Hydrokolloid bei diabetischen Fussulzera: besser als herkömmliche Wundverbände

Sie betreuen einen 82-jährigen Typ-2-Diabetiker mit einer 1 cm grossen Wunde an der Grosszehe. Der Patient hat sich geschnitten, als er Hornhaut entfernte. Die Wunde vergrössert sich seither stetig und sondert Flüssigkeit ab. Die Wundumgebung ist hyperkeratotisch, aufgeweicht, leicht fibrinös und feucht. Weder ist Kontakt zum darunterliegenden Knochen vorhanden noch gibt es Infektionszeichen. Der Patient ist für eine Neuropathie und Veneninsuffizienz bekannt; die Fusspulse sind spürbar. Seine Blutzuckerwerte sind stabil, der HbA1c-Wert liegt bei 7,5%. Er möchte die Wunde selbst weiter versorgen und sich regelmässig duschen können.

Escarres et dénutrition: dépistage et évaluation de l'état nutritionnel [Pressure ulcers and undernutrition: screening and assessment of nutritional status]

Acquired pressure ulcer is associated with significant human, economic and functional consequences. Its prevalence varies between 3 and 23% in a community hospital and between 7 and 54% in an elderly home residency. Pressure ulcer healing is a complex process which involves numerous cellular and molecular mechanisms. An altered nutritional status is a contributing factor in the development of pressure ulcers and the delay in pressure ulcer healing. The key to management of undernutrition is screening and early intervention. According to the gravity of undernutrition, various degrees of intervention will be required. Systematic oral supplementation with various nutrients may provide benefit in the prevention of pressure ulcers, but further studies have to be completed in human subjects prior to being recommended for the treatment of pressure ulcers.

The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1.

The altered expression of the SOX2 transcription factor is associated with oncogenic or tumor suppressor functions in human cancers. This factor regulates the migration and invasion of different cancer cells. In this study we investigated the effect of constitutive SOX2 overexpression on the migration and adhesion capacity of embryonal teratocarcinoma NT2/D1 cells derived from a metastasis of a human testicular germ cell tumor. We detected that increased SOX2 expression changed the speed, mode and path of cell migration, but not the adhesion ability of NT2/D1 cells. Additionally, we demonstrated that SOX2 overexpression increased the expression of the tumor suppressor protein p53 and the HDM2 oncogene. Our results contribute to the better understanding of the effect of SOX2 on the behavior of tumor cells originating from a human testicular germ cell tumor. Considering that NT2/D1 cells resemble cancer stem cells in many features, our results could contribute to the elucidation of the role of SOX2 in cancer stem cells behavior and the process of metastasis.

Fibrin sealant for fasciocutaneous flaps.

Fibrin sealant is used in many areas of surgery. We present a novel aspect of flap insetting in the ischial region using fibrin spray to seal the transferred tissue. We analyzed 10 patients suffering from decubital ulcers and assessed drainage output, time of drain removal, as well as complications following fasciocutaneous flap surgery. Patients were randomized to receive sprayed fibrin glue (study group) or not (control group) before wound closure. The mean drainage time was 4 +/- 1 days in the study group and 6 +/- 1 days in the control group ( P = 0.06). The mean drainage volume was 100 +/- 20 mL in the study group and 168 +/- 30 mL in the control group ( P < 0.01). Fibrin sealant led to reduced drainage volumes and duration of drainage, indicating a beneficial effect of the application of fibrin glue in fasciocutaneous flap surgery for pressure sore coverage.

Percutaneous retrograde screwing for stabilisation of acetabular fractures.

OBJECTIVES: To evaluate the results of retrograde percutaneous screw fixation (PSF) in minimally or undisplaced acetabular fractures in a geriatric population. PATIENTS AND METHODS: Between July 1998 and July 2001, 21 consecutive patients with an acetabular fracture underwent fluoroscopic guided percutaneous fixation. The mean age was 81 years (range 67--90 years). In all cases, the fracture was minimally or undisplaced (<2mm). Two cannulated cancellous 7.3mm screws were inserted in a retrograde fashion to stabilise the posterior and the anterior column. Bed to chair transfer began after 24h. Weight bearing as tolerated was allowed at 4 weeks. RESULTS: Eighteen patients were reviewed at a mean of 3.5 years (range 2--5 years). Soft tissue dissection was minimal. There were no intraoperative or postoperative complications. At the latest follow-up there was no radiographical evidence of secondary displacement of fragments, degenerative changes, or screw failure. Fractures healed at a mean time of 12 weeks (range 8--15 weeks). Clinical results were satisfactory in 17 patients. CONCLUSION: Our results show that percutaneous screw fixation under fluoroscopic control is a safe technique to treat some pattern of acetabular fracture.

The epithelial sodium channel mediates the directionality of galvanotaxis in human keratinocytes.

Cellular directional migration in an electric field (galvanotaxis) is one of the mechanisms guiding cell movement in embryogenesis and in skin epidermal repair. The epithelial sodium channel (ENaC), in addition to its function of regulating sodium transport in kidney, has recently been found to modulate cell locomotory speed. Here we tested whether ENaC has an additional function of mediating the directional migration of galvanotaxis in keratinocytes. Genetic depletion of ENaC completely blocks only galvanotaxis and does not decrease migration speed. Overexpression of ENaC is sufficient to drive galvanotaxis in otherwise unresponsive cells. Pharmacologic blockade or maintenance of the open state of ENaC also decreases or increases, respectively, galvanotaxis, suggesting that the channel open state is responsible for the response. Stable lamellipodial extensions formed at the cathodal sides of wild-type cells at the start of galvanotaxis; these were absent in the ENaC knockout keratinocytes, suggesting that ENaC mediates galvanotaxis by generating stable lamellipodia that steer cell migration. We provide evidence that ENaC is required for directional migration of keratinocytes in an electric field, supporting a role for ENaC in skin wound healing.

Neurocutaneous sural flap in paraplegic patients.

Neurocutaneous flaps have been demonstrated to be a reliable option in different groups of patients but it remains unclear if distally-based sural flaps can be safely used in paraplegic patients because they suffer from significant nervous system alterations. The aim of this proof-of-concept study is to demonstrate that these flaps are reliable in paraplegic patients. We prospectively analysed a group (n=6) of paraplegic patients who underwent reversed sural flap surgery for ulcers on the lateral malleolus. Measurement of area and photographic documentation techniques have been employed to quantify the defect area. Sural nerve biopsies have been analysed histologically with several different staining techniques to assess the neurovascular network and the myelinisation of the nerve. The patients showed uneventful wound healing, except one case that suffered a partial flap necrosis that healed by secondary intention. Histologic analysis revealed an intact neurovascular network and myelinated nerve fibres. In this small series of paraplegic patients that underwent a distally-based sural flap, the complication rate was low, with only one case of superficial partial necrosis demonstrating the reliability and safety of the flap in this subset of patients. Histologic evaluation of sural nerve biopsies revealed an almost normal morphology. A possible explanation of this phenomenon is that the dorsal root ganglia remain intact in paraplegic patients and can preserve neural characteristics in the peripheral sensory nerve system.

The nuclear hormone receptor peroxisome proliferator-activated receptor beta/delta potentiates cell chemotactism, polarization, and migration.

After an injury, keratinocytes acquire the plasticity necessary for the reepithelialization of the wound. Here, we identify a novel pathway by which a nuclear hormone receptor, until now better known for its metabolic functions, potentiates cell migration. We show that peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) enhances two phosphatidylinositol 3-kinase-dependent pathways, namely, the Akt and the Rho-GTPase pathways. This PPARbeta/delta activity amplifies the response of keratinocytes to a chemotactic signal, promotes integrin recycling and remodeling of the actin cytoskeleton, and thereby favors cell migration. Using three-dimensional wound reconstructions, we demonstrate that these defects have a strong impact on in vivo skin healing, since PPARbeta/delta-/- mice show an unexpected and rare epithelialization phenotype. Our findings demonstrate that nuclear hormone receptors not only regulate intercellular communication at the organism level but also participate in cell responses to a chemotactic signal. The implications of our findings may be far-reaching, considering that the mechanisms described here are important in many physiological and pathological situations.

Loss of serum response factor in keratinocytes results in hyperproliferative skin disease in mice.

The transcription factor serum response factor (SRF) plays a crucial role in the development of several organs. However, its role in the skin has not been explored. Here, we show that keratinocytes in normal human and mouse skin expressed high levels of SRF but that SRF expression was strongly downregulated in the hyperproliferative epidermis of wounded and psoriatic skin. Keratinocyte-specific deletion within the mouse SRF locus during embryonic development caused edema and skin blistering, and all animals died in utero. Postnatal loss of mouse SRF in keratinocytes resulted in the development of psoriasis-like skin lesions. These lesions were characterized by inflammation, hyperproliferation, and abnormal differentiation of keratinocytes as well as by disruption of the actin cytoskeleton. Ultrastructural analysis revealed markedly reduced cell-cell and cell-matrix contacts and loss of cell compaction in all epidermal layers. siRNA-mediated knockdown of SRF in primary human keratinocytes revealed that the cytoskeletal abnormalities and adhesion defects were a direct consequence of the loss of SRF. In contrast, the hyperproliferation observed in vivo was an indirect effect that was most likely a consequence of the inflammation. These results reveal that loss of SRF disrupts epidermal homeostasis and strongly suggest its involvement in the pathogenesis of hyperproliferative skin diseases, including psoriasis.

Supraclavicular flap in head and neck reconstruction: experience in 50 consecutive patients.

The supraclavicular flap (SCF) is a fasciocutaneous flap used to cover head, oral, and neck region defects after tumor resection. Its main vascular supply is the supraclavicular artery and accompanying veins and it can be harvested as a vascularised pedicled flap. The SCF serves as an excellent outer skin cover as well as a good inner mucosal lining after oral cavity and head-neck tumor resections. The flap has a wide arc of rotation and matches the skin colour and texture of the face and neck. Between March 2006 and March 2011, the pedicled supraclavicular flap was used for reconstruction in 50 consecutive patients after head and neck tumor resections and certain benign conditions in a tertiary university hospital setting. The flaps were tunnelized under the neck skin to cover the external cervicofacial defects or passed medial to the mandible to give an inner epithelial lining after the oral cavity and oropharyngeal tumor excision. Forty-four of the 50 patients had 100% flap survival with excellent wound healing. All the flaps were harvested in less than 1 h. There were four cases of distal tip desquamation and two patients had complete flap necrosis. Distal flap desquamation was observed in SCFs used for resurfacing the external skin defects after oral cavity tumor ablation and needed only conservative treatment measures. Total flap failure was encountered in two patients who had failed in previous chemoradiotherapy for squamous cell cancer of the floor of mouth and tonsil, respectively, and the SCF was used in mucosal defect closure after tumor ablation. The benefits of a pedicled fasciocutaneous supraclavicular flap are clear; it is thin, reliable, easy, and quick to harvest. In head, face and neck reconstructions, it is a good alternative to free fasciocutaneous flaps, regional pedicled myocutaneous flaps, and the deltopectoral flap.

New insights into the role of PPARs.

Peroxisome proliferator-activated receptors (PPARs) are fatty acid-activated transcription factors belonging to the nuclear hormone receptor family. While PPARs are best known as regulators of energy homeostasis, evidence also has accumulated recently for their involvement in basic cellular functions. We review novel insights into PPAR functions in skin wound healing and liver, with emphasis on PPARβ/δ and PPARα, respectively. Activation of PPARβ/δ expression in response to injury promotes keratinocyte survival, directional sensing, and migration over the wound bed. In addition, interleukin (IL)-1 produced by the keratinocytes activates PPARβ/δ expression in the underlying fibroblasts, which hinders the mitotic activity of keratinocytes via inhibition of IL-1 signaling. Initially, roles were identified for PPARα in fatty acid catabolism. However, PPARα is also involved in downregulating many genes in female mammals. We have elucidated the mechanism of this repression, which requires sumoylation of PPARα. Physiologically, this control confers protection against estrogen-induced intrahepatic cholestasis.

Critical roles of PPAR beta/delta in keratinocyte response to inflammation.

The immediate response to skin injury is the release of inflammatory signals. It is shown here, by use of cultures of primary keratinocytes from wild-type and PPAR beta/delta(-/-) mice, that such signals including TNF-alpha and IFN-gamma, induce keratinocyte differentiation. This cytokine-dependent cell differentiation pathway requires up-regulation of the PPAR beta/delta gene via the stress-associated kinase cascade, which targets an AP-1 site in the PPAR beta/delta promoter. In addition, the pro-inflammatory cytokines also initiate the production of endogenous PPAR beta/delta ligands, which are essential for PPAR beta/delta activation and action. Activated PPAR beta/delta regulates the expression of genes associated with apoptosis resulting in an increased resistance of cultured keratinocytes to cell death. This effect is also observed in vivo during wound healing after an injury, as shown in dorsal skin of PPAR beta/delta(+/+) and PPAR beta/delta(+/-) mice.

LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis.

Corneal integrity and transparency are indispensable for good vision. Cornea homeostasis is entirely dependent upon corneal stem cells, which are required for complex wound-healing processes that restore corneal integrity following epithelial damage. Here, we found that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is highly expressed in the human holoclone-type corneal epithelial stem cell population and sporadically expressed in the basal cells of ocular-surface epithelium. In murine models, LRIG1 regulated corneal epithelial cell fate during wound repair. Deletion of Lrig1 resulted in impaired stem cell recruitment following injury and promoted a cell-fate switch from transparent epithelium to keratinized skin-like epidermis, which led to corneal blindness. In addition, we determined that LRIG1 is a negative regulator of the STAT3-dependent inflammatory pathway. Inhibition of STAT3 in corneas of Lrig1-/- mice rescued pathological phenotypes and prevented corneal opacity. Additionally, transgenic mice that expressed a constitutively active form of STAT3 in the corneal epithelium had abnormal features, including corneal plaques and neovascularization similar to that found in Lrig1-/- mice. Bone marrow chimera experiments indicated that LRIG1 also coordinates the function of bone marrow-derived inflammatory cells. Together, our data indicate that LRIG1 orchestrates corneal-tissue transparency and cell fate during repair, and identify LRIG1 as a key regulator of tissue homeostasis.

Kinase signaling cascades that modulate peroxisome proliferator-activated receptors.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in lipid and glucose homeostasis, inflammation and wound healing. In addition to ligand binding, phosphorylation can also regulate PPARs; the biological effects of phosphorylation depend on the stimulus, the kinase, the PPAR isotype, the residue modified, the cell type and the promoter investigated. The study of this dual regulation mode, which allows PPARs to integrate signals conveyed by lipophilic ligands with those coming from the plasma membrane, may ultimately offer new therapeutic strategies.

Benefits of endoscopic vein harvesting.

The purpose of this study was to evaluate and compare the benefits of endoscopic saphenous vein harvesting (EVH) with the traditional incision technique (TIT) for coronary artery bypass grafting (CABG) in respect to the technical procedure and clinical outcome. In a prospective nonrandomized, case-matched study the greater saphenous vein was harvested for CABG in 22 patients using the endoscopic technique and in 18 patients with the traditional method. Comparisons were made for the operating time, length of incision and vein harvested, graft quality, postoperative complications, and pain assessment. Patient demographics were well matched. EVH required smaller incisions than did the TIT (10.5 +/- 6.6 vs. 31.2 +/- 7.8 cm, respectively; p < 0.0001). Harvest time and vein quality were comparable in the two groups. Total vein operating time was shorter following the endoscopic technique (60 +/- 24 vs. 100 +/- 35 minutes, respectively; p < 0.0001). EVH had fewer complications (NS), and postoperative pain was significantly less (p = 0.0034). The major advantages of endoscopic vein harvesting are a significant reduction of postoperative pain and strikingly better cosmetic results. Wound complications seem to be less frequent.