Hyaluronic acid treatment outcome on the post-extraction wound healing in patients with poorly controlled type 2 diabetes : a randomized controlled split-mouth study

Hyaluronic acid is widely used in the medical field. However, there is a lack of research about its effect on patients with certain risks, such as compromised wound healing commonly found in patients with poorly controlled type 2 diabetes. The aim of this study is to investigate the efficacy of hyaluronic acid on the post-extraction wound healing and pain in patients with poorly controlled type 2 diabetes. The randomized controlled split-mouth study was designed, which included 30 patients with poorly controlled type 2 diabetes with a bilaterally same teeth in the lower jaw for extraction. The sockets treated with 0.8% hyaluronic acid represented the study group, while the sockets where hyaluronic acid was not applied represented the control group. Wound closure rate (WCR), clinical scores in wound healing scale (WHS) and pain intensity in Visual analogue scale (VAS) were recorded. Patients were followed up on 5th, 10th, 15th, 20th, 25th day after tooth extraction. The results showed a higher WCR at the extraction site where hyaluronic acid was applied. Also, statistically significant difference was found (p< 0.001). In regards to WHS, the sockets treated with hyaluronic acid showed better healing, especially on day 10 (p=0.006) and day 15 (p=0.021). However, there were no statistically significant differences in VAS scores between groups. Hyaluronic acid placed in post-extraction socket in patients with poorly controlled diabetes may improve wound healing, especially in the first days after application

Labile plasma iron levels predict survival in patients with lower-risk Myelodysplastic syndromes

Red blood cell transfusions remain one of the cornerstones in supportive care of lower-risk patients with myelodysplastic syndromes. We hypothesized that patients develop oxidant mediated tissue injury through the formation of toxic iron species, caused either by red blood cell transfusions or by ineffective erythropoiesis. We analyzed serum samples from 100 lower-risk patients with myelodysplastic syndromes at six-month intervals for transferrin saturation, hepcidin-25, growth differentiation factor 15, soluble transferrin receptor, non-transferrin bound iron and labile plasma iron in order to evaluate temporal changes in iron metabolism and presence of potentially toxic iron species and their impact on survival. Hepcidin levels were low in 34 patients with ringed sideroblasts compared to 66 patients without. Increases of hepcidin and non-transferrin bound iron levels were visible early in follow-up of all transfusion dependent patient groups. Hepcidin levels significantly decreased over time in transfusion independent patients with ringed sideroblasts. Increased soluble transferrin receptor levels in transfusion-independent patients with ringed sideroblasts confirmed the presence of ineffective erythropoiesis and suppression of hepcidin production in these patients. Detectable labile plasma iron levels in combination with high transferrin saturation levels occurred almost exclusively in patients with ringed sideroblasts and all transfusion dependent patient groups. Detectable labile plasma iron levels in transfusion dependent patients without ringed sideroblasts were associated with decreased survival. IN CONCLUSION: toxic iron species occurred in all transfusion dependent patients and in transfusion independent patients with ringed sideroblasts. Labile plasma iron appeared to be a clinically relevant measure for potential iron toxicity and a prognostic factor for survival in transfusion dependent patients. This trial was registered at www.clinicaltrials.gov as #NCT00600860

Toxic iron species in lower-risk myelodysplastic syndrome patients : course of disease and effects on outcome

Item does not contain fulltex

Novel dynamic outcome indicators and clinical endpoints in myelodysplastic syndrome; the European LeukemiaNet MDS Registry and MDS-RIGHT project perspective

Available evidence suggests that in most patients with LR-MDS the risk of death is not related to disease progression but is mainly attributable to non-leukemic death. 2,17 In addition, a proportion of these patients have prolonged survival that precludes the design of clinical trials adopting OS as a primary endpoint. These challenges have resulted in potentially biased assessment of the effectiveness and appropriate use of the available interventions in this patient population. The EUMDS Registry has identified novel meaningful outcome indicators and clinical endpoints, and reliable measures of response to HCI (Figure 4). The results of our analysis indicate that RBCT density is strongly associated with a decreased OS, even at relatively low dose densities. In addition, we observed that an early decrease in platelet count is an independent adverse prognostic indicator in LR-MDS, and combining relative platelet drop and transfusion dependency allows early identification of patients at risk of rapid progression, and may guide early therapeutic interventions, including allogeneic hematopoietic stem cell transplantation or experimental interventions. Taken together, these results indicate that regular RBCT requirement, early platelet count kinetics, and restriction in HRQoL are early independent and meaningful outcome indicators, and reliable measures of effectiveness of therapeutic interventions, evaluated in this set of studies. These findings support the integration of RBCT requirement and HRQoL in the general core outcome sets and in response criteria in patients with LR-MDS, and have important implications for clinical practice and the design of clinical endpoints. Our results strongly support the adoption of freedom from transfusion as a meaningful clinical endpoint in patients with LR-MDS. Anemia is the main determinant of therapeutic intervention in patients with LR-MDS, and ESA are recommended as first-line treatment for patients with symptomatic anemia. 10 The observational studies within the EUMDS Registry showed that the response rate, as well as the capacity of these agents to delay the onset of a regular RBCT need, is most pronounced in RBCT-naïve patients. These results identified early initiation of treatment with ESA as a major treatment response indicator, and indicate that ESA should be recommended in LR-MDS patients with symptomatic anemia before starting regular RBCT. After the onset of RBCT dependency, patients with LR-MDS are prone to long-term accumulation of iron. 1,43 The EUMDS Registry studies provided evidence that elevated LPI levels are associated with reduced survival in RBCT dependent patients, whereas iron chelation therapy normalizes LPI levels. These findings suggest that NTBI and LPI may serve as early indicators of iron toxicity and a means to measure the effectiveness of iron chelation therapy in patients with LR-MDS. However, qualified NTBI and LPI are only currently available in specialized laboratories. 44 Large observational cohorts with detailed clinical and laboratory data, like the EUMDS cohort, are the ideal framework in which to identify well defined MDS subtypes that may benefit from novel targeted treatments. An example of such a subtype is MDS with loss of parts of chromosome 5, namely del5q; these patients have a relatively favorable outcome on lenalidomide treatment. In order to identify homogeneous subsets of patients within MDS, preliminary evidence has suggested that recently identified mutations in splicing factors may recognize distinct disease entities within myeloid neoplasms. 45 Splicing modulators are now in pre-clinical testing, and are very likely to lead to the introduction of effective drugs for specific groups of MDS patients. Luspatercept, a specific inhibitor of growth and differentiation factor-11, a member of the transforming growth factor β superfamily, induced substantial improvement of anemia, especially in patients with ring sideroblasts. 46 Characterization of individual cases by new genetic markers (one of the main objectives of the MDS-RIGHT project) will allow refined classification of patients into biological subgroups that are expected to respond differently to therapeutic interventions to guide discontinuation of those interventions that are less effective or less cost-effective. The main question is whether RCT data and retrospective cohort data in selected tertiary care centers are representative of the 'real world' data of the older patients with LR-MDS in the general population. A careful comparison of the 'real world' data and the RCT data will be needed in order to provide a clear answer to these questions. Meanwhile, the current analyses of data collected over 10 years in the EUMDS Registry provides relevant and important information which could help assess prognosis and response to standard interventions in this older patient group

Microanatomical study of replaced meniscus in the rabbit.

We investigated clinical and morphological characteristics of replaced menisci after the transplantation of deep frozen meniscal allografts. We replaced medial menisci (in 18 New Zealand white rabbits) by meniscal grafts obtained fro m other rabbits. These grafts were kept in a deep f reezer (3-5 weeks), thawed in sterile saline and transplanted. The menisci were removed and studied after 2 weeks (first group), 8 weeks (second group) and after 36 weeks (third gro u p ) . Menisci from non-operated, contralateral knees served as controls. The tissue of the menisci investigated was processed using several histological and histochemical methods and analyzed by light microscope. Transplanted meniscal allografts retained a normal gross appearance, healed f i rmly through fibrovascular tissue to the re c i p i e n t capsular tissue, and did not show macro s c o p i c pathological changes. At the histological evaluation, in the first group the collagen fibers were i r regularly oriented, with a low cellular population. In the second group, blood vessels were p resent, cellular repopulation and immature collagen fibers being observed. The third group had a more mature collagen tissue, with a significant cell repopulation. Deep-frozen meniscal allografts showed significant collagen remodeling with cellular and vascular ingrowth from the surro u n d i n g synovia. This suggests that used allografts function normally and protect underlying cartilage

Stem cells from the dental apical papilla in extracellular matrix hydrogels mitigate inflammation of microglial cells

After spinal cord injury (SCI) chronic inflammation hampers regeneration. Influencing the local microenvironment after SCI may provide a strategy to modulate inflammation and the immune response. The objectives of this work were to determine whether bone or spinal cord derived ECM hydrogels can deliver human mesenchymal stem cells from the apical papilla (SCAP) to reduce local inflammation and provide a regenerative microenvironment. Bone hydrogels (8 and 10 mg/ml, B8 and B10) and spinal cord hydrogels (8 mg/ml, S8) supplemented with fibrin possessed a gelation rate and a storage modulus compatible with spinal cord implantation. S8 and B8 impact on the expression of anti and pro-inflammatory cytokines (Arg1, Nos2, Tnf) in LPS treated microglial cells were assessed using solubilised and solid hydrogel forms. S8 significantly reduced the Nos2/Arg1 ratio and solubilised B8 significantly reduced Tnf and increased Arg1 whereas solid S8 and B8 did not impact inflammation in microglial cells. SCAP incorporation within ECM hydrogels did not impact upon SCAP immunoregulatory properties, with significant downregulation of Nos2/Arg1 ratio observed for all SCAP embedded hydrogels. Tnf expression was reduced with SCAP embedded in B8, reflecting the gene expression observed with the innate hydrogel. Thus, ECM hydrogels are suitable vehicles to deliver SCAP due to their physical properties, preservation of SCAP viability and immunomodulatory capacity

Experimental Dimensional Accuracy Analysis of Reformer Prototype Model Produced by FDM and SLA 3D Printing Technology

The subject of this paper is the evaluation of the dimensional accuracy of FDM and SLA 3D printing technologies in comparison with developed reformer polymer electrolyte membrane (PEM) fuel cell CAD model. 3D printing technologies allow a bottom-up approach to manufacturing, by depositing material in layers to final shape. Dimensional inaccuracy is still a problem in 3D printing technologies due to material shrinking and residual stress. Materials used in this research are PLA (Polylactic Acid) for FDM technology and the standard white resin material for SLA technology. Both materials are commonly used for 3D printing. PLA material is printed in three different height resolutions: 0.3 mm, 0.2 mm and 0.1 mm. White resin is printed in 0.1 mm height resolution. The aim of this paper is to show how layer height affects the dimensional accuracy of FDM models and to compare the dimensional accuracy of FDM and SLA printed reformer models with the same height resolution