Management of syndesmotic injuries:What is the evidence?

Ankle fractures are accompanied by a syndesmotic injury in about 10% of operatively treated ankle fractures. Usually, the total rupture of the syndesmotic ligaments with an external rotation force is associated with a Weber type B or C fracture or a Maisonneuve fracture. The clinical assessment should consist of a comprehensive history including mechanism of injury followed by a specific physical examination. Radiographs, and if in doubt magnetic resonance imaging, are needed to ascertain the syndesmotic injury. In the case of operative treatment the method of fixation, the height and number of screws and the need for hardware removal are still under discussion. Furthermore, intraoperative assessment of the accuracy of reduction of the fibula in the incisura using fluoroscopy is difficult. A possible solution might be the assessment with intraoperative three-dimensional imaging. The aim of this article is to provide a current concepts review of the clinical presentation, diagnosis and treatment of syndesmotic injuries.

Surface Coating of NiTi Shape Memory Alloys with Calcium Phosphates by Dip-coating or Plasma-spraying-biological Characterization Examined by in vitro Testing Methods

The influence of different surface coatings of NiTi shape memory allays was examined using in vitro testing methods. Plates of superelastic nickel-titanium shape memory allay （ NiTi ） were coated with calcium phosphates （ hydroxyapatite ） by high-temperature plasma-spraying or by dip-coating. The biocompatibility was tested in vitro by cultivation of isolated human granulocytes and whole blood cells. As substrates, pure NiTi, plasma-spray-coated NiTi and dip-coated NiTi were used. Isolated granulocytes showed an increased adhesion to both calcium phosphate-coated NiTi samples. Compared to non-coated NiTi or dip-coated NiTi, the number of dead granulocytes adherent to plasma-sprayed surfaces was significantly increased （ p 〈 0.01 ）. Whether the d/f- ferences in apoptosis of granulocytes on dip-coated vs plasma-sprayed coatings observed are due to differences in material surface morphologies has to be analyzed in further studies. Because of the cellular interactions with the coating layers, h is likely that the results obtained are not caused by the underlying NiTi but due to the coating itself.

Effects of immune cells on mesenchymal stem cells during fracture healing

In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune cells.This osteoimmune system is based on cooperatively acting bone and immune cells,cohabitating within the bone marrow.They are highly interdependent,a fact that is confounded by shared progenitors,mediators,and signaling pathways.Successful fracture healing requires the participation of all the precursors,immune and bone cells found in the osteoimmune system.Recent evidence demonstrated that changes of the immune cell composition and function may negatively influence bone healing.In this review,first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more closely.The separate paragraphs focus on the specific cell types,starting with the cells of the innate immune response followed by cells of the adaptive immune response,and the complement system as mediator between them.Finally,a brief overview on the challenges of preclinical testing of immunebased therapeutic strategies to support fracture healing will be given.

Diagnostic Power of Diffusion-weighted Magnetic Resonance Imaging for the Presence of Lymph Node Metastasis:A Meta-analysis

Present work was designed to quantitatively evaluate the performance of diffusion-weighted magnetic resonance imaging（DWI） in the diagnosis of the presence of metastasis in lymph nodes（LNs）. Eligible studies were identified from systematical Pub Med and EMBASE searches. Data were extracted. Meta-analyses were performed to generate pooled sensitivity and specificity on the basis of per-node, per-lesion and per-patient, respectively. Fourteen publications（2458 LNs, 404 lesions and 334 patients） were eligible. Per-node basis demonstrated the pooled sensitivity and specificity was 0.82（P〈0.0001） and 0.90（P〈0.0001）, respectively. Per-lesion basis illustrated the pooled sensitivity and specificity was 0.73（P=0.0036） and 0.85（P〈0.0001）, respectively. Per-patient basis indicated the pooled sensitivity and specificity was 0.67（P=0.0909） and 0.86（P〈0.0001）, respectively. In conclusion, DWI has rather a negative predictive value for the diagnosis of LN metastasis presence. The difference of the mean apparent diffusion coefficients between benign and malignant LNs is not yet stable. Therefore, the DWI technique has to be further improved.

Influence of immobilization and sensory re-education on the sensory recovery after reconstruction of digital nerves with direct suture or muscle-in-vein conduits

The influence of duration of immobilization and postoperative sensory re-education on the final outcome after reconstruction of digital nerves with direct suture or muscle-in-vein conduits was investigated. The final sensory outcome of 35 patients with 41 digital nerve injuries, who either underwent a direct suture（DS） or a nerve reconstruction with muscle-in-vein conduits（MVC）, was assessed the earliest 12 months postoperatively using static and moving two-point discrimination as well as Semmes-Weinstein monofilaments. There was no significant difference in sensory recovery in cases with an immobilization of 3–7 days versus 10 days in the DS or MVC group. Moreover, no statistically significant difference in sensory recovery was found in cases receiving postoperative sensory re-education versus those not receiving in the DS or MVC group. An early mobilization does not seem to have a negative impact on the final outcome after digital nerve reconstruction. The effect of sensory re-education after digital nerve reconstruction should be reconsidered.

Growth hormone abolishes the negative effects of everolimus on intestinal wound healing

AIM: To investigate whether the simultaneous treatment with human growth hormone(h GH) abolishes the negative effects of everolimus on anastomotic healing.METHODS: Forty-eight male Sprague-Dawley-rats were randomized to three groups of 16 animals each(Ⅰ: vehicle; Ⅱ: everolimus 3 mg/kg po; Ⅲ: everolimus 3 mg/kg po + h GH 2.5 mg/kg sc). Animals were pretreated with h GH and/or everolimus daily for seven days. Then a standard anastomosis was created in the descending colon and treatment was continued for another seven days. The anastomosis was resected in toto and the bursting pressure was assessed as a mechanical parameter of intestinal healing. Moreover, biochemical(Hydroxyproline, PCNA, MPO, MMP-2 and MMP-9) and histological(cell density, angiogenesis, amount of granulation tissue) parameters of intestinal healing were assessed.RESULTS: Anastomotic bursting pressure was significantly reduced by everolimus and a simultaneous treatment with h GH resulted in considerably higher values(Ⅰ: 134 ± 19 mm Hg, Ⅱ: 85 ± 25 mm Hg, Ⅲ: 114 ± 25 mm Hg; P < 0.05,Ⅰvs Ⅱ; P = 0.09,Ⅰvs Ⅲ and Ⅱ vs Ⅲ) Hydroxyproline concentration was significantly increased by h GH compared to everolimus alone(Ⅰ: 14.9 ± 2.5 μg/mg, Ⅱ: 8.9 ± 3.6 μg/mg, Ⅲ: 11.9 ± 2.8 μg/mg; P < 0.05,?Ⅰvs Ⅱ/Ⅲ and Ⅱ vs Ⅲ). The number of MPO-positive cells was reduced significantly by h GHcompared to everolimus alone(Ⅰ: 10 ± 1 n/mm^2, Ⅱ: 15 ± 3 n/mm^2, Ⅲ: 9 ± 2 n/mm^2; P < 0.05,Ⅰvs Ⅱ and Ⅱ vs Ⅲ), while the number of PCNA-positive cells were increased by h GH(Ⅰ: 28 ± 3 /mm^2, Ⅱ: 12 ± 3 /mm^2, Ⅲ: 26 ± 12 /mm^2; P < 0.05,?Ⅰ?vs Ⅱ and Ⅱ vs Ⅲ). Corresponding to these biochemical findings, HEhistology revealed significantly increased amount of granulation tissue in h GH-treated animals.CONCLUSION: Inhibition of intestinal wound healing by everolimus is partially neutralized by simultaeous treatment with h GH. Both inflammation as well as collagen deposition is influenced by h GH.

Improved Osteointegration of Ti-6Al-4V-implants of Different Surface Texture by the Use of Bone Morphogenetic Protein-3 (BMP-3)

Half of altogether 60 cylindrical implant devices made of titanium-aluminum-vanadium alloy （ Ti-6Al-4V） were plusna-sprayed with a hydroxyapatite-couting and the other half had a corundum blasted porous surface. 15 implants of each group of the titanium test buplants were coated with 230 μg porcine, high-purified BMP- 3-precipitute per implant. In each case a BMP- 3-couted and an uncoated control-device were implanted into the femoral part of the putellofemoral joint of the right and left leg of 30 adult giant rabbits. Histomorphological and histomorphometrical we found in both groups with BMP- 3-coated test devices an improved osteointegrution. Stutistical evaluation using the t-test for matched samples showed 5 weeks after surgery a significant higher volume of tony formed bone of the BMP- 3-coated corundum- blasted or hydroxyapathe- coated Ti- 6Al- 4 V test devices compared to the non-couted controls of the same t）pe （p 〈 0.01, t-test for matched samples）. In both implant groups with BMP-couting a synergetic effect was verifiable although the bone ongrowth in the hydroxyaputite coated implants was more extensive than in the corundum blasted implants. Light microscopy demonstrated osteointegrution without connective tissue membrane around the surface of the implants. Our results indicate that composite metal implants,as used in endoprosthetics and implantology , are suitable carriers for BMP- 3 and im proved fixation of the implants can be achieved. The hydroxyapatite surface is superior to the corundum-blasted surface with regards to the observed parameters because of its pronounced bioactivity and its osteoconductive characteristics.

Comparison of short- with long-term regeneration results after digital nerve reconstruction with musclein-vein conduits

Muscle-in-vein conduits are used alternatively to nerve grafts for bridging nerve defects. The purpose of this study was to examine short- and long-term regeneration results after digital nerve reconstruction with muscle-in-vein conduits. Static and moving two-point discriminations and Semmes-Weinstein Monofilaments were used to evaluate sensory recovery 6–12 months and 14–35 months after repair of digital nerves with muscle-in-vein in 7 cases. Both follow-ups were performed after clinical signs of progressing regeneration disappeared. In 4 of 7 cases, a further recovery of both two-point discriminations and in another case of only the static two-point discrimination of 1–3 mm could be found between the short-term and long-term follow-up examination. Moreover, a late recovery of both two-point discriminations was demonstrated in another case. Four of 7 cases showed a sensory improvement by one Semmes-Weinstein Monofilaments. This pilot study suggests that sensory recovery still takes place even when clinical signs of progressing regeneration disappear.

Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss

The clinical role and underlying mechanisms of valproic acid(VPA)on bone homeostasis remain controversial.Herein,we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density(BMD)in both patients and mice.This effect was attributed to VPA-induced elevation in osteoclast formation and activity.Through RNA-sequencing,we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro,and further,a marked upregulation of mature miR-6359(miR-6359)in vivo was demonstrated using quantitative real-time PCR(qRT-PCR)and miR-6359 fluorescent in situ hybridization(miR-6359-FISH).Specifically,the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils,T lymphocytes,monocytes and bone marrow-derived mesenchymal stem cells(BMSCs)following VPA stimulation,which influenced osteoclast differentiation and bone-resorptive activity.Additionally,VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species(ROS)production by silencing the SIRT3 protein expression,followed by activation of the MAPK signaling pathway,which enhanced osteoclast formation and activity,thereby accelerating bone loss.Currently,there are no medications that can effectively treat VPA-induced bone loss.Therefore,we constructed engineered small extracellular vesicles(E-sEVs)targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif(CGGGAGC)in the 3’-end of the anti-miR-6359 sequence.We confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss,but not on ovariectomy(OVX)and glucocorticoid-induced osteoporotic models,deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.

Immunomodulatory Nanosystems:Advanced Delivery Tools for Treating Chronic Wounds

The increasingly aging society led to a rise in the prevalence of chronic wounds(CWs),posing a significant burden to public health on a global scale.One of the key features of CWs is the presence of a maladjusted immune microenvironment characterized by persistent and excessive(hyper)inflammation.A variety of immunomodulatory therapies have been proposed to address this condition.Yet,to date,current delivery systems for immunomodulatory therapy remain inadequate and lack efficiency.This highlights the need for new therapeutic delivery systems,such as nanosystems,to manage the pathological inflammatory imbalance and,ultimately,improve the treatment outcomes of CWs.While a plethora of immunomodulatory nanosystems modifying the immune microenvironment of CWs have shown promising therapeutic effects,the literature on the intersection of immunomodulatory nanosystems and CWs remains relatively scarce.Therefore,this review aims to provide a comprehensive overview of the pathogenesis and characteristics of the immune microenvironment in CWs,discuss important advancements in our understanding of CW healing,and delineate the versatility and applicability of immunomodulatory nanosystems-based therapies in the therapeutic management of CWs.In addition,we herein also shed light on the main challenges and future perspectives in this rapidly evolving research field.

Open wedge re-correction high tibial osteotomy in an elderly patient with a varus angulated non-united dome-shaped high tibial osteotomy

The high tibial osteotomy(HTO)is a wellestablished and commonly used treatment for younger and active patients with a medial unicompartmental osteoarthritis of the knee and varus malalignment.The aim of this technique is to shift the load to a functional lateral compartment in order to delay total knee arthroplasty.The dome-shaped HTO was introduced by Blaimont et al.(1975)and later popularized by Maquet(1980).Out of 118 cases,96 cases of overcorrection,13 cases of undercorrection,and 9 cases

Current understanding of thermo(dys)regulation in severe burn injury and the pathophysiological influence of hypermetabolism,adrenergic stress and hypothalamic regulation-a systematic review

Background:In this systematic review,we summarize the aetiology as well as the current knowl-edge regarding thermo(dys)regulation and hypothermia after severe burn trauma and aim to present key concepts of pathophysiology and treatment options.Severe burn injuries with>20%total body surface area(TBSA)affected commonly leave the patient requiring several surgical procedures,prolonged hospital stays and cause substantial changes to body composition and metabolism in the acute and long-term phase.Particularly in severely burned patients,the loss of intact skin and the dysregulation of peripheral and central thermoregulatory processes may lead to substantial complications.Methods:A systematic and protocol-based search for suitable publications was conducted fol-lowing the PRISMA guidelines.Articles were screened and included if deemed eligible.This encompasses animal-based in vivo studies as well as clinical studies examining the control-loops of thermoregulation and metabolic stability within burn patients Results:Both experimental animal studies and clinical studies examining thermoregulation and metabolic functions within burn patients have produced a general understanding of core concepts which are,nonetheless,lacking in detail.We describe the wide range of pathophysiological alterations observed after severe burn trauma and highlight the association between thermoregulation and hypermetabolism as well as the interactions between nearly all organ systems.Lastly,the current clinical standards of mitigating the negative effects of thermodysregulation and hypothermia are summarized,as a comprehensive understanding and implementation of the key concepts is critical for patient survival and long-term well-being.Conclusions:The available in vivo animal models have provided many insights into the interwoven pathophysiology of severe burn injury,especially concerning thermoregulation.We offer an outlook on concepts of altered central thermoregulation from non-burn research as potential areas of future research interest and aim to provide an overview of the clinical implications of temperature management in burn patients.

Tissue conditioning-strategies to improve perfusion and reduce ischemia-reperfusion injury

Ischemia as well as ischemia-reperfusion injury (IRI) can cause serious tissue damage and therefore is a feared complication in reconstructive surgery. This is the reason why researchers around the world invest their efforts to improve tissue viability after ischemic events. Tissue conditioning offers a broad scope of different techniques which can be applied pre-, peri- or postoperatively to adapt the affected tissue to the subsequent stress during and after ischemia to prevent or minimize IRI. The different ways of tissue conditioning in flap surgery include surgical delay, ischemic conditioning, remote ischemic conditioning as well as thermic preconditioning and other techniques, using growth factors, pharmaceutical agents, extracorporeal shock waves as well as stemm cells. Therefore, we want to shed some light on the effects of ischemia and ischemia-reperfusion injury and further illustrate the different strategies of tissue conditioning with special concern to flap surgery but also regarding wound healing in general.

失血性休克与骨折愈合的研究进展

创伤后失血性休克常常与骨折同时发生,由于失血性休克可导致全身性系统改变,而骨折的愈合也是一个需要全身众多因素共同调控的综合过程。因此在失血性休克后骨折的研究中,除了对于骨折本身的治疗,其对于骨折愈合的影响也同样应受到重视。目前失血后导致的骨折不良愈合机制仍存有空白和争议,本文针对这个容易被临床忽视的角度,全面综述相关临床和基础研究,旨在为临床面对失血性休克后骨折不良愈合患者提供参考,也为进一步研究其内在机制启发新的研究思路。

Osteolectin+stromal cells:Mechanical stimulation improves bone regeneration and supports bacterial clearance after fracture

In a study recently published in Nature,Shen and colleagues characterized a peri-arteriolar niche in the bone marrow with highly proliferative,short-lived,leptin receptor-and osteolectin(Oln)positive stromal cells,which improved bone regeneration and supported bacterial clearance after fracture.By proving that maintenance of these cells critically required mechanical stimulation,which in turn was affected by age,1 the authors identified possible therapeutic targets for bone healing and regeneration.

State of the art in enzymatic debridement

Surgical treatment of deep partial thickness to full thickness burn wounds by knife has been the undisputed standard of care and was one key point in surgical burn medicine for decades. Recently, it gets more and more challenged by Bromelain-based enzymatic burn wound debridement (ED) as technique for non-surgical, selective eschar removal. Although the literature on ED is increasing constantly it cannot comprise the rapid progress that is made in clinical application of ED. To outline the current state of art in ED, recent literature as well as clinical experience is summarized and the main steps in clinical application including indications, wound preparation, application of the enzyme, wound bed assessment and further treatment after ED are discussed. Initial indications and limitations in application of ED could be gradually extended to increase versatility of ED as tool in burn surgery. Several randomized controlled trials compared ED to standard of care (SOC). They could show significant shorter time to complete burn wound debridement and wound closure, reduced need for surgery, reduced blood loss, reduced area of burns that needed surgical excision and need for autograft as well as an improved scar quality. Further research is necessary to justify an extensive use of ED as tool for burn eschar removal. Especially a robust comparison to surgical burn wound excision by knife as SOC is required to facilitate evidence-based burn surgery.