Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Treatment of Symptomatic Bunionette Deformity with Distal Metatarsal Metaphyseal Osteotomy with no Fixation or Strapping

Category: Lesser Toes; Bunion Introduction/ Purpose: Bunionette deformity (BD) is a painful condition of the fifth metatarsal characterized by an osseous prominence and varus deformity. The purpose of this study is to assess the clinical, functional, and radiographic outcomes of percutaneous distal metatarsal metaphyseal osteotomy (DMMO) without fixation or post-operative strapping of the foot. Methods: A retrospective case series was performed on 111 patients (132 feet) with symptomatic BD who underwent percutaneous DMMO of the fifth metatarsal from September 2020 to January 2022. Patient-reported clinical outcome measures, including the Foot Function Index (FFI) questionnaire, the Visual Analog Score (VAS), and overall satisfaction were collected. Four- Five intermetatarsal angle (IMA) correction, time to bone union, and complication rates were assessed in all patients. Results: The mean post-operative follow-up time was 24.1 months. Both radiographic parameters and patient-reported outcome measures significantly improved after DMMO procedure. The average fourth-to-fifth IMA improved from 12.2 degrees, preoperatively, to 4.4 degrees, postoperatively (p <.001). Pre-operatively, patients had a mean VAS of 7.6, which improved to 0.6 at the last follow-up (p <.001). Furthermore, The average FFI significantly decreased from 19.2 to 4.4 (p <.001). 108 out of 111 patients reported being satisfied with the outcomes of the procedure. Average bone union was achieved at 12.6 weeks post- operation, with a minimum of 12 and a maximum of 25 weeks. The complication rate was 1.5%, including one case of an asymptomatic cock-up deformity and one case of lateral fifth metatarsal shaft bone overhang pain, which resolved with an exostectomy. Conclusion: The results of this study suggest that percutaneous DMMO of the fifth metatarsal without internal fixation or postoperative immobilization or strapping is effective at improving radiographic alignment, pain, function, and overall satisfaction with minimal complication

Effective Treatment of Insertional Achilles Tendinopathy with Minimally Invasive Zadek Osteotomy, Independent of X/Y Ratio

Category: Hindfoot; Ankle Introduction/Purpose: The Zadek osteotomy (ZO) has been demonstrated to be an effective treatment for patients with Haglund deformity and Insertional Achilles Tendinopathy (IAT). Radiographic measurements are one method of diagnostic criteria that have been utilized to define a more specific patient cohort that is a superior candidate for Zadek intervention. Tourné et al. most recently proposed an X/Y 2.5. All patients had a minimum of one-year follow-up (mean 23.24±4.82). Pain, function, and mobility PROMIS scores, VAS scores, complications, X/Y ratio measurements, and calcaneal pitch angle measurement were collected preoperatively and at final follow-up appointment. Cases were placed in cohorts based on preoperative X/Y above or below 2.5). T-tests were used to determine statistical differences following ZO. Similarly, chi-squared analysis was used to compare differences in categorical data between our groups. Results: A summary of preoperative and postoperative PROMIS scores, VAS scores, calcaneal pitch measurements, and X/Y ratios can be found in Table 1. Patients with X/Y 2.5 demonstrated significant improvement in PROMIS pain, VAS, and X/Y ratio (p 2.5, preoperative VAS scores were higher (p=0.014) and improved to a significantly larger degree (p=0.006). There was one case of minor neuropathy (X/Y > 2.5); there was one patient that required revision to open debridement and repair (X/Y < 2.5). We observed a 98% rate of satisfaction overall following ZO intervention. Conclusion: Zadek osteotomy demonstrated improvement in patients’ pain and excellent patient satisfaction, regardless of their preoperative X/Y ratio on radiograph. However, patients with X/Y ratio < 2.5 did demonstrate significant improvement in patient reported function and mobility scores. Overall, a 98% satisfaction was observed following ZO in all patients. Preoperative X/Y ratio did not seem to determine success of ZO in the treatment of IAT, however, further clinical correlation is needed. to better understand differences if PROMIS physical function and mobility in terms of long-term success of the ZO

Dose Severity of Achilles Tendinopathy on Preoperative MRI Predict Functional Outcomes after Minimally Invasive Zadek Osteotomy?

Category: Hindfoot; Ankle Introduction/Purpose: Minimally Invasive Zadek osteotomy (MIS ZO) has been demonstrated to be a safe and effective surgical intervention for patients with Insertional Achilles Tendinopathy (IAT) and Haglund’s deformity. However, there is limited literature to guide surgeons one which patients may be the best candidates for MIS ZO. Severity of IAT on preoperative MRI may correlate with post operative functional outcomes and help guide patient selection for treatment with MIS ZO. The current study evaluated the postoperative outcomes of MIS ZO in patients with various grades of Achilles tendinopathy on preoperative MRI, to determine if severity of disease on preoperative MRI could be predictive of improved functional outcomes after MIS ZO. Methods: Patients who underwent MIS ZO for IAT and Haglund’s deformity were identified and retrospectively analyzed at a mean of 15.59 months follow-up. Achilles pathology was graded as previously described by Nicholson et al. on preoperative MRI. Grade 1 describes anteroposterior diameter of 6-8 mm and nonuniform degeneration; grade 2 describes diameter >8 mm and 8 mm and uniform degeneration of >50% tendon width. Fourteen patients met our inclusion criteria. Four patients exhibited grade 1 pathology preoperatively, 3 patients exhibited grade 2 pathology preoperatively, and 7 patients exhibited grade 3 pathology preoperatively. Preoperative and postoperative Patient Reported Outcome Measurement Information System (PROMIS) scores, complications, and revisions were recorded for each patient. PROMIS scores were compared using a paired t-test. All other continuous data was compared by Analysis of Variance (ANOVA); all categorical data was compared using Chi-squared analysis. P< 0.05 were considered significant. Results: PROMIS pain score improved postoperatively in patients with grade 1 66.75±5.50 to 59.00±7.75, p=0.036) and grade 3 (69.86±6.17 to 55.71±10.44, p=0.011) Achilles tendinopathy on preoperative MRI. Meanwhile, in patients with grade 2 pathology, PROMIS physical function (38.33±8.50 to 43.67±9.07, p=0.02) improved postoperatively. In the grade three group, 1/7 (14.29%) patients experienced transient neuritis that resolved at 3 months without further treatment and 1/7 (14.29%) patients required revision surgery to an open midline splitting Haglund’s resection. Meanwhile no patients in either the grade one or grade two groups required reoperation, rehospitalization, or complications. 13/14 (93%) patients were very satisfied with their procedure and wound undergo it again. Conclusion: These early data suggest that patients with IAT, regardless of severity, improve after MIS ZO. Therefore, ZO may be a reasonable first line option for all patients presenting with IAT. In our small retrospective study, we were able to demonstrate significant improvement in pain and/or function following ZO in all grades of IAT tendinous pathology on preoperative MRI. This study may help guide surgeons when deciding between MIS ZO and other surgical options for IAT and Haglund’s deformity. Further, large prospective studies are warranted to further investigate outcomes and indications of MIS ZO in patients with IAT and Haglund’s deformit

Percutaneous vs Open Zadek Osteotomy for Treatment of Insertional Achilles Tendinopathy and Haglund’s Deformity: A Systematic Review

Background: Percutaneous Zadek osteotomy (ZO) has emerged as a surgical treatment of insertional Achilles tendinopathy (IAT) over the last decade. Existing literature is limited regarding the comparison of this approach with the more established, open ZO technique. This systematic review aims to evaluate and compare the current data on open vs percutaneous ZO approaches to help set evidence-based guidelines. Methods: A systematic literature search was performed using the keywords (Zadek osteotomy) OR (Keck and Kelly osteotomy) OR (dorsal closing wedge calcaneal osteotomy) OR (Haglund Deformity) OR (Haglund Syndrome) OR (Insertional Achilles Tendinopathy) and MeSH terms Osteotomy , Calcaneus , Syndrome , Insertional , Achilles tendon , and Tendinopathy . Our search included the following databases: PubMed, Embase, and the Cochrane Library. The PRISMA protocol and the Cochrane Handbook guidelines were followed. All studies included were published from 2009 to 2024 and included the use of open or percutaneous approaches of ZO for the treatment of IAT with at least a 12-month follow-up. The MINORS score criteria were used to evaluate the strength and quality of studies. Results: A total of 17 studies were reviewed, including 611 subjects and 625 ZO procedures. Of these procedures, 81 (11%) subjects had a percutaneous and 544 (89%) subjects had an open ZO. The mean follow-up time was 16.1 months for patients treated with percutaneous ZO and 36.1 months for patients treated with open ZO. Both open and percutaneous studies included in this review showed postoperative improvements in AOFAS, FFI, VISA-A, and VAS scores in patients with IAT. The reported complication rate was 5.8% among patients treated with percutaneous ZO and 10.2% among patients treated with open ZO. Conclusion: Percutaneous ZO is an emerging approach with substantially fewer documented cases compared with the open ZO. Both percutaneous and open ZO appear to be relatively effective treatments for insertional Achilles tendinopathy with Haglund’s deformity. The lower complication rates reported for percutaneous ZO is encouraging. Further investigation with more subjects undergoing percutaneous ZO is clearly needed

Severity of Achilles Tendinopathy on Preoperative MRI and Short-term Functional Outcomes After Minimally Invasive Zadek Osteotomy

Background: Limited literature is available to guide surgeons on which patients with insertional Achilles tendinopathy (IAT) may be the best candidates for minimally invasive dorsal closing wedge calcaneal Zadek osteotomy (MIS ZO). We hypothesized that the severity of IAT on preoperative magnetic resonance image (MRI) may correlate with post-operative functional outcomes and help guide patient selection for treatment with MIS ZO. Methods: Patients who underwent MIS ZO for IAT ± Haglund deformity were identified and retrospectively analyzed. IAT severity was graded on preoperative MRI. Patient Reported Outcome Measurement Information System (PROMIS) scores, complications, and revisions were recorded. Continuous data were compared by analysis of variance with Bonferroni post hoc analysis. Results: Seventeen patients treated with MIS ZO, with follow-up >6 months, and preoperative MRI met our inclusion criteria. PROMIS pain scores significantly improved in patients with IAT grades 1-3, with 5, 5, and 7 patients, respectively, in each subgroup. In this small series we only identified statistically significant improvements in PROMIS function ( P  = .031), and mobility ( P  = .009) scores were only observed in patients with grade 2 pathology. Sixteen of 17 patients (94.2%) were very satisfied with their procedure and would undergo it again. Conclusion: In this pilot study, we did not find preoperative MRI findings to correlate well with patient-reported outcome scores following MIS ZO. Level of Evidence: Level IV, case series

A review of research on e-marketplaces 1997-2008

Electronic marketplaces are an important research theme on the information systems landscape. In this paper we examine twelve years of research on electronic marketplaces in leading information systems journals. The research articles are classified according to five conceptual high level groupings: electronic markets theory; system perspective with a focus on the technology or functionality with the system; adoption and implementation issues; organisational implications; and broader e-commerce issues. The findings show an increase in electronic marketplace (e-marketplace) research over the twelve years. The analysis of the literature highlights two distinct issues that researchers in the information systems discipline need to address. The first is the lack of research on the fundamental questions on the nature of electronic markets and their efficiency. If information systems research does not address this question then it will not be seen as tackling critical issues by those outside of the discipline. The second is the relative lack of articles on the organisational implications of adopting and managing electronic marketplaces. These include, the organisational benefits, costs and risks of trading through e-marketplaces and strategies and methodologies for managing organisational participation. Both issues can be addressed by increasing the number of macro studies examining efficiencies in electronic markets