Diabeetikon jalkojen tutkiminen kolmessa minuutissa

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Local C-Reactive Protein Expression in Obliterative Lesions and the Bronchial Wall in Posttransplant Obliterative Bronchiolitis

The local immunoreactivity of C-reactive protein (CRP) was studied in a heterotopic porcine model of posttranplant obliterative bronchiolitis (OB). Bronchial allografts and control autografts were examined serially 2–28 days after subcutaneous transplantation. The autografts stayed patent. In the allografts, proliferation of inflammatory cells (P < .0001) and fibroblasts (P = .02) resulted in occlusion of the bronchial lumens (P < .01). Influx of CD4+ (P < .001) and CD8+ (P < .0001) cells demonstrated allograft immune response. CRP positivity simultaneously increased in the bronchial walls (P < .01), in macrophages, myofibroblasts, and endothelial cells. Local CRP was predictive of features characteristic of OB (R = 0.456–0.879, P < .05−P < .0001). Early obliterative lesions also showed CRP positivity, but not mature, collagen-rich obliterative plugs (P < .05). During OB development, CRP is localized in inflammatory cells, myofibroblasts and endothelial cells probably as a part of the local inflammatory response

Statistical analysis plan for the 5-year and 10-year follow-up assessments of the FIDELITY trial

Background: The research objectives of the 5-year and 10-year assessments in the Finnish degenerative meniscal lesion study (FIDELITY) are twofold: (1) to assess the long-term efficacy of arthroscopic partial meniscectomy (APM) in adults (age 35 to 65 years) with a degenerative meniscus tear and (2) to determine the respective effects of APM and degenerative meniscus tear on the development of radiographic and clinical knee osteoarthritis (OA). Methods and design: FIDELITY is an ongoing multi-center, randomized, participant and outcome assessor blinded, placebo-surgery-controlled trial in 146 patients. This statistical analysis plan (SAP) article describes the overall principles for analysis of long-term outcomes (5-year and 10-year follow up), including how participants will be included in each analysis, the primary and secondary outcomes and their respective analyses, adjustments for covariates, and the presentation of the results. In addition, we will present the planned sensitivity and subgroup analyses. Discussion: To assess the long-term efficacy of APM on knee symptoms and function we are carrying out a long-term (5-year and 10-year) follow up of our placebo-surgery-controlled FIDELITY trial according to statistical principles outlined in detail in this document. As our second primary objective, whether APM (resection of torn meniscus tear) accelerates or delays the development of knee osteoarthritis in patients with an arthroscopically verified degenerative tear of the medial meniscus, a pre-registered follow-up is also carried out. Trial registration: ClinicalTrials.gov, NCT00549172 (Arthroscopy in the Treatment of Degenerative Medial Meniscus Tear). Registered on 25 October 2007 (NCT00549172). ClinicalTrials.gov, NCT01052233 (Development of Knee Osteoarthritis After Arthroscopic Partial Resection of Degenerative Meniscus Tear). Registered on 20 January 2010.publishedVersionPeer reviewe

Arthroscopic partial meniscectomy versus placebo surgery for a degenerative meniscus tear : a 2-year follow-up of the randomised controlled trial

Objective To assess if arthroscopic partial meniscectomy (APM) is superior to placebo surgery in the treatment of patients with degenerative tear of the medial meniscus. Methods In this multicentre, randomised, participant-blinded and outcome assessor-blinded, placebo-surgery controlled trial, 146 adults, aged 35-65 years, with knee symptoms consistent with degenerative medial meniscus tear and no knee osteoarthritis were randomised to APM or placebo surgery. The primary outcome was the between-group difference in the change from baseline in the Western Ontario Meniscal Evaluation Tool (WOMET) and Lysholm knee scores and knee pain after exercise at 24 months after surgery. Secondary outcomes included the frequency of unblinding of the treatment-group allocation, participants' satisfaction, impression of change, return to normal activities, the incidence of serious adverse events and the presence of meniscal symptoms in clinical examination. Two subgroup analyses, assessing the outcome on those with mechanical symptoms and those with unstable meniscus tears, were also carried out. Results In the intention-to-treat analysis, there were no significant between-group differences in the mean changes from baseline to 24 months in WOMET score: 27.3 in the APM group as compared with 31.6 in the placebo-surgery group (between-group difference, -4.3; 95% CI, -11.3 to 2.6); Lysholm knee score: 23.1 and 26.3, respectively (-3.2; -8.9 to 2.4) or knee pain after exercise, 3.5 and 3.9, respectively (-0.4; -1.3 to 0.5). There were no statistically significant differences between the two groups in any of the secondary outcomes or within the analysed subgroups. Conclusions In this 2-year follow-up of patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear, the outcomes after APM were no better than those after placebo surgery. No evidence could be found to support the prevailing ideas that patients with presence of mechanical symptoms or certain meniscus tear characteristics or those who have failed initial conservative treatment are more likely to benefit from APM.Peer reviewe

Cox-2, tenascin, CRP, and ingraft chimerism in a model of post-transplant obliterative bronchiolitis

Chronic rejection in the form of obliterative bronchiolitis (OB) is the major cause of death 5 years after lung transplantation. The exact mechanism of OB remains unclear. This study focused on the role of cyclo-oxygenase (COX) -2, tenascin, and C-reactive protein (CRP) expression, and the occurrence of ingraft chimerism (= cells from two genetically distinct individuals in a same individual) in post-transplant OB development. In our porcine model, OB developed invariably in allografts, while autografts stayed patent. The histological changes were similar to those seen in human OB. In order to delay or prevent obliteration, animals were medicated according to certain protocol. In the beginning of the bronchial allograft reaction, COX-2 induction occurred in airway epithelial cells prior to luminal obliteration. COX-2 expression in macrophages and fibroblasts paralleled the onset of inflammation and fibroblast proliferation. This study demonstrated for the first time, that COX-2 expression is associated with the early stage of post- transplant obliterative airway disease. Tenascin expression in the respiratory epithelium appeared to be predictive of histologic features observed in human OB, and influx of immune cells. Expression in the bronchial wall and in the early obliterative lesions coincided with the onset of onset of fibroblast and inflammatory cell proliferation in the early stage of OB and was predictive of further influx of inflammatory and immune cells. CRP expression in the bronchial wall coincided with the remodelling process. High grade of bronchial wall CRP staining intensity predicted inflammation, accelerated fibroproliferation, and luminal obliteration, which are all features of OB. In the early obliterative plaque, majority of cells expressed CRP, but in mature, collagen-rich plaque, expression declined. Local CRP expression might be a response to inflammation and it might promote the development of OB. Early appearance of chimeric (= recipient-derived) cells in the graft airway epithelium predicted epithelial cell injury and obliteration of the bronchial lumen, which both are features of OB. Chimeric cells appeared in the airway epithelium after repair following transplantation-induced ischemic injury. Ingraft chimerism might be a mechanism to repair alloimmune-mediated tissue injury and to protect allografts from rejection after transplantation. The results of this study indicate, that COX-2, tenascin, CRP, and ingraft chimerism have a role in OB development. These findings increase the understanding of the mechanisms of OB, which may be beneficial in further development of diagnostic options.Merkittävin keuhkonsiirron tuloksia rajoittava tekijä on krooninen hyljintäreaktio, joka ilmenee keuhkossa pieniä ilmateitä tukkeuttavana sidekudoskasvuna, obliteroivana bronkioliittina (OB). Sen synnyssä keskeinen tekijä on immunologisesti aktiivisten tulehdussolujen aiheuttama hengitystie-epiteelivaurio. Intensiivisestä tutkimuksesta huolimatta tähän komplikaatioon ei ole olemassa parantavaa hoitoa. Väitöskirjatyön tarkoituksena oli tutkia proteiinien COX-2, tenaskiini ja CRP ilmentymistä kokeellisessa OB:ssä. Näitä proteiineja oli aikaisemmin havaittu sairaustiloissa, joissa vallitsee tulehdus ja kiihtynyt sidekudoskasvu. OB:ssä niitä ei ollut aiemmin tutkittu. Lisäksi tutkimme kimerismiä, eli vastaanottajan solujen vaeltamista siirteeseen. Tarkoituksena oli selvittää, korjautuuko siirteen tuhoutunut epiteelisolukko vastaanottajan omilla soluilla, ja lisääkö kimerismi siirteen siedettävyyttä. Tutkimuksessa käytettiin ryhmämme aikaisemmin kehittämää koe-eläinmallia, jossa sian vatsanahkaan istutetaan pieniä ääreiskeuhkoputken paloja. Tässä mallissa sialta toiselle istutettuihin siirrännäisiin kehittyy obliteraatio, joka vastaa histologialtaan ihmisen OB:a. Lääkityksellä obliteraatiota pystytään hidastamaan ja tarvittaessa estämään kokonaan. COX-2 eritys liittyi obliteraation varhaisvaiheeseen. COX-2 värjäytyminen hengitystie-epiteelissä edelsi obliteratiivisten muutosten kehittymistä, ja se ajoittui aktiivisen tulehduksen ja sidekudoskasvun vaiheeseen. Tenaskiinin värjäytyminen epiteelissä ennusti obliteratiivisten muutosten kehittymistä. Keuhkoputken seinämässä ja varhaisessa sidekudostulpassa se puolestaan ennusti lisääntyvää inflammaatiota. CRP värjäytyi keuhkoputken seinämässä ja varhaisessa sidekudostulpassa aktiivisen kudosmuovautumisen aikana. Sidekudostulpan kypsyessä CRP eritys väheni. Paikallinen CRP eritys saattaa olla vaste tulehdukselle ja se saattaa edesauttaa OB:n kehittymistä. Kimerismi ennusti epiteelivauriota ja pienten ilmateiden tukkeutumista. Kimerismiä havaittiin vaurioituneessa epiteelissä, mikä viittaa siihen, että kimerismi saattaa olla mekanismi joka korjaa hyljjintäreaktioon liittyvää kudosvauriota ja suojaa siirrännäistä hyljinnän aiheuttamalta tuhoutumiselta. Tutkimus osoitti, että proteiineilla COX-2, tenaskiini, ja CRP on aktiivinen rooli OB:n synnyssä, ja että ainakin osa siirrännäisen hengitystie-epiteelistä näyttää korjautuvan vastaanottajan kimeerisillä soluilla

Diabetesjalan virheasento : leikatako vai ei?

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