300 research outputs found

    Complications, Conversion, and Secondary Procedures Following Minimally Invasive Periacetabular Osteotomy: A Single-Surgeon Case Series

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    \ua9 2025 The AuthorsBackground: The introduction of minimally invasive periacetabular osteotomy (PAO) has reduced complications, allowing a broader range of patients to be considered for the procedure. This study aimed to identify patient-specific risk factors for poor outcomes. Methods: This retrospective case series (n = 513) used data from a local hip registration registry. Isolated PAOs with at least 1-year follow-up were included. Electronic records were reviewed to extract demographics and variables. The primary outcome was complication rate, with secondary outcomes including secondary procedures and conversion to total hip arthroplasty. Logistic regression was performed to correlate independent variables to outcomes, and Kaplan-Meier analysis assessed the survival of the native hip and cumulative complication risk. Results: Complication rate was 6.2%. Higher body mass index (BMI), smoking, T\uf6nnis grade 2, and increasing age were associated with higher odds of complications (P < .05). The nonunion rate was 4.3%; higher BMI and age linked to increased risk (P < .05). 10.9% of patients required a secondary procedure and cumulative risk for secondary procedures at 5 years was 11.4% and at 10 years was 17.2%. BMI correlated with the need for secondary procedures (P = .001). 3.7% (n = 19) required conversion to total hip arthroplasty with a mean time to conversion of 4.6 years \ub12.04. The 5- and 10-year survival rates were 96.3 and 92.7%, respectively. Conclusions: Minimally invasive PAO has acceptable rates of complication and conversion at mid-term follow-up. Age, BMI, smoking status, and T\uf6nnis grade 2 are associated with inferior outcomes. Knowledge of patient-specific risk factors can help in decision-making, expectation setting, and perioperative interventions

    From mesenchymal niches to engineered in vitro model systems: Exploring and exploiting biomechanical regulation of vertebrate hedgehog signalling

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    Tissue patterning is the result of complex interactions between transcriptional programs and various mechanical cues that modulate cell behaviour and drive morphogenesis. Vertebrate Hedgehog signalling plays key roles in embryogenesis and adult tissue homeostasis, and is central to skeletal development and the osteogenic differentiation of mesenchymal stem cells. The expression of several components of the Hedgehog signalling pathway have been reported to be mechanically regulated in mesodermal tissue patterning and osteogenic differentiation in response to external stimulation. Since a number of bone developmental defects and skeletal diseases, such as osteoporosis, are directly linked to aberrant Hedgehog signalling, a better knowledge of the regulation of Hedgehog signalling in the mechanosensitive bone marrow-residing mesenchymal stromal cells will present novel avenues for modelling these diseases and uncover novel opportunities for extracellular matrix-targeted therapies. In this review, we present a brief overview of the key molecular players involved in Hedgehog signalling and the basic concepts of mechanobiology, with a focus on bone development and regeneration. We also highlight the correlation between the activation of the Hedgehog signalling pathway in response to mechanical cues and osteogenesis in bone marrow-derived mesenchymal stromal cells. Finally, we propose different tissue engineering strategies to apply the expanding knowledge of 3D material-cell interactions in the modulation of Hedgehog signalling in vitro for fundamental and translational research applications

    Bioinspired Precision Engineering of Three‐Dimensional Epithelial Stem Cell Microniches

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    Maintenance of the epithelium relies on stem cells residing within specialized microenvironments, known as epithelial crypts. Two‐photon polymerization (2PP) is a valuable tool for fabricating 3D micro/nanostructures for stem cell niche engineering applications. Herein, biomimetic gelatin methacrylate‐based constructs, replicating the precise geometry of the limbal epithelial crypt structures (limbal stem cell “microniches”) as an exemplar epithelial niche, are fabricated using 2PP. Human limbal epithelial stem cells (hLESCs) are seeded within the microniches in xeno‐free conditions to investigate their ability to repopulate the crypts and the expression of various differentiation markers. Cell proliferation and a zonation in cell phenotype along the z‐axis are observed without the use of exogenous signaling molecules. Significant differences in cell phenotype between cells located at the base of the microniche and those situated towards the rim are observed, demonstrating that stem cell fate is strongly influenced by its location within a niche and the geometrical details of where it resides. This study provides insight into the influence of the niche’s spatial geometry on hLESCs and demonstrates a flexible approach for the fabrication of biomimetic crypt‐like structures in epithelial tissues. This has significant implications for regenerative medicine applications and can ultimately lead to implantable synthetic “niche‐based” treatments

    Designing topographically textured microparticles for induction and modulation of osteogenesis in mesenchymal stem cell engineering

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    Mesenchymal stem cells are the focus of intense research in bone development and regeneration. The potential of microparticles as modulating moieties of osteogenic response by utilizing their architectural features is demonstrated herein. Topographically textured microparticles of varying microscale features are produced by exploiting phase-separation of a readily soluble sacrificial component from polylactic acid. The influence of varying topographical features on primary human mesenchymal stem cell attachment, proliferation and markers of osteogenesis is investigated. In the absence of osteoinductive supplements, cells cultured on textured microparticles exhibit notably increased expression of osteogenic markers relative to conventional smooth microparticles. They also exhibit varying morphological, attachment and proliferation responses. Significantly altered gene expression and metabolic profiles are observed, with varying histological characteristics in vivo. This study highlights how tailoring topographical design offers cell-instructive 3D microenvironments which allow manipulation of stem cell fate by eliciting the desired downstream response without use of exogenous osteoinductive factors

    Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

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    BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

    A Two-stage Flow-based Intrusion Detection Model ForNext-generation Networks

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    The next-generation network provides state-of-the-art access-independent services over converged mobile and fixed networks. Security in the converged network environment is a major challenge. Traditional packet and protocol-based intrusion detection techniques cannot be used in next-generation networks due to slow throughput, low accuracy and their inability to inspect encrypted payload. An alternative solution for protection of next-generation networks is to use network flow records for detection of malicious activity in the network traffic. The network flow records are independent of access networks and user applications. In this paper, we propose a two-stage flow-based intrusion detection system for next-generation networks. The first stage uses an enhanced unsupervised one-class support vector machine which separates malicious flows from normal network traffic. The second stage uses a self-organizing map which automatically groups malicious flows into different alert clusters. We validated the proposed approach on two flow-based datasets and obtained promising results

    Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNα in patients with metastatic melanoma

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    The purpose of this study is to determine the toxicity and efficacy of temozolomide (TMZ) p.o. followed by subcutaneous (s.c.) low-dose interleukin-2 (IL2), granulocyte-monocyte colony stimulating factor (GM-CSF) and interferon-alpha 2b (IFN alpha) in patients with metastatic melanoma. A total of 74 evaluable patients received, in four separate cohorts, escalating doses of TMZ (150-250 mg m(-2)) for 5 days followed by s.c. IL2 (4 MIU m(-2)), GM-CSF (2.5 microg kg(-1)) and IFN alpha (5 MIU flat) for 12 days. A second identical treatment was scheduled on day 22 and cycles were repeated in stable or responding patients following evaluation. Data were analysed after a median follow-up of 20 months (12-30 months). The overall objective response rate was 31% (23 out of 74; confidence limits 20.8-42.9%) with 5% CR. Responses occurred in all disease sites including the central nervous system (CNS). Of the 36 patients with responding or stable disease, none developed CNS metastasis as the first or concurrent site of progressive disease. Median survival was 252 days (8.3 months), 1 year survival 41%. Thrombocytopenia was the primary toxicity of TMZ and was dose- and patient-dependent. Lymphocytopenia (grade 3-4 CTC) occurred in 48.5% (34 out of 70) fully monitored patients following TMZ and was present after immunotherapy in two patients. The main toxicity of combined immunotherapy was the flu-like syndrome (grade 3) and transient liver function disturbances (grade 2 in 20, grade 3 in 15 patients). TMZ p.o. followed by s.c. combined immunotherapy demonstrates efficacy in patients with stage IV melanoma and is associated with toxicity that is manageable on an outpatient basi

    Clarifying the role of three-dimensional transvaginal sonography in reproductive medicine: an evidenced-based appraisal

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    This overview describes and illustrates the clinical applications of three-dimensional transvaginal sonography in reproductive medicine. Its main applications include assessment of uterine anomalies, intrauterine pathology, tubal patency, polycystic ovaries, ovarian follicular monitoring and endometrial receptivity. It is also useful for detailed evaluation of failed and/or ectopic pregnancy. Three-dimensional color Doppler sonography provides enhanced depiction of uterine, endometrial, and ovarian vascularity
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