cell viability in comparison to MCF-7 cells incubated with adipose-tissue-derived stem-cell-conditioned medium. Expression of proapoptotic genes was upregulated, and expression of antiapoptotic genes was downregulated. The debate about the oncological safety of autologous fat grafting after tumor resection continues. Here, we show that exosomes from adipose-tissue-derived stem cells exhibit some antitumoral properties on breast cancer cell line MCF-7.
Wound healing in the 21st century Schreml, Stephan, MD; Szeimies, Rolf-Markus, MD, PhD; Prantl, Lukas, MD, PhD ...
Journal of the American Academy of Dermatology,
11/2010, Letnik:
63, Številka:
5
Journal Article
Recenzirano
Delayed wound healing is one of the major therapeutic and economic issues in medicine today. Cutaneous wound healing is an extremely well-regulated and complex process basically divided into 3 ...phases: inflammation, proliferation, and tissue remodeling. Unfortunately, we still do not understand this process precisely enough to give direction effectively to impaired healing processes. There have been many new developments in wound healing that provide fascinating insights and may improve our ability to manage clinical problems. Our goal is to acquaint the reader with selected major novel findings about cutaneous wound healing that have been published since the beginning of the new millennium. We discuss advances in areas such as genetics, proteases, cytokines, chemokines, and regulatory peptides, as well as therapeutic strategies, all set in the framework of the different phases of wound healing.
Lagophthalmos is the incomplete closure of the eyelids posing the risk of corneal ulceration and blindness. Lagophthalmos is a common symptom of various pathologies. We aimed to program a ...convolutional neural network to automatize lagophthalmos diagnosis. From June 2019 to May 2021, prospective data acquisition was performed on 30 patients seen at the Department of Plastic, Hand, and Reconstructive Surgery at the University Hospital Regensburg, Germany (IRB reference number: 20-2081-101). In addition, comparative data were gathered from 10 healthy patients as the control group. The training set comprised 826 images, while the validation and testing sets consisted of 91 patient images each. Validation accuracy was 97.8% over the span of 64 epochs. The model was trained for 17.3 min. For training and validation, an average loss of 0.304 and 0.358 and a final loss of 0.276 and 0.157 were noted. The testing accuracy was observed to be 93.41% with a loss of 0.221. This study proposes a novel application for rapid and reliable lagophthalmos diagnosis. Our CNN-based approach combines effective anti-overfitting strategies, short training times, and high accuracy levels. Ultimately, this tool carries high translational potential to facilitate the physician's workflow and improve overall lagophthalmos patient care.
Background
Dogmatic denial of vasopressor agents for blood pressure regulation during free-flap surgery is associated with concomitant large-volume intraoperative fluid administration. Yet, the ...doctrinal banning of vasopressors during microvascular breast reconstruction still is a subject of controversy. Several retrospective observations have recently drawn attention to serious iatrogenic consequences of intravenous crystalloid overload in microsurgery such as thrombus formation and increased flap failure rates.
Methods
This prospective randomized controlled trial investigated the potential effects of fluid-restrictive vasopressor-dominated hemodynamic support (FRV) compared with vasopressor-restrictive liberal fluid administration (LFA) on clinically relevant perfusion of the deep inferior epigastric perforator (DIEP) flap via intraoperative indocyanine green (ICG) fluorescence imaging. The primary end point of the study was quantitative assessment of the percentage of insufficiently perfused tissue (NP) on the overall flap. Major complications were assessed as secondary end points.
Results
In 44 DIEP flap breast reconstructions after mastectomy, FRV circulatory support resulted in no statistically significant difference in total flap perfusion as detected via ICG fluorescence imaging in direct comparison with a traditional LFA strategy (NP
FRV
, 31.8% ± 12.2% vs NP
LFA
, 29.5% ± 13.3%;
p
= 0.559). One flap failure was registered with LFA, whereas no major complication occurred in the FRV cohort.
Conclusions
According to the results of this study, neither a norepinephrine concentration of 0.065 ± 0.020 μg/kg/min (FRV) nor fluid administration of 5.1 ± 2.2 ml/kg/h (LFA) has a clinically significant impact on microperfusion in a standard DIEP flap procedure for breast reconstruction. Consistent with the current literature reporting a rise in complications with intraoperative fluid over-resuscitation, one flap failure occurred in the LFA cohort.
ZusammenfassungFrakturassoziierte Infektionen sind gefürchtete Komplikationen nach operativer Frakturversorgung. Vor allem der distale Unterschenkel ist (z. B. bei Pilon-tibiale-Frakturen) aufgrund ...der schlechten Weichteildeckung einem hohen Infektionsrisiko ausgesetzt. Im besonderen Maße gilt dies v. a. für offene Frakturen in diesem Bereich. Frakturassoziierte Infektionen mit bedeutsamen Weichteilschaden bedürfen, neben der Behandlung der frakturassoziierten Infektion selbst, einer besonderen Aufmerksamkeit aufgrund des Weichteildefekts. Generell gilt das Prinzip, dass ohne eine suffiziente Weichteildeckung eine Ausheilung der frakturassoziierten Infektion nicht möglich ist. Daher gilt es, sowohl den Weichteilschaden als auch die frakturassoziierte Infektion von Anfang an in ein schlüssiges Behandlungskonzept zu bringen. Hierzu ist oftmals eine Kooperation zwischen Unfallchirurgie und Plastischer Chirurgie notwendig und sinnvoll. In Fällen, bei denen das Osteosynthesematerial bzw. Knochen freiliegen, ist die mittel- oder gar langfristige Anwendung von vakuumassistierter Wundtherapie nicht sinnvoll, da diese mit einem höheren Reinfektionsrisiko verbunden ist. Daher sollte in einer interdisziplinären Behandlungsstrategie aus Unfallchirurgie mit Plastischer Chirurgie ein frühzeitiger Weichteilverschluss („ortho-plastic approach“) angestrebt und durchgeführt werden. Sollte dies in der eigenen Klinik nicht möglich sein, so ist eine frühzeitige Verlegung des betroffenen Patienten indiziert, um eine optimale interdisziplinäre Therapie mit zeitnahem Weichteilverschluss und gleichzeitiger unfallchirurgischer Therapie zur Kontrolle der Infektion und knöcherner Ausheilung zu gewährleisten. Freie fasziokutane oder Muskellappenplastiken in Kombination mit adäquater unfallchirurgischer und antibiotischer Therapie führen zu guten und verlässlichen Ergebnissen in diesen Situationen.
Skin injury is a common occurrence and mechanical forces are known to significantly impact the biological processes of skin regeneration and wound healing. Immediately following the disruption of the ...skin, the process of wound healing begins, bringing together numerous cell types to collaborate in several sequential phases. These cells produce a multitude of molecules and initiate multiple signaling pathways that are associated with skin disorders and abnormal wound healing, including hypertrophic scars, keloids, and chronic wounds. Studies have shown that mechanical forces can alter the microenvironment of a healing wound, causing changes in cellular function, motility, and signaling. A better understanding of the mechanobiology of cells in the skin is essential in the development of efficacious therapeutics to reduce skin disorders, normalize abnormal wound healing, and minimize scar formation.
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