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  • Womble Lillelund posted an update 1 day, 11 hours ago

    Osteonecrosis is one of the most disabling diseases affecting pediatric and adult populations. Local application of biomaterials is a promising therapeutic strategy for osteonecrosis. Currently, there is a lack of low-cost animal models of osteonecrosis for testing and developing biomaterials-driven therapeutics. To develop a rat model of ischemic osteonecrosis (IO), the distal femoral epiphysis was selected due to its size 7.7 folds larger than the proximal femoral epiphysis (p less then 0.0001). The feasibility of intraosseous drillings and the local application of biomaterials were determined. Four model biomaterials were successfully applied injectable hydrogel, microsphere, bone cement, and implant. The IO was induced by surgically cauterizing the blood vessels supplying the distal femoral epiphysis. Osteonecrosis of the whole epiphysis was achieved with a complete absence of blood flow and near 100% of apoptotic osteocytes. At eight weeks after IO, severe bone deformity and osteoarthritis developed in tstal femoral epiphysis of rats. The model is highly efficient in developing osteonecrosis with relatively low cost and it provides suitable skeletal size to apply various forms of biomaterials. More importantly, it mimicked the pathological features and progression of osteonecrosis in humans. The study is expected to have an important impact on the development and testing of innovative biological therapeutics for osteonecrosis.Blood compatible materials are required for the development of therapeutic and diagnostic blood contacting devices as blood-material interactions are a key factor dictating device functionality. In this work, we explored biofunctionalization of silk biomaterials with a recombinantly expressed domain V of the human basement membrane proteoglycan perlecan (rDV) towards the development of blood compatible surfaces. Perlecan and rDV are of interest in vascular device development as they uniquely support endothelial cell, while inhibiting smooth muscle cell and platelet interactions. rDV was covalently immobilized on silk biomaterials using plasma immersion ion implantation (PIII), a new method of immobilizing proteins on silk biomaterials that does not rely on modification of specific amino acids in the silk protein chain, and compared to physisorbed and carbodiimide immobilized rDV. Untreated and treated silk biomaterials were examined for interactions with blood components with varying degrees of complexity, invascular device development as they uniquely support endothelial cell, while inhibiting smooth muscle cell and platelet interactions. rDV was covalently immobilized on silk biomaterials using plasma immersion ion implantation (PIII), a new method of immobilizing proteins on silk biomaterials that does not rely on modification of specific amino acids in the silk protein chain. These biomimetic silk biomaterials are a promising platform toward development of silk-based blood-contacting devices for therapeutic, diagnostic, and research applications.

    Though hepatic resection (HR) is the standard local therapy for patients with colorectal cancer liver metastases (CRLMs), currently, radiofrequency ablation (RFA) may play an alternative role for elderly and vulnerable patients with various organ dysfunctions. This study aims to compare the prognosis of RFA and HR in treatment of CRLMs.

    A systematic search of PubMed, Embase, Cochrane Library and Web of Science up to October 1, 2020 was conducted for relevant studies that compared the prognosis of RFA with HR in the treatment of CRLMs. The primary outcomes were 30-day mortality, long-term recurrence, overall survival (OS) and disease-free survival (DFS). The secondary outcomes were various factors of OS, recurrence-free survival (RFS), survival, recurrence and complication.

    A total of 22 studies including 4385 CRLM patients were identified. There was no significant difference between RFA and HR in 30-day mortality, with a pooled OR of 0.88 (95% CI 0.34-2.29; P=0.80). CRLM patients undergoing RFA experienensity score matching studies should be performed to clarify the effectiveness of RFA and to determine target populations that benefit most from RFA in the future.

    Though the 30-day mortality of RFA was equal to HR, RFA showed a higher recurrence rate and poor long-term survival outcomes for CRLM patients. Tumor size, multiple tumors, age, primary node positive and metachronous metastasis were independent factors of survival. However, the results were limited because of the inequality baseline characteristics between the comparative groups. Randomized or propensity score matching studies should be performed to clarify the effectiveness of RFA and to determine target populations that benefit most from RFA in the future.Aortic stenosis was once considered a pure isolated valve obstacle challenging left ventricle driving force of contraction and flow generation. Left ventricular (LV) adaptation was merely interpreted as a uniform hypertrophic response to increased afterload. However, in these last 2 decades cardiac imaging research and some histopathology correlation studies brought insight towards the complex interaction between the vasculature, the valve and the myocardium. Verily, LV remodeling in this setting is a complex multidetermined process that goes further beyond myocardial hypertrophy. Ultrastructural changes involving both diffuse and replacement fibrosis of the myocardium take part and might explain the transition of clinical phenotypes with distinct prognosis, from compensated hypertrophy to LV maladaptive dysfunction and heart failure. Presently, the combined appropriate use of echocardiography and cardiac magnetic resonance may better assess the global LV afterload, hypertrophy and geometric remodeling, global and regional LV function, beyond ejection fraction, and structural changes that include the fibrotic burden of the myocardium. see more As a whole these may not only better stratify individual risk of disease progression but also identify patients benefiting from earlier valve intervention. In this paper, we review the maladaptive response of the LV to chronic pressure overload, describing the different signaling pathways and mechanisms that underly both hypertrophy and remodeling. Histomorphology changes in this setting are described and we try to make sense of the use of new imaging tools for LV characterization.

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