C-reactive protein (CRP) is the prototypic acute-phase reactant that has long been recognized almost exclusively as a marker of inflammation and predictor of cardiovascular risk. However, ...accumulating evidence indicates that CRP is also a direct pathogenic pro-inflammatory mediator in atherosclerosis and cardiovascular diseases. The ‘CRP system’ consists of at least two protein conformations with distinct pathophysiological functions. The binding of the native, pentameric CRP (pCRP) to activated cell membranes leads to a conformational change resulting in two highly pro-inflammatory isoforms, pCRP* and monomeric CRP (mCRP). The deposition of these pro-inflammatory isoforms has been shown to aggravate the localized tissue injury in a broad range of pathological conditions including atherosclerosis and thrombosis, myocardial infarction, and stroke. Here, we review recent findings on how these structural changes contribute to the inflammatory response and discuss the transitional changes in the structure of CRP as a novel therapeutic target in cardiovascular diseases and overshooting inflammation.
C-reactive protein (CRP) is a pentraxin that has long been employed as a marker of inflammation in clinical practice. Recent findings brought up the idea of CRP to be not only a systemic marker but ...also a mediator of inflammation. New studies focused on structural changes of the plasma protein, revealing the existence of two distinct protein conformations associated with opposed inflammatory properties. Native, pentameric CRP (pCRP) is considered to be the circulating precursor form of monomeric CRP (mCRP) that has been identified to be strongly proinflammatory. Recently, a dissociation mechanism of pCRP has been identified on activated platelets and activated/apoptotic cells associated with the amplification of the proinflammatory potential. Correspondingly, CRP deposits found in inflamed tissues have been identified to exhibit the monomeric conformation by using conformation-specific antibodies. Here we review the current literature on the causal role of the dissociation mechanism of pCRP and the genesis of mCRP for the amplification of the proinflammatory potential in inflammatory reactions such as atherosclerosis and ischemia/reperfusion injury. The chance to prevent the formation of proinflammatory mediators in ubiquitous inflammatory cascades has pushed therapeutic strategies by targeting pCRP dissociation in inflammation. In this respect, the development of clinically applicable derivatives of the palindromic compound 1,6-bis(phosphocholine)-hexane (1,6-bis PC) should be a major focus of future CRP research.
Anterolateral thigh (ALT) and gracilis muscle flaps have been described as comparable reconstructive options regarding maximal flap dimension and indications. However, split-thickness skin-grafted ...muscle flaps are generally believed to be inferior to perforator flaps regarding the esthetic outcome of the recipient site. The purpose of this study was to challenge this assumption, comparing the long-term esthetic outcome of the gracilis and the ALT flap.
One hundred forty-eight patients who had undergone free flap reconstruction with either free split-thickness skin-grafted gracilis muscle flaps (n = 86) or ALT flaps (n = 62) were evaluated in the study. Patients' satisfaction with the esthetic outcome, rates of flap loss, wound healing disorders and the necessity for thinning the flap or scar correction procedures were assessed.
Flap loss occurred in 4 of 86 gracilis flaps (4.7%) and 2 of 62 (3.2%) ALT flaps (p > .9999). Thinning or scar correction procedures were necessary for 6 of 86 gracilis (7.0%) and 4 of 62 (6.5%; p > .9999) ALT flap recipient sites. Regarding the overall patients' satisfaction with the esthetic outcome, scores were similar in both groups (2.667 ALT vs. 2.348 gracilis; p = .3739). Contour deformity, scar hypertrophy, and difference in flap color/texture in relation to the surrounding skin were comparable throughout the ALT and gracilis group (2.667 vs. 2.174, p = .2099; 3.333 vs. 2.739, p = .0912 and 2.500 vs. 2.174, p = .3159, respectively).
The gracilis and ALT flap are two equivalent reconstructive options regarding the esthetic outcome of the recipient site and long-term patient satisfaction.
Microvesicles are small vesicles expressing specific antigens from their cells of origin. Elevated levels of microvesicles have been shown to be associated with coagulation disorders as well as with ...different types of malignancies. This study aims to evaluate a possible correlation of different microvesicle subpopulations with a positive history of venous thromboembolism (VTE) in patients with soft tissue sarcoma.
Annexin V - positive microvesicles, leukocyte (CD45-positive), platelet (CD61-positive), activated platelet (CD62P-, CD63-positive), endothelium-derived (CD62E-positive) and tissue-factor (CD142-positive) microvesicles were identified in the peripheral blood of patients with soft tissue sarcoma (n = 39) and healthy controls (n = 17) using fluorescence-activated cell sorting (FACS).
Both the total amount of Annexin V-positive microvesicles and levels of endothelium-derived (CD62E-positive) microvesicles were shown to decrease significantly after tumor resection (n = 18, p = 0.0395 and p = 0.0109, respectively). Furthermore, the total amount of Annexin V - positive microvesicles as well as leukocyte (CD45-positive) and endothelium-derived (CD62E-positive) microvesicles were significantly higher in patients with grade 3 (G3) soft tissue sarcoma (n = 9) compared to healthy controls (n = 17) (p = 0.0304, p = 0.0254 and p = 0.0357, respectively). Moreover, patients with G3 soft tissue sarcoma (n = 9) presented higher levels of Annexin V-positive and endothelium-derived (CD62E-positive) microvesicles compared to patients with grade 2 (G2) soft tissue sarcoma (n = 8) (p = 0.0483 and p = 0.0045). Patients with grade 1 (G1) soft tissue sarcoma (n = 3) presented with significantly lower levels of platelet (CD61-positive) microvesicles than patients with G3 soft tissue sarcoma (n = 9) (p = 0.0150). In patients with a positive history of VTE (n = 11), significantly higher levels of activated platelet (CD62P- and CD63-positive) microvesicles (p = 0.0078 and p = 0.0450, respectively) were found compared to patients without a history of VTE (n = 28).
We found significantly higher levels of Annexin V-positive and endothelium-derived (CD62E-positive) microvesicles to be circulating in the peripheral blood of patients with G3 soft tissue sarcoma compared to patients with G2 soft tissue sarcoma. Furthermore, we showed that high counts of activated platelet-derived microvesicles correlate with the occurrence of VTE. Thus, the detection of these microvesicles might be an interesting new tool for early diagnosis of soft tissue sarcoma patients with increased risk for VTE, possibly facilitating VTE prevention by earlier use of thromboprophylaxis.
Summary Background We recently established negative pressure wound therapy (NPWT) as a safe postoperative care concept for free muscle flaps; however, the molecular effects of NPWT on free muscle ...flaps remain elusive. Here we investigated the effects of NPWT on pathological changes associated with ischaemia/reperfusion injury in free flap tissue. Methods From July 2008 to September 2010, 30 patients receiving skin-grafted free muscle transfer for defect coverage were randomly assigned to two treatment groups: In one group the skin-grafted free flap was covered by a vacuum dressing (NPWT); in the second group, flaps were covered by conventional petroleum gauze dressings (conv). Biopsies were taken intra-operatively prior to clipping of the pedicle and on postoperative day 5. Samples were analysed by immunohistochemistry for infiltration of inflammatory cells, real-time polymerase chain reaction (RT-PCR) for the analysis of expression levels of interleukin-1β (IL-1β) and tumour necrosis factor (TNF)-alpha as markers of inflammation. Histological samples were also examined for interstitial oedema formation, and apoptosis was detected by a terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Results NPWT leads to a significantly reduced tissue infiltration of CD68 + macrophages and reduced expression of the inflammatory cytokines IL-1β and TNFα. None of these parameters was significantly elevated in the pre-ischaemic biopsies. Furthermore, NPWT reduced the interstitial oedema formation and the number of apoptotic cells in free flap tissue. Conclusion NPWT of skin-grafted free muscle flaps leads to a reduced inflammatory response following ischaemia/reperfusion, resulting in reduced oedema formation improving the microcirculation and ultimately reduced tissue damage. We thereby deliver new insight into the effects of NPWT.
Summary Background Throughout literature, there are different parameters defining the ideal shape of the lip and lower third of the face. This study was conducted to clarify what it is that makes ...lips attractive – and whether there are gender-related differences of an attractive lip and lower third of the face. Patients and methods Pictures of the lip and chin region of 176 patients were photographed in a standardised way and evaluated by 250 voluntary judges through an internet presentation by means of an analogue Likert scaling system. Results We found a significant higher ratio of upper vermillion height/mouth-nose distance in frontal-view images of attractive compared to unattractive female (p < 0.001) and male (p < 0.05) perioral regions. Furthermore, the ratio of upper vermillion height/chin-nose distance was significantly higher in attractive than in unattractive female (p < 0.005) and male (p < 0.05) lip and chin regions. The nasolabial angle was significantly sharper in attractive compared to unattractive female perioral regions (p < 0.001). Moreover, attractive female lip and chin regions showed a wider mentolabial angle compared to unattractive female lip and chin regions (p < 0.05). Comparing men and women, we found that attractive female perioral regions showed a higher ratio of lower vermillion height/chin-mouth distance (p < 0.05) and lower vermillion height/chin-nose distance than attractive male perioral regions (p < 0.05). Conclusion We were able to define certain parameters of the lip and lower third of the face that seem to add to the attractivity of female and male individuals and prove that there are gender-related differences in form and shape of an attractive lower third of the face.
Distal lower extremity reconstruction can be challenging in terms of flap design. Bulky flaps result in limited mobility accompanied with the need of customized footwear. Raising the ALT-flap in a ...superficial fascial plane (thin ALT-flap) can be beneficial. This study evaluates thin ALT-flaps for lower distal extremity reconstruction.
In a retrospective study, patients that underwent microvascular extremity reconstruction at the level of the ankle and dorsal foot at the University of Freiburg from 2008-2018 were reviewed.
95 patients could be included in the study (35 perforator flaps, 8 fascia flaps and 54 muscle flaps).Among the perforator flaps, 21 ALT-flaps were elevated conventionally and 14 in the superficial fascial plane (thin ALT-flap). Among the conventional ALT-flaps, there was one flap loss (5%) and one successful revision (5%). 5(24%) flaps received secondary thinning. 57%(
= 12) were able to wear conventional footwear. There were 2(15%) successful revisions of thin ALT-flaps. 100% of thin ALT-flaps survived and 85%(
= 11) of the patients wore ordinary footwear after defect coverage.Among fascial flaps, 50%(
= 4) had to be revised with 2(25%) complete and 1 (13%) partial flap loss. All patients achieved mobility in ordinary shoes (
= 8).In muscle flaps, there were 7(13%) revisions and 5(9%) flap losses. 5(9%) flaps received secondary thinning. Only 33%(
= 18) were mobile in ordinary footwear.
The thin ALT-flap is a save one-stage evolution for lower distal extremity reconstruction with a favorable flap survival rate. Compared with conventional ALT-flaps it might be beneficial in reducing the need for expensive custom fitted shoes and secondary thinning procedures.
Liposarcoma constitute about 13% of all soft tissue sarcoma and are associated with a high risk of metastases. As the preoperative differentiation between benign and malign lipomatous tumors is ...restricted to magnetic resonance imaging, computed tomography and biopsy, we performed a miRNA array to distinguish dedifferentiated liposarcoma patients from healthy controls and lipoma patients.
Blood samples of patients with dedifferentiated liposarcoma, healthy controls and lipoma patients were collected. Whole blood RNA was extracted and samples of patients with dedifferentiated liposarcoma (n= 6) and of healthy donors (n= 4) were analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. qRT-PCR was carried out to confirm the most differentially expressed miRNA; being further analyzed in an independent cohort of healthy controls as well as in lipoma patients.
As shown by the microarray, two miRNAs (miR-3613-3p, miR-4668-5p) were shown to be significantly upregulated (fold change: > 2.5; p< 0.05) in patients with dedifferentiated liposarcoma (n= 6) as compared to healthy controls (n= 4). miR-3613-3p was further validated by qRT-PCR to be significantly upregulated in dedifferentiated liposarcoma patients compared to an independent cohort of healthy controls (n= 3) and lipoma patients (n= 5).
We identified a specific whole blood miRNA (miR-3613-3p) that may serve to distinguish between dedifferentiated liposarcoma patients and healthy controls, thus potentially serving as a specific biomarker for dedifferentiated liposarcoma.
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