Introduction: Involvement of the forefoot is common among patients with Rheumatoid Arthritis. It results in severe deformities with significant disabilities. Aim: The aim of this study was to compare and assess in patients with Rheumatoid Arthritis in a South African population the outcomes of severe forefoot deformity reconstruction surgery in the short- to medium-term and in particular focusing on radiological, clinical, and functional outcomes. Patients and Methods: A retrospective review of 19 patients who received reconstructive forefoot surgery for forefoot deformities resulting from Rheumatoid Arthritis was undertaken. They all underwent Modified Hoffman Surgical Reconstruction (first MTPJ fusion and lesser toe resection arthroplasty). The patient records between 2013 and 2016 were reviewed. Pre-operative and post-operative outcome scores were collected. Final postoperative radiographs were analyzed. Patients completed Short Form 36 and AOFAS forefoot scores. Post-operative scores were collected 6 months post-op. Results: There were 19 patients in the study with a minimum 6 months follow up. Of the 19 patients 17 (89.5%) were females and 2 (10.5%) males. The mean age was 54.9 ± 9.6 years (range: 34 – 69 years). Most patient outcomes (SF36, AOS alignment, VAS Pain percentage, and VAS Disability percentage) significantly improved with a p value < 0.05, when comparing the pre-operative versus post-operative variable scores. However, only AOS Alignments showed no significant difference between pre-operative and post-operative scores (p>0.05). Conclusion: Reconstructive forefoot surgery with the Modified Hoffman Surgical Reconstruction provides marked radiological correction, with significant improvements in the quality of life of the cohort of patients.

Psoriatic disease (PD) is an autoimmune disease that affects millions of women and currently has no cure. Examining the lived experience of women with PD who choose to treat their disease with alternative methods may allow for deeper understanding of how mental health professionals can support their choices. Using phenomenology, this study looked at the experiences of these women through theories of self-efficacy and self-in-relation theory, theories that empower and speak to women. The participants consisted of women who reported a diagnosis of PD, who reported they had abstained from pharmaceutical interventions for at least the previous six months. The sample size consisted of 7 participants, recruited through social media, from various parts of the world. Explication was used to assess the data and consisted of the following: bracketing and phenomenological reduction, delineating units of meaning, clustering of units of meaning to form themes, summarizing each interview, and extracting general and unique themes from all interviews and making a composite summary. The findings of this study showed that the participants reported feeling capable of pursuing health options that aligned with their values and were not opposed to pharmaceutical options at some point. In addition, findings indicated participants felt minimal, if any, support from their medical care providers. The results of the study may facilitate positive social change by informing women with PD about the benefits of taking an active role in treatment planning. Further, this study'€™s results may expand knowledge about treatment of women with PD and inform medical professionals, specifically mental health professionals, about what is important to these women in terms of a treatment plan.

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Lyme disease is the most common vector-borne disease in the United States with over 20,000 cases reported yearly. A common and sometimes severe symptom of Lyme disease is Lyme arthritis, which has clinical and etiological similarities to rheumatoid arthritis. While risk factors for Lyme disease are established, there have been no studies exploring risk factors for Lyme arthritis. To assess this relationship a cross-sectional study was conducted, using data from confirmed cases of Lyme disease reported to the Massachusetts Department of Public Health (MDPH) from 2000 to 2006. Bivariate analyses and ANOVA tests were conducted to assess the relationship between age, sex and Lyme arthritis, as well as other symptoms of Lyme disease. Results showed that those in the lowest quartile of age were more likely to be diagnosed with Lyme arthritis alone than those in higher age quartiles (p <0.001). No significant difference was seen in the proportion of Lyme arthritis diagnosis between males and females (p = 0.61). By recognizing that younger patients with Lyme disease are more likely to be diagnosed with Lyme arthritis, measures may be taken to improve early identification and treatment of Lyme disease in this group. We recommend that a future prospective study be conducted to further elucidate the true relationships between age, sex, and Lyme arthritis.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24190号 / 医博第4884号 / 新制||医||1060(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊藤 能永, 教授 安達 泰治, 教授 椛島 健治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Die Rheumatoide Arthritis ist eine chronische Autoimmunerkrankung, deren Pathogenese noch unvollständig verstanden ist. Eine Dysbalance von pro- und antiinflammatorischen T-Helferzellen ist an der Entzündungsreaktion wesentlich beteiligt. Die Rolle von proinflammatorischen Th17-Zellen und regulatorischen Tregs ist bereits recht gut erforscht und bietet bereits erfolgreiche Therapieansätze. Umstritten bleibt die Rolle der sogenannten Th9-Zellen, welche pro- und antiinflammatorische Wirkungen zu vereinen scheinen. Die vorliegende Untersuchung umfasst die Daten von 7 RA-Patientinnen und -Patienten und 10 gesunden Kontrollen. Nach Isolation von naiven CD4+ T-Zellen erfolgte eine durchflusszytometrische Phänotypisierung der T-Zellen. Diese Phänotypisierung zeigte keinen relevanten Unterschied zwischen Pat und HD. Im Anschluss an eine 3-tägige Zellkultur von naiven und nicht naiven CD4+ T-Zellen unter Th9- und Th17-Stimulation erfolgte eine Auswertung mittels Durchflusszytometrie, RT-PCR und ELISA. Hierbei wurde eine sehr ähnliche Wirkung beider Stimuli auf die T-Zelldifferenzierung, die Zytokinproduktion und die Expression von Oberflächenmarkern beobachtet. Insbesondere die IL-9-Produktion wurde durch beide Stimuli signifikant induziert. Es scheint, dass IL-9-produzierende Zellen durch unterschiedliche Differenzierungswege induziert werden. Dies unterstützt die kontroverse Hypothese, dass Th9-Zellen keinen eigenständigen T-Helferzellsubtyp darstellen. Im Vergleich zu den Pat in Remission war die induzierte Zytokinproduktion (IL-9, IL-17, IFNγ) bei den HD betont. Dies liegt vermutlich an unspezifischen Effekten durch die immunsuppressive Therapie. Bei den beiden Patientinnen und Patienten mit der höchsten Krankheitsaktivität jedoch wurde die höchste IL-9-Konzentration in den Überständen nach Stimulation festgestellt. Ein IL-9-Exzess bzw. eine IL-9-Blockade hatte keinen signifikanten Einfluss auf die T-Zelldifferenzierung, die Zytokinproduktion und die Expression der Oberflächenmarker und des Transkriptionsfaktors. Das Vorliegen eines relevanten IL-9-regulierenden, autokrinen Mechanismus ist daher unwahrscheinlich. Zusammenfassend ergeben sich Hinweise, dass es sich bei IL-9-produzierenden Zellen aufgrund der diversen Differenzierungswege nicht um einen eigenständige T-Helferzellsubtyp handelt. Es benötigt einen sehr gut ausbalancierten Zytokincocktail und vermutlich eine längere Kulturzeit, um tatsächlich Th9-Zellen zu polarisieren. Ob diese in vivo vorkommen und eine Rolle in der Pathogenese der RA spielen ist zum jetzigen Zeitpunkt ebenso unklar wie die Rolle des IL-9 in der Pathogenese der RA. Daher kommt IL-9 als therapeutisches Ziel nach jetziger Kenntnis nicht in Betracht. / Rheumatoid arthritis is a chronic autoimmune disease whose pathogenesis is not yet fully understood. An imbalance of proinflammatory and anti-inflammatory T helper cells is essential to the inflammatory response. The role of proinflammatory Th17 cells and regulatory T cells has already been researched well and offers successful therapeutic approaches. The role of Th9 cells, which seem to combine proinflammatory and anti-inflammatory effects, remains controversial. The present study includes data from 7 RA patients and 10 healthy controls. T cells were phenotyped by flow cytometry after isolation of naive CD4+ T cells from PBMC. This phenotyping showed no relevant difference between RA patients and HD. Following a 3-day cell culture of naive and non-naive CD4+ T cells under Th9- and Th17-inducing conditions, the evaluation was carried out using flow cytometry, RT-PCR and ELISA. A very similar effect of the Th9- and Th17-stimulus on T-cell differentiation, cytokine production and the expression of surface markers was observed. IL-9 production was significantly induced by both stimuli. It appears that IL-9 producing cells are induced by different pathways of differentiation. This supports the controversial hypothesis that Th9 cells are not an independent Th cell subset. In comparison to RA patients in remission, the induced cytokine production (IL-9, IL-17, IFNγ) was higher in HD. This is probably due to unspecific effects of immunosuppressive therapy. Two patients with the highest disease activity, however, also showed the highest IL-9 concentration in the supernatants after stimulation. Neither an IL-9 excess nor an IL-9 blockade had a significant influence on T-cell differentiation, cytokine production, the expression of surface markers and of the transcription factor PU.1. The existence of a relevant IL-9-regulating autocrine mechanism seems unlikely. In summary, there is evidence that IL-9-producing cells are not an independent Th cell subset. It takes a very well-balanced cytokine cocktail and probably a longer cell culture to polarize actual Th9 cells. Whether Th9 cells occur in vivo and play a role in the pathogenesis of RA remains unclear as well as the role of IL-9 in the pathogenesis of RA. Therefore, according to present knowledge, IL-9 is not an option as a therapeutical target.

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