Purpose
This study aims to assess the effectiveness of Microfragmented Autologous Fat Tissue (MFAT) treatment for knee osteoarthritis and to investigate whether patients’ pre-treatment clinical ...condition, such as synovitis, correlates with clinical outcomes, to identify potential predicting factors for the success or failure of the treatment.
Methods
In this prospective Cohort Study Level II multicentric trial, consecutive patients with a diagnosis of early/mild osteoarthritis and failure of previous conservative measures were enrolled to undergo diagnostic arthroscopy and a single MFAT injection. Patients were assessed with repeated scoring systems at baseline, 6 months, and 12 months after surgery. The demographic features, the arthroscopic findings, the immunophenotype of injected tissue and the histologic examination of synovia of failed patients were analyzed.
Results
Data from 91 patients showed a significant improvement in Lysholm, WOMAC scores at 1-year follow-up (p < 0.001). A significant decrease in VAS score was observed, while a significant improvement of measured flexion angle was registered at 1 year (p < 0.001). No major complications were reported.
Age and synovitis were identified as significant factors influencing the clinical outcome (p < 0.05). Body mass index, previous or concomitant procedures, and specific cartilage defects had no influence. The mean number of injected adipose tissue-derived mesenchymal stem cells seem not to correlate with the clinical outcome.
Conclusion
MFAT is effective in reducing pain when used with a single dose injection in early/mild OA of the knee, without major complications. Age over 60 and synovitis may be predictive for persistent pain at one year and should be considered before indications.
Objectives Anomalous intraosseous venous drainage is a rare and almost unknown entity; only 14 cases have been reported in the literature and 4 mentioned in textbooks. We report the characteristics ...of 35 further cases observed in 32 patients. Method After the presentation of two cases at the congress of the French Society of Phlebology in Paris (2013), 12 colleagues joined to present a large series of so-called bone perforators observed in their practice, all identified with at least a duplex investigation. Results Thirty-two patients suffering from varicose veins and/or skin changes (C
-C
) associated with a bone perforator of the tibia (with bilateral anomalies in three) are reported: 19 females and 13 males, average age 56.9. The majority of the affected legs were symptomatic (30/35). Bone perforator was an isolated finding in 27/35 legs. In three cases, the investigations revealed that the venous reflux in the bone originated from an incompetent posterior tibial vein. Conclusions We suggest the name of "bone perforators" for an anomalous tibial intraosseous venous drainage, feeding varicose veins, and in more advanced stages lipodermatosclerosis and leg ulcers. Most of them were successfully treated with surgery or sclerotherapy.
Genetic experiments established that p63 is crucial for the development and maintenance of pluri-stratified epithelia and KLF4 for the barrier function of the skin. KLF4 is one of the factors that ...reprogram differentiated cells to iPS. We investigated the relationship between p63 and KLF4 using RNA interference, overexpression, chromatin immunoprecipitation and transient transfections with reporter constructs. We find that p63 directly represses KLF4 in normal keratinocytes (KCs) by binding to upstream promoter sites. Unlike p63, KLF4 levels are high in the upper layers of human skin and increase upon differentiation of KCs in vitro. In HaCaT KCs, which harbor two mutant alleles of p53, inactivation of p63 and of mutant p53 leads to KLF4 repression. p63 and p53 mutants are bound to sites in the KLF4 core promoter. Importantly, expression of the H179Y and R282Q p53 mutants in primary KCs is sufficient to activate endogenous KLF4. Finally, immunohistochemical analysis of tissue arrays confirms increased coexpression of KLF4 and mutant p53 in squamous cell carcinomas. Our data indicate that suppression of KLF4 is part of the growth-promoting strategy of p63 in the lower layers of normal epidermis, and that tumor-predisposing p53 mutations hijack p63 to a different location on the promoter, turning it into an activator of this reprogramming factor.
The transcription factor p63, member of the p53 family, is crucial for epithelial development. An RNAi screening identified the apoptotic gene Procaspase-8 as a target activated by p63. The caspase-8 ...inhibitor FLIP is also under p63 control. We analysed and detailed the direct transactivation through the use of RNAi, reporter assays, ChIPs, western blots, confocal studies in HaCat, as well as in primary human keratinocytes. The direct DeltaNp63 regulation of these targets was confirmed in vivo using transgenic DeltaNp63 mice under the K5 promoter, as compared with p63 knockout mice, and in vitro in normal human primary keratinocytes following UV irradiation. Lowering the steady state of p63 protein levels changes the relative ratio of FLIP isoforms, causing the activation of the expressed, inactive Procaspase-8, into the active isoform thus triggering the proapoptotic cascade. Therefore, p63 fine-tunes the Procaspase-8-FLIP pro- and antiapoptotic pathway in keratinocytes.
Summary
Background Primary cutaneous T‐cell lymphomas (CTCLs) are a heterogeneous group of lymphomas where the tumour population emerges within a multiple subclone pattern. Mycosis fungoides (MF) ...and Sézary syndrome (SS) are characterized by the expansion of clonal CD4+/CD45RO+ memory T cells. Lymphomatoid papulosis (LyP) is a chronic, lymphoproliferative disorder included in the CD30+ primary CTCL spectrum. Several studies have suggested a role of viral infection for super‐antigenic activation of T lymphocytes; however, evidence of their association with CTCLs is still lacking. Human herpesvirus (HHV) 7 is a CD4+ T‐lymphotropic herpesvirus; its restricted cellular tropism and the ability to induce cytokine production in infected cells could make it an important pathogenic cofactor in lymphoproliferative disorders.
Objectives To investigate the presence of HHV7 DNA on CTCL and healthy skin donors (HD).
Methods We used quantitative real time polymerase chain reaction to evaluate the potential pathogenic role of HHV7.
Results Twenty‐seven of 84 (32·1%) HD were positive for HHV7 DNA. Twenty‐one of 148 (14·2%) patients with CTCLs were positive for HHV7 DNA: nine of 39 (23·1%) SS, six of 14 (42·9%) CD30+ CTCLs and six of 24 (25·0%) LyP, and HHV7 DNA was negative in all 71 patients with MF.
Conclusions These results seem to exclude a pathogenic role of HHV7 in CTCLs, suggesting the possibility of skin as a latency site.
p63 is a developmentally regulated transcription factor related to p53. It is involved in the development of ectodermal tissues, including limb, skin and in general, multilayered epithelia. The ...ΔNp63α isoform is thought to play a ‘master’ role in the asymmetric division of epithelial cells. It is also involved in the pathogenesis of several human diseases, phenotypically characterized by ectodermal dysplasia. Our understanding of transcriptional networks controlled by p63 is limited, owing to the low number of bona fide targets. To screen for new targets, we employed chromatin immunoprecipitation from keratinocytes (KCs) coupled to the microarray technology, using both CpG islands and promoter arrays. The former revealed 96 loci, the latter yielded 85 additional genes. We tested 40 of these targets in several functional assays, including: (i) in vivo binding by p63 in primary KCs; (ii) expression analysis in differentiating HaCaT cells and in cells overexpressing ΔNp63α; (iii) promoter transactivation and (iv) immunostaining in normal tissues, confirming their regulation by p63. We discovered several new specific targets whose functional categorization links p63 to cell growth and differentiation.
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