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Osteoarthritis, a major cause of disability in developed countries does not have effective treatment. Activation of TLR4 and innate immune response factors contribute to osteoarthritis progressive cartilage degradation. There are no clinically available TLR4 inhibitors. Interestingly, the antidepressant amitriptyline could block this receptor. Thus, we evaluated amitriptyline anti-TLR4 effects on human osteoarthritis chondrocytes in order to repurpose it as an inhibitor of innate immune response in joint inflammatory pathologies.Using in silico docking analysis, RT-PCR, siRNA, elisa, proteomics and clinical data mining of drug consumption, we explored the clinical relevance of amitriptyline blockade of TLR4-mediated innate immune responses in human osteoarthritis chondrocytes.Amitriptyline bound TLR4 but not IL-1 receptor. Interestingly, amitriptyline binding to TLR4 inhibited TLR4- and IL-1 receptor-mediated innate immune responses in human osteoarthritis chondrocytes, synoviocytes and osteoblasts cells. Amitriptyline reduced basal innate immune responses and promoted anabolic effects in human osteoarthritis chondrocytes. Supporting its anti-innate immune response effects, amitriptyline down-regulated basal and induced expression of NLRP3, an inflammasome member from IL-1 receptor signalling linked to osteoarthritis and gout pathologies. Accordingly, mining of dissociated and aggregated drug consumption data from 107,172 elderly patients (65 years) revealed that amitriptyline consumption was significantly associated with lower colchicine consumption associated with inflammatory gout flare treatment.Amitriptyline blocks TLR4-, IL-1 receptor and NLRP3-dependent innate immune responses. This together with clinical data amitriptyline could be repurposed for systemic or local innate immune response management in diverse joint inflammatory pathologies.

Introduction: Fracture-related infections (FRIs) are a devastating complication. FRIs are challenging and should be addressed with a multidisciplinary approach. An FRI should be addressed surgically by non-viable bone debridement, local antibiotic deposition, minimization of dead space and fracture stabilization. Antibiotic-laden PMMA-covered nails are a viable option to face these complications. To demonstrate the safety and utility of commercially available antibiotic-laden PMMA-covered nails, we performed a review of the cases operated in our institution and a cost analysis to compare the cost of a commercial nail to other available alternatives.Material and methods: We designed a retrospective study of consecutive cases to demonstrate the safety and efficacy of antibiotic-laden PMMA-covered commercial nails and designed a cost analysis of commercial coated nails compared to other custom-made alternatives.Results: We treated seven tibias and three femurs. Nine patients fully fit the criteria for FRI. There was one case of reintervention because of persistent drainage. All fractures healed, and in the first year post-intervention, there were no signs or symptoms of infection. There were no complications related to the commercially available nail that was used. There is a small increase in the direct quantifiable cost in commercially available nails, but non-quantifiable cost should be assessed individually.Conclusions: Commercially available antibiotic-laden PMMA-covered nails are a safe and useful treatment option for complicated cases of lower limb long bone reconstruction. The low complication rate and the straightforward technique compensate for the direct cost increase in most situations.

Background Proximal humeral fractures are common and a major concern in public health resources utilization. There is an increase in the use of reverse total shoulder arthroplasty (RTSA) as an option for complex fractures in the elderly. The complexity of the technique in RTSA is increased because of the fracture. To find an advantage of locking stems in RTSA for the treatment of proximal humeral fractures, we designed a comparative study between fracture-dedicated locking stems vs. cemented stems. Materials and methods We retrospectively studied 58 patients treated with an RTSA after a fracture. We compared how the implant design and the tuberosity consolidation affects patient outcome through measuring range of motion and the Constant score. Results The groups were similar in age, sex, time to surgery, and Constant score in the uninjured side. Patients treated with a dedicated locking noncemented stem performed better, with an increased Constant score (P > .05) and reached more mobility with no statistical significance. We found that 13 of the 24 fractures (54%) treated with a cemented stem consolidated, and 26 of 34 tuberosities (76%) healed in the noncemented locked stems. Patients with tuberosity consolidation acquired better range of motion and Constant scores (P Conclusions A dedicated stem improves tuberosity healing and increases outcomes seen in Constant scores. Tuberosity consolidation is a main goal when treating proximal humeral fractures with RTSA.

Screw insertion to bones is a fundamental skill in orthopedic, spine and cranio-maxillofacial surgery. Applying the correct tightening torque is critical when compressing and fixating bone fragments. Overtightening yields in plastic deformation of the bone and destruction of the screw-bone interface, damaging the construct's stability. The surgeon is required to achieve sufficient hold and compression without stripping the bone. Several studies have investigated these skills, demonstrating much potential to enhance the future surgeons' capabilities. This study presents a novel training module, combining direct tightening followed by deliberate striping with immediate feedback suggested to enhance the surgeon's tactile perception and improve skill.A prospective single-blinded cohort study was run. Twenty surgeons from various disciplines, excluding orthopedic and maxillo-facial surgeons, were trained using an orthopedic screws insertion model, comprised of synthetic bones. Training sessions considered inserting 40 screws into normal and osteoporotic bone models, experiencing deliberate stripping of the screws and feedback for their performance in three different sessions.Success rate increased between sessions - by 24% to 48% in normal bone, and by 37% to 52% in osteoporotic bone. Stripping rate decreased between sessions - by 37.5% to 18.5% in normal bone, and by 29% to 14% in osteoporotic bone. Average ratio between tightening torque and maximum possible torque before bone stripping improved gradually and consistently from 67.3% to 81.6% in normal bone (p 0.001), and slightly from 76.4% to 77.5% in osteoporotic bone (p = 0.026).Immediate feedback with deliberate stripping and external feedback using a digital torque measuring screwdriver may improve cortical screw insertion technique in the surgeons' community.

Interfragmentary compression, a major principle of fracture treatment, is clinically not quantified and might be lost quickly even without functional loads. We designed an experimental study hypothesizing that (1) compression can be controlled using either lag screw or compression plate, and expecting similar initial compression, (2) loss of interfragmentary compression through relaxation within one hour is reduced with neutralization locking plate next to lag screw compared to compression plate. Twelve ovine femora (N=6) and humeri (N=6) were assigned into groups: Group 1 received a 45° oblique osteotomy at mid-diaphysis and was fixated using a 3.5 mm interfragmentary lag screw and locking compression plate (3.5 mm LCP, DePuy Synthes) as neutralization plate. Group 2 received a transverse osteotomy and was fixated with dynamic compression using compression plate (LCP). Interfragmentary pressure and relative bone fragment displacements were recorded over one hour. Median loss of compression over one hour time (relaxation) were 0.52% in Group 1, and 0.17% in Group 2 (p>0.05). Median rotational displacements amounted to 0.46° for Group 1, and 0.31° for Group 2, and axial displacement to a median of −20 μm in Group 1 and 25 μm in Group 2. Ovine bone interfragmentary stress relaxation maintains compression over the first hour for lag screw with neutralization plate for an oblique fracture line or compression plate for a transverse fracture line. Measured compression forces around 100 N could be overcome by physiological tension loading in bending or torsion, necessitating for instance tension band plating, additional lag screws or absolutive stability.

Glycosylation of Apo CIII modulates its function in triglyceride metabolism, and some variants are associated with a protective or pro-atherogenic lipid profile. These associations have been studied in whole plasma Apo CIII proteoforms, but the proportion of Apo CIII proteoforms in individual lipoprotein fractions has been rarely evaluated. In the present study, we aim to measure the relative content of Apo CIII proteoforms in each lipoprotein fraction (VLDL, IDL, LDL and HDL) in a group of healthy subjects as a potential biomarker for triglyceride metabolism, cardiovascular risk and diabetes. Lipoprotein fractions were separated by differential ultracentrifugation of plasma samples. The relative concentrations of seven Apo CIII variants were measured by mass spectrometric immunoassay, and the complete lipoprotein profile was determined by NMR. The results showed high interindividual variability in the distribution of Apo CIII proteoforms across the study population but a uniform proportion in all lipoprotein fractions. Two Apo CIII variants, Apo CIII0band Apo CIII1d, were negatively correlated with plasma and VLDL triglycerides regardless of VLDL size and were associated with increased LDL size when transported in LDL particles. Apo CIII0balso showed a negative correlation with lipoprotein-insulin resistance score. Therefore, Apo CIII variants can be reliably measured in lipoprotein fractions, and our results suggest that Apo CIII0band Apo CIII1dhave a protective role in triglyceride metabolism and insulin resistance in healthy individuals.

Accurate prognostic tools are crucial to assess the risk/benefit ratio of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with myelofibrosis (MF). We aimed to evaluate the performance of the Myelofibrosis Transplant Scoring System (MTSS) and identify risk factors for survival in a multicenter series of 197 patients with MF undergoing allo-HCT. After a median follow-up of 3.1 years, 47% of patients had died, and the estimated 5 year survival rate was 51%. Projected 5-year risk of nonrelapse mortality and relapse incidence was 30% and 20%, respectively. Factors independently associated with increased mortality were a hematopoietic cell transplantation-specific comorbidity index (HCT-CI) 3 and receiving a graft from an HLA-mismatched unrelated donor or cord blood, whereas post-transplant cyclophosphamide (PT-Cy) was associated with improved survival. Donor type was the only parameter included in the MTSS model with independent prognostic value for survival. According to the MTSS, 3-year survival was 62%, 66%, 37%, and 17% for low-, intermediate-, high-, and very high-risk groups, respectively. By pooling together the lowand intermediate-risk groups, as well as the highand very high-risk groups, we pinpointed 2 categories: standard risk and high risk (25% of the series). Three-year survival was 62% in standard-risk and 25% in high-risk categories (P < .001). We derived a risk score based on the 3 independent risk factors for survival in our series (donor type, HCT-CI, and PT-Cy). The corresponding 5-year survival for the low-, intermediate-, and high-risk categories was 79%, 55%, and 32%, respectively (P < .001). In conclusion, the MTSS model failed to clearly delineate 4 prognostic groups in our series but may still be useful to identify a subset of patients with poor outcome. We provide a simple prognostic scoring system for risk/benefit considerations before transplantation in patients with MF. (C) 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

A retrospective descriptive study is conducted at the San Juan de Dios Hospital, San Jose, Costa Rica, during the period from February 2016 to March 2017, with a total of 37 patients from which a combined screening during the first trimester of pregnancy was conducted, evaluating maternal age, biochemical and sonographic methods that together can predict the risk of fetal chromosomal alterations during pregnancy. The purpose of using combined screening as a noninvasive method is to identify high risk gestations and to minimize the number of invasive procedures to detect the highest number of cases. Four patients with higher risk of aneuploidy during pregnancy were identified through this screening.

Glycosylation of ApoC-III modulates its function in TG metabolism, with some variants being associated with a more atherogenic lipid profile. These associations have been studied in whole plasma but rarely in individual lipoprotein fractions. In this study, we aimed to measure the relative content of ApoC-III glycoforms in each lipoprotein fraction as a potential biomarker for TG metabolism and cardiovascular risk. Lipoprotein fractions were separated by differential ultracentrifugation of plasma samples from healthy subjects. Relative concentrations of seven ApoC-III variants were measured by MSIA. ApoC-III1, ApoC-III0b and ApoC-III2 were the most abundant glycoforms. There was high interindividual variability in the distribution of glycoforms across the study population but a uniform proportion in all lipoprotein fractions of each given subject. Two ApoC-III variants, ApoC-III0b and ApoC-III1d, negatively correlated with plasma and VLDL triglycerides irrespectively of VLDL size and were associated with increased LDL size when transported in LDL particles. ApoC-III0b also showed a negative correlation with lipoprotein-insulin resistance score. We have been able to measure seven ApoC-III glycoforms in each lipoprotein fraction, setting the basis for future studies exploring their role on cardiovascular risk. Some glycoforms suggest a less proatherogenic role on TG and lipoprotein metabolism. Significance Apo CIII has an important role on plasma TG metabolism through different mechanisms and it is also involved in type 1 and type 2 Diabetes Mellitus. Different glycosylated forms of Apo CIII exist and they show different roles. For this reason, this protein has gained interest in the las years and the relationship between ApoC-III glycoforms and lipids, lipoproteins and metabolic disorders has been increasingly studied in the last years. Apo CIII glycoforms have been previously analysed in plasma, and the function of the main four glycoforms has been assessed in a variety of cohorts; but in the present study, ApoC-III glycoforms are measured in each lipoprotein fraction, which may be of clinical interest.

Objective: Thyroid storm is a rare life-threatening medical emergency. It is associated with high mortality (10 to 30%). Though there may be mild derangements in liver function tests (LFTs), acute liver failure (ALF) is infrequently reported and its pathophysiology is poorly understood. We hereby report a case of ALF in a patient with thyroid storm.Methods: A 41-year-old female with history of Graves disease (non-compliant with treatment) complicated by multiple episodes of thyroid storm and atrial fibrillation (Afib) presented with exertional dyspnea and productive cough. She was found to be in Afib with rapid ventricular rate and new-onset cardiomyopathy (left ventricular ejection fraction of

Objectives: Absolute stability for primary fracture healing requires interfragmentary compression. In daily practice, compression pressure distribution or force are not measured [ref:1]. Brink et al. 2013 showed that compressive forces were not sufficiently achieved in transverse olecranon[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2019)

Despite the substantial clinical benefits of antiretroviral therapy (ART), complete eradication of HIV has not been possible. The gastrointestinal tract and associated lymphoid tissues may play an important role in the pathogenesis of HIV infection. The integrin α4β7 facilitates homing of T lymphocytes to the gut by binding to the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed on venules in gut-associated lymphoid tissue. CD4+ T cells with increased expression of α4β7 are susceptible to HIV infection and may be key players in subsequent virus dissemination. Data from nonhuman primate models infected with simian immunodeficiency virus (SIV) have suggested that blockade of the α4β7/MAdCAM-1 interaction may be effective at preventing SIV infection and may have beneficial effects in animals with established viral infection. To explore whether these findings could be reproduced in HIV-infected individuals after interruption of ART, we conducted an open-label phase 1 clinical trial of vedolizumab, a monoclonal antibody against α4β7 integrin. Vedolizumab infusions in 20 HIV-infected individuals were well tolerated with no serious adverse events related to the study drug. After interruption of ART, the median time to meeting protocol criteria to restart therapy was 13 weeks. The median duration of plasma viremia of

Musculoskeletal pathologies (MSPs) such as osteoarthritis (OA) and osteoporosis (OP), are a set of disorders that cause severe pain, motion difficulties, and even permanent disability. In developed countries, the current incidence of MSPs reaches about one in four adults and keeps escalating as a consequence of aging and sedentarism. Interestingly, OA and OP have been closely related to similar risk factors, including aging, metabolic alterations, and inflammation. Visfatin, an adipokine with an inflammatory and catabolic profile, has been associated with several OA and OP metabolic risk factors, such as obesity, insulin resistance, and type II diabetes. Furthermore, visfatin has been associated with the innate immune receptor toll-like receptor 4 (TLR4), which plays a key role in cartilage and bone inflammatory and catabolic responses. Moreover, visfatin has been related to several OA and OP pathologic features. The aim of this work is to bring together basic and clinical data regarding the common role of visfatin in these pathologies and their major shared risk factors. Finally, we discuss the pitfalls of visfatin as a potential biomarker and therapeutic target in both pathologies.

Background:Osteoarthritis (OA) incidence has skyrocketed in the last decade and yet a definitive treatment has still to be found. This worldwide disease is depriving our society from their life quality and has become a grave economic burden. Research on anti-inflammatory tools has been done on traditional Asian medicine. Boswellic acid is a plant-derived molecule from the Boswellia species that has shown to prevent cartilage loss in an OA mouse model[1]. However, the specific mechanism of action is still unclear. The activation of innate immune receptors, such Toll-like receptor 4 (TLR4) has been involved in chondrocyte-mediated inflammatory responses and OA development. Although, boswellic acid has shown an inhibitory effect on TLR4-mediated inflammatory responses little is known about its role on TLR4-mediated chondrocyte inflammatory and catabolic responses.Objectives:Determine the ability of beta boswellic acid (BBA) to block TLR4-mediated innate immune responses in chondrocytes and synoviocytes.Methods:In silicoThe binding affinity of beta boswellic acid (BBA) to TLR4 complex signalling was determined by optimized docking algorithm in the BIO-HPC Research Group facilities.In vitroCellular proteome and secretome profiling (LC-MALDI/TOFF) was used to study inflammatory pathways induced by the agonist of TLR4 (LPS [100ng/ml]) and IL1R (IL1β [0.1ng/ml]). The effect of BBA on TLR4-mediated innate immune responses was determined by RT-PCR, Western Blot and ELISA in primary human OA chondrocytes (hOC), murine ATDC5 chondrocytes, human synoviocytes (SW982) and primary human osteoblasts (hOB). Cell viability was tested using the methyl-thiazolyl-tetrazolium (MTT) reagent. Nitric oxide production in cell culture media was assessed by Griess reaction. Green Malachite Assay was used to semi-quantify the whole phosphoproteome.EthicsThis study was approved by the CEIC (CAEIG 2014/310).Results:Cellular proteome and secretome profiling validated the activation of TLR4 and IL1R signalling by LPS and IL1β ligands and revealed an enrichment in innate immune responses (NF-Kβ, NLRP3, MMPs, Interleukins, etc).Non-toxic doses of BBA [0.5-1000nM] prevented the activation of TLR4 in multiple articular joint cells and inhibited TLR4 & IL1R-dependant innate immune responses at the mRNA and protein level such as inflammatory factors IL6, NOS2, COX2, LCN2, MMP1, -3, -9, -13 and ADAMTS4, among others. Furthermore, NF-Kβ/IKBα and NLRP3/PYCARD/IL1β axis were also severely inhibited after BBA treatment. Moreover, these results were validated by in silico docking analysis that showed BBA interacted with TLR4/NF-Kβ.Conclusion:We prove that BBA inhibit TLR4 & IL1R -dependent innate immune responses in multiple human joint cells (Figure 1). We show that NF-Kβ & NLRP3 signalling, both associated to OA, are blocked (mRNA and protein) after BBA treatment (Figure 1).Our data support previous studies showing the prevention of cartilage loss in an OA animal models by BBA might come from its ability to inhibit TLR4 signalling. In the clinical practice of rheumatologists, Boswellia Serrata could be a useful nutraceutical to manage OA inflammation due to its content in BBA.Figure 1.References:[1]Wang, Q.; Pan, X.; Wong, H.H.; Wagner, C.A.; Lahey, L.J.; Robinson, W.H.; Sokolove, J. Oral and topical boswellic acid attenuates mouse osteoarthritis. Osteoarthr. Cartil.2014, 22, 128–132, doi:10.1016/j.joca.2013.10.012.Acknowledgements:Eloi Franco-Trepat and Ana Lois-Iglesias contributed equally to this work.This research has been funded by the non-profit FER (Fundación Española de Reumatologia /Spanish Foundation of Rheumatology) through the project “Búsqueda de nuevos fármacos bloqueantes de la inflamación asociada a TLR4 en condrocitos humanos artrósicos”.Disclosure of Interests:None declared

Lateral mass screws combined with rods are the standard method for posterior cervical spine subaxial fixation. Several techniques have been described, among which the most used are Roy Camille, Magerl, Anderson and An. All of them are based on tridimensional angles. Reliability of freehand angle estimation remains poorly investigated. We propose a new technique based on on-site spatial references and compare it with previously described ones assessing screw length and neurovascular potential complications. Four different lateral mass screw insertion techniques (Magerl, Anderson, An and the new described technique) were performed bilaterally, from C3 to C6, in ten human spine specimens. A drill tip guide wire was inserted as originally described for each trajectory, and screw length was measured. Exit point was examined, and potential vertebral artery or nerve root injury was assessed. Mean screw length was 14.05 mm using Magerl’s technique, 13.47 mm using Anderson’s, 12.8 mm using An’s and 17.03 mm using the new technique. Data analysis showed significantly longer lateral mass screw length using the new technique (p value

Osteoarthritis (OA), the most common chronic rheumatic disease, is mainly characterized by a progressive degradation of the hyaline articular cartilage, which is essential for correct joint function, lubrication, and resistance. Articular cartilage disturbances lead to joint failure, pain, and disability. Hyaline cartilage is also present in the growth plate and plays a key role in longitudinal bone growth. Alterations of this cartilage by diverse pathologies have been related to longitudinal bone growth inhibition (LBGI), which leads to growth retardation. Diet can play a crucial role in processes involved in the OA and LBGI’s onset and evolution. Specifically, there is ample evidence pointing to the negative impacts of caffeine consumption on hyaline cartilage. However, its effects on these tissues have not been reviewed. Accordingly, in this review, we summarize all current knowledge in the PubMed database about caffeine catabolic effects on articular and growth plate cartilage. Specifically, we focus on the correlation between OA and LBGI with caffeine prenatal or direct exposure. Overall, there is ample evidence indicating that caffeine intake negatively affects the physiology of both articular and growth plate cartilage, increasing consumers predisposition to suffer OA and LBGI. As a result, caffeine consumption should be avoided for these pathologies.

Background The rising prevalence of rheumatic diseases in our society has caused a dramatic impact on the welfare of the population as well as becoming an economic burden to the health system. Osteoarthritis (OA), the most common rheumatic disease, is defined by joint-space narrowing due to progressive cartilage degradation. Despite the growing knowledge in OA pathophysiology, no treatment has yet proved to be efficient enough. The activation of innate immune receptors, such Toll-like receptor 4 (TLR4), by damage-associated molecular patterns (DAMPS) has been involved in chondrocyte-mediated inflammatory responses. There are currently no available drugs aimed to block TLR4-mediated inflammatory responses. Nonetheless, there are already known drugs being employed in other indications that could have this activity; namely amitriptyline, naloxone, and thalidomide. Objectives Determine the ability of amitriptyline, naloxone and thalidomide to block TLR4-mediated innate immune responses in chondrocytes. Methods The effect of amitriptyline, naloxone and thalidomide on TLR4-mediated inflammatory responses was determined in mouse chondrogenic cell line (ATDC5) and in human primary OA chondrocytes. The mRNA expression of key inflammatory factors lipocalin-2 (LCN2), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) was studied by RT-PCR. Cell viability was tested using the methyl-thiazolyl-tetrazolium (MTT) reagent and nitrite accumulation (nitric oxide production) in cell culture media was assessed by Griess reaction and validated by determining nitric oxide synthase 2 (NOS-2) mRNA expression. Results The co-stimulation of human OA chondrocytes with the TLR4 agonist LPS [100 ng/ml] and amitriptyline [1 µM], reduced the mRNA expression of LCN2 (90%), IL-6 (95%) and MCP-1 (87%). The pre-stimulation of naloxone [100 µM] with LPS also reduced the mRNA expression of LCN2 (53%), IL-6 (78%) and MCP-1 (79%). Similar results LCN2 (63%), IL-6 (74%), and MCP-1 (78%) were obtained upon the pre-stimulation of these cells with thalidomide [500 µM]. The anti-inflammatory effect of these drugs on these pro-inflammatory factors was also observed but lowered in ATDC5 cells. Consistent with these results in ATDC5 cells these drugs also reduced the expression of mRNA NOS-2 gene expression as well as nitrite accumulation in the cell culture medium. At the studied concentrations, amitriptyline, naloxone and thalidomide did not affect to chondrocytes viability. Conclusions The data presented here have shown that amitriptyline, naloxone and thalidomide block TLR4 innate immune responses in human OA chondrocytes. These drugs have passed many toxicology and safety tests for their clinical use and could be ready for its repurposing in the management of TLR4-mediated OA cartilage inflammation. Acknowledgements This research is supported by Fondo de Investigacion Sanitaria funded by the Instituto de Salud Carlos III and FEDER (PI16/01870, CP15/00007). R.G. is funded by the Instituto de Salud Carlos III through a Miguel Servet programme. R.G. is a member of the RETICS Programme, RD12/0009/0008 Instituto de Salud Carlos III (ISCIII). Disclosure of Interest None declared

Purpose Antegrade intramedullary nailing is an alternative for humeral shaft fracture treatment. This surgical technique can be especially demanding in some fracture patterns, leading to problems like malunion and non-union. The purpose of our study is to demonstrate that the use of a nail with cerclage wires could be a safe procedure that facilitate reduction, specially in fractures with abduction of the proximal fragment. Materials and methods Fifty-six patients were included, from January 2007 to March 2016. In this cohort forty-two patients were females and eighteen males; mean age was sixty-seven (32–89). The fractures were reduced using a cerclage wire through a small lateral or anterior approach, then, antegrade intramedullary nailing was performed. Fracture healing was established by clinical and radiographic evaluation. Shoulder function was assessed using the Constant Score. Results Fifty-three patients healed (94.6%) adequately. Two patients developed a non-union (3.5%). One patient developed an infection (1.8%). Transient radial nerve palsy was observed in two patients (3.5%). The mean Constant Score at the end of the study was 70 points (range from 34 to 98 points). Conclusions Surgical treatment of humeral shaft fractures with cerclage wire and intramedullary nailing is a safe technique to improve fracture reduction. The use of cerclage wires leads to better bone contact while minimizing malunions. The rate of non-union in our study is lower than the rate reported in the literature for humeral shaft fractures treated by intramedullary nailing alone.

Inflammation is a process whose main function is to fight against invading pathogens or foreign agents. Nonetheless, it is widely accepted that inflammation takes part in multiple processes in a physiological or pathophysiological context. Among these processes the inflammation has been closely related to bone metabolism. It is well-known that in systemic inflammatory diseases such as rheumatoid arthritis the inflammatory environment contributes to the reduction of the bone mineral density. This has been further evidenced in different animals models of osteoporosis where the deletion of key inflammatory molecules dramatically reduced the bone loss. On the contrary, it is also well-known that certain degree of inflammation is required to allow bone fractures healing. In fact, excessive use of anti-inflammatory drugs inhibits bone fracture consolidation. The innate immune responses (IIRs) contribute to the development and maintenance of the inflammation. These responses have been observed in cells of the musculoskeletal system. Chondrocytes and osteoblasts are equipped with the molecular repertoire necessary to setting up these IIR, including the expression of several toll-like receptors. Specifically, toll-like receptor 4 (TLR4) activation in mesenchymal stem cells, osteoblasts, and osteocytes has been involved in catabolic and anabolic process. Accordingly, in this review we have summarized the current knowledge about the physiology of TLR4, including its signaling, and its endogenous agonists. In addition we have focused on its role on osteoblast metabolism and function.

Paget's disease of bone (PDB) is a disease characterized by a disorder in the bone metabolism. The spine is the second region affected after the pelvis. Surgical treatment is reserved for cases refractory to medical treatment. We performed a systematic review of patients with Paget disease of bone affecting the spine, treated surgically in the last 30 years. The main objective of the review is to find out indications for surgery, outcomes of these patients and also the standard perioperative management.

Non-ionizing radiation at 2.45 GHz may modify the morphology and expression of genes that codify heat shock proteins (HSP) in the thyroid gland. Diathermy is the therapeutic application of non-ionizing radiation to humans for its beneficial effects in rheumatological and musculo-skeletal pain processes. We used a diathermy model on laboratory rats subjected to maximum exposure in the left front leg, in order to study the effects of radiation on the nearby thyroid tissue. Fifty-six rats were individually exposed once or repeatedly (10 times in two weeks) for 30 min to 2.45 GHz radiation in a commercial chamber at different non-thermal specific absorption rates (SARs), which were calculated using the finite difference time domain technique. We used immunohistochemistry methods to study the expression of HSP-90 and morphological changes in thyroid gland tissues. Ninety minutes after radiation with the highest SAR, the central and peripheral follicles presented increased size and the thickness of the peripheral septa had decreased. Twenty-four hours after radiation, only peripheral follicles radiated at 12 W were found to be smaller. Peripheral follicles increased in size with repeated exposure at 3 W power. Morphological changes in the thyroid tissue may indicate a glandular response to acute or repeated stress from radiation in the hypothalamic–pituitary–thyroid axis. Further research is needed to determine if the effect of this physical agent over time may cause disease in the human thyroid gland.

Imaging studies, such as high resolution computerized tomography (HRCT) and magnetic resonance imaging (MRI) facilitate the evaluation of mediastinal masses. However, the definite characterization of such masses can be ascertained only after tissue sampling is obtained and analyzed. Some mediastinal masses, like bronchogenic cysts, can be misdiagnosed as solid masses or lymphadenopathy in imaging studies, due to the variable densities of the cyst contents. More invasive tests, like fine needle aspiration or surgical resection of the bronchogenic cyst, may be necessary when HRCT fails to provide an initial diagnosis. We describe two such cases seen at our institution that highlight the implications of establishing a diagnosis of bronchogenic cyst with endobronchial ultrasound (EBUS) - trans-bronchial needle aspiration (TBNA) and discuss the possible therapeutic utility of EBUS-TBNA in select patients with bronchogenic cysts.

Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) constitutes the only curative treatment for myelofibrosis (MF), but its associated toxicity remains high. Prognostic risk models are widely used in clinical practice to select those MF patients who are more likely to benefit from transplantation. Recently, a new prognostic model, the Myelofibrosis Transplant Scoring System (MTSS), has been developed to predict the outcome of MF patients undergoing allo-HCT (Gagelmann N et al, Blood 2019). We aimed to evaluate the performance of such model in an independent series of patients. Methods: This is a retrospective study that included all adult patients who underwent first allo-HCT for MF between January 2005 and May 2019 in 8 Spanish hospitals. Patients transplanted after leukemic transformation were excluded. Survival probability from the time of HCT was estimated by the method of Kaplan-Meier and compared by the log-rank test. Each parameter of the MTSS was tested for its potential association with survival in univariate analysis. Cumulative incidence functions were used to estimate incidence of Graft-versus-Host-Disease (GVHD), Relapse Incidence (RI), and Non-Relapse Mortality (NRM) within a competing risk setting. Statistical analyses were performed with SPSS 19 (SPSS Inc./IBM, Armonk, NY) and R. Results: Demographics and transplant characteristics of the overall series of 107 MF patients are shown in Table 1. After a median follow-up from allo-HCT of 5.3 years, 49 patients (46%) had died. The survival probability at 1, 3, and 5-years was 64.5%, 52%, and 50%, respectively. Transplantation outcome improved over the years. Thus, the survival probability at 3-years was 35% (95% CI: 12-58), 50% (95% CI: 33-67), and 65% (95% CI: 50-80) during the time periods 2005-2009 (n=17), 2010-2014 (n=34), and 2015-2019 (n=56), respectively (P=0.038). The cumulative incidence of grade II-IV acute GVHD at day 100 was 45%. The cumulative incidence of relapse at 1, 3, and 5-years was 16%, 19.5%, and 19.5%, respectively. NRM probability at 1, 3, and 5-years was 24%, 29%, and 31%, respectively. In univariate analysis, the only parameter included in the MTSS that was significantly associated with survival was the Karnofsky performance status < 90% (HR: 1.9, 95% CI: 1.1-3.4; P=0.031). Neither age > 57 years (P=0.68), platelets 25 x 109/L (P=0.38), ASXL1 mutations (P=0.34), non-CALR/MPL driver mutation (P=0.57) nor HLA-mismatched unrelated donor (P=0.22) correlated with survival. Among other classical risk factors for transplant outcome, only a comorbidity index >= 3 was significantly associated with shorter survival (HR: 2.1, 95% CI: 1.1-4; P=0.017). A total of 64 cases had all required clinical and molecular data to calculate the MTSS. Figure 1 shows the survival curves of the different risk groups as defined by the MTSS. As can be seen, the prognostic model was not able to discriminate four risk groups. We then pooled together patients assigned to the low (n=26) and intermediate risk (n=23) groups, and those within the high (n=9) and very high risk (n=6) groups. On this basis, two-categories could be identified: standard risk (n=49 [77% of patients]) and high risk (n=15 [23%]). The 3-year overall survival was 65% (95% CI: 51-79) in the standard risk and 17% (95% CI: 0-46) in the high risk categories (P=0.060)(Figure 2). Conclusions: the MTSS did not discriminate four different risk categories in our series. Both, the limited number of cases and the differences in patients and transplant characteristics in our series as compared to those of the original MTSS cohort might account for this finding. Nevertheless, the MTSS was able to identify a subset of patients with a very poor prognosis after transplantation. Such information could be useful to assist on transplant decision-making. Disclosures Sanchez-Guijo: Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Amgen: Honoraria; Roche: Honoraria. Hernandez Boluda:Incyte: Other: Travel expenses paid.

Juxta-epiphyseal/Salter-Harris fractures are the most common hand fractures in children and the proximal phalanx is involved in most cases. In the absence of soft-tissue interposition, these growth plate injuries are simple to reduce and are stable. However, in some cases, flexor tendon entrapment could be present. We report on an 11-year-old girl who sustained a fall onto her outstretched hand with subsequent injuries in her long, ring, and small fingers. Plain radiographs showed a severely displaced juxta-epiphyseal proximal phalanx fracture in her ring finger associated with mildly displaced juxta-epiphyseal proximal phalanx fractures of the long and small fingers. Fracture reduction could not be achieved after a closed reduction attempt. An open reduction and stabilization using Kirschner wires was performed in the fourth and fifth fingers, because of entrapment of the flexor digitorum profundus tendon. Excellent functional as well as radiological outcomes were achieved. These types of injuries are very uncommon and a high index of suspicion on the basis of clinical as well as radiological findings is needed to make an early diagnosis and for adequate treatment. Multiple proximal phalangeal fractures could be associated with the simultaneous entrapment of flexor tendons in different fingers as in our case; this is important to keep in mind as it is useful when planning the definitive surgical treatment and doing so will have a positive impact on the final functional as well as radiological outcomes.

Ultrasonographic assessment of diaphragm function with patients on low levels of pressure support (PS) predicts extubation outcomes, but similar information regarding extubation success under other conditions is lacking. The purpose of this study was to determine whether ultrasound (US) measurements of the diaphragm made on various levels of PS can predict time until successful extubation. Fifty-six intubated patients underwent ultrasound of the right hemidiaphragm during a PS wean at varying levels of pressure support (PS 5/5 cm of H2O, 10/5 cm of H2O, and 15/5 cm of H2O). The diaphragm was visualized using a 7.5–10 mHz transducer in the zone of apposition of the diaphragm to the lower rib cage. The percent change in diaphragm thickness between end-expiration and end-inspiration (∆tdi%) was calculated at each level of PS. ∆tdi% >20 is a robust predictor of extubation success within 48 h of US at PS 5/5 cm of H2O and 10/5 cm of H2O (sensitivity 84.6 and 88.9 % and specificity 79.0 and 75.0 %, respectively). At PS greater than 10/5 cm of H2O, its predictive power was greatly diminished. Of nine patients who were extubated with ∆tdi% below the cutoff, 66.6 % required emergent reintubation in the next two days. Diaphragm US is a valid predictor of extubation success at some but not all PS settings. Using a ∆tdi% of 20 % on PS levels up to 10/5 cm of H2O may reduce both unnecessarily prolonged intubations and prevent emergent reintubations.

Kienböck's disease is an unusual pathology with unknown aetiology within the pediatric population. Several treatment options have been described in the literature; however, there are neither large series nor homogeneous studies that have clarified which treatment is best. The aim of this study was to describe five cases in which definitive distal radius epiphysiodesis was performed as an alternative method to the classic distal radius shortening osteotomy in skeletally immature patients with Kienböck's disease.The clinical charts and radiographs of four patients (five wrists) diagnosed as having Kienböck's disease and treated by definitive distal radius epiphysiodesis were reviewed.All patients were symptomatically free with full range of motion at 4.25 months (range, three to six months) after surgery. In all cases, shortening of the distal radius was achieved (p = 0.032).This new technique is a simple, effective, and minimally invasive procedure with low morbidity and good clinical and radiological outcomes.

Summary Non-ionizing radiation at 2.45 GHz may modify the expression of genes that codify heat shock proteins (HSP) in the thyroid gland. Using the enzyme-linked immunosorbent assay (ELISA) technique, we studied levels of HSP-90 and HSP-70. We also used hematoxilin eosin to look for evidence of lesions in the gland and applied the DAPI technique of fluorescence to search for evidence of chromatin condensation and nuclear fragmentation in the thyroid cells of adult female Sprague-Dawley rats. Fifty-four rats were individually exposed for 30 min to 2.45 GHz radiation in a Gigahertz transverse electromagnetic (GTEM) cell at different levels of non-thermal specific absorption rate (SAR), which was calculated using the finite difference time domain (FDTD) technique. Ninety minutes after radiation, HSP-90 and HSP-70 had decreased significantly (P

Open fractures constitute a major trauma mostly sustained by young adults during high-energy injuries. Management of long bone open fractures is a very complex issue and is often complicated by nonunion and deep infection being among the most devastating and difficult to cure. It is generally recommended that wound debridement and stabilization of open fractures should be performed as early as possible, preferably within 6-8 h on the basis of historical comment and laboratory data. The rationale for this rule is believed to originate from Freidrich's historical study of guinea pigs. The literature lacks strong evidence addressing the primary issue of timing and delay on the incidence of deep infection and nonunion in open fractures. In the light of the actual literature regarding this topic, it seems that time to debridement of open fractures is not a prognostic factor of infection as well as nonunion.

In 80-year-old woman presented with dyspnea on exertion, present for the last 2 years. She said she became short of breath after walking 1 block. Her medical history was significant only for 35 pack-years of smoking. On examination, her lung fields were clear, with no audible murmurs, and she had

Atherosclerosis and venous thromboembolism share similar pathophysiology based on common inflammatory mediators. The dose-related effect of statin therapy in venous thromboembolism remains controversial. This study investigated whether the use of antiplatelet therapy and statins decrease the occurrence of venous thromboembolism in patients with atherosclerosis.We conducted a retrospective cohort study reviewing 1795 consecutive patients with atherosclerosis admitted to a teaching hospital between 2005 and 2010. Patients who had been treated with anticoagulation therapy were excluded. Patients who either used statins for2 months or never used them were allocated to the nonuser group.The final analysis included 1100 patients. The overall incidence of venous thromboembolism was 9.7%. Among statin users, 6.3% (54/861) developed venous thromboembolism, compared with 22.2% (53/239) in the nonuser group (hazard ratio [HR] 0.24; P.001). After controlling for confounding factors, statin use was still associated with a lower risk of developing venous thromboembolism (HR 0.29; P.001). High-dose statin use (average 50.9 mg/day) (HR 0.25; P.001) lowered the risk of venous thromboembolism compared with standard-dose statins (average 22.2 mg/day) (HR 0.38; P.001). Dual antiplatelet therapy with aspirin and clopidogrel decreased occurrence of venous thromboembolism (HR 0.19; P.001). Interestingly, combined statins and antiplatelet therapy further reduced the occurrence of venous thromboembolism (HR 0.16; P.001).The use of statins and antiplatelet therapy is associated with a significant reduction in the occurrence of venous thromboembolism with a dose-related response of statins.

A case of body stalk anomaly which was diagnosed at 17 weeks of gestation is presented on a second trimester sonography after an abnormal first trimester scan and second opinion review. The fetus displayed multiple anomalies characteristic of body stalk syndrome including abdominal wall defect (omphalocele), kyphoscoliosis, fetal dismorphology and a two vesseled umbilical cord. Body stalk anomaly is a rare congenital anomaly with a series of similar clinical manifestations and poor prognosis.

Physical agents such as non-ionizing continuous-wave 2.45GHz radiation may cause damage that alters cellular homeostasis and may trigger activation of the genes that encode heat shock proteins (HSP). We used Enzyme-Linked ImmunoSorbent Assay (ELISA) and immunohistochemistry to analyze the changes in levels of HSP-90 and its distribution in the brain of Sprague-Dawley rats, ninety minutes and twenty-four hours after acute (30min) continuous exposure to 2.45GHz radiation in a the Gigahertz Transverse Electromagnetic (GTEM cell). In addition, we studied further indicators of neuronal insult: dark neurons, chromatin condensation and nucleus fragmentation, which were observed under optical conventional or fluorescence microscopy after DAPI staining. The cellular distribution of protein HSP-90 in the brain increased with each corresponding SAR (0.034 ± 3.10-3, 0.069 ± 5.10-3, 0.27 ± 21.10-3 W/kg), in hypothalamic nuclei, limbic cortex and somatosensorial cortex after exposure to the radiation. At twenty-four hours post-irradiation, levels of HSP-90 protein remained high in all hypothalamic nuclei for all SARs, and in the parietal cortex, except the limbic system, HSP-90 levels were lower than in non-irradiated rats, almost half the levels in rats exposed to the highest power radiation. Non-apoptotic cellular nuclei and a some dark neurons were found ninety minutes and twenty-four hours after maximal SAR exposure. The results suggest that acute exposure to electromagnetic fields triggered an imbalance in anatomical HSP- 90 levels but the anti-apoptotic mechanism is probably sufficient to compensate the non-ionizing stimulus. Further studies are required to determine the regional effects of chronic electromagnetic pollution on heat shock proteins and their involvement in neurological processes and neuronal damage.

Jorge I Mora1, Denis Hadjiliadis21Albert Einstein Medical Center, Philadelphia, PA, USA; 2Hospital of the University of Pennsylvania, Philadelphia, PA, USAAbstract: Medical treatment of emphysema does not alter the natural progression of the disease. Surgical techniques are an attractive conceptual approach to treat hyperinflation in these patients. Lung volume reduction surgery and lung transplantation are appropriate therapeutic options for a selected population with emphysema. We will review the available evidence to support these approaches.Keywords: COPD, emphysema, lung volume reduction, lung transplantation

The aim of the present study was to analyse dietary habits and fluid intake of professional basketball players with consideration of dietary guidelines and sport nutrition recommendations. A dietary habit questionnaire including a 24 h recall was recorded by 55 elite basketball players of the first Spanish Basketball League. Energy consumption among these athletes was high 17.7 ±0.9 MJ · day –1 in comparison to other elite team sport athletes. Furthermore intakes of protein, fat, saturated fatty acids mineral and most vitamins exceed the current Daily Recommended Intakes (DRI’s) for these macronutrients whereas, intakes of carbohydrate and vitamin E failed to meet the guidelines. Daily fluid intake was 3126 ±1226ml. Water was the preferred beverage (1688±1032 ml), followed by milk (445 ±521 ml), commercial sport drinks (377 ±520 ml), carbonated beverages (307 ±492 ml), juices (150 ±208 ml), beer (67 ±189 ml), non-alcoholic (beer 49 ±158 ml) and wine (43 ±218 ml). Sixty-six percent of the participants repo...

Aims. To describe the craniofacial morphology of a group of patients with Down's syndrome using a cephalometric analysis of the lateral skull radiograph. Materials and methods. The studied sample consisted of 39 patients with Down's syndrome (24 boys, 15 girls) ranging from 7 to 18 years of age. The computerized cephalometric study of the lateral skull radiograph of each patient was carried out using the method described by Ricketts. Results.Anterior cross-bite was observed in 38.4% of patients and diminished interincisal angle in 77%. Skeletal parameters matched the clinical norm, indicating mesofacial biotype, i.e., normal maxillomandibular growth. The lower incisors protruded in 84.6% of the individuals studied and were proinclined in 77%; upper incisors were protruded in 77% of the sample. The lower lip protruded in 84.6%. Analysis of craniofacial parameters showed average values within the clinical norm. Analysis of the inner cranium demonstrated normal inclination of the cranial base, while the length of the anterior skull base was diminished in 53.8%. Conclusions. From the skeletal perspective, patients with Down's syndrome who are in a period of growth demonstrate a reduction of the anterior skull base. From the dentoalveolar perspective, they show protrusion and proinclination of lower incisors, which is related to a tendency to anterior cross-bite and, to a lesser extent, to diminished overbite. Likewise, the lower lip protrusion observed in this study is related to the position of the lower incisor.

Periprosthetic knee fractures following total knee arthroplasty are increasing proportionally to the number of primary procedures done. We performed a retrospective review of Rorabeck type II fractures treated with a retrograde nail, trying to find the relationship between failure and the number of distal locking screws used. Twenty-six patients were included. The number of distal interlocking screws (patients with one or two distal interlocking screws and patients with three screws) correlated with nonunion (p0.1), did not correlate with the malunion rate (p0.1) and correlated with the reintervention rate (p0.1).

La secuencia de perfusion arterial reversa (TRAP) es una malformacion congenita exclusiva de gemelos monocoriales, con una incidencia aproximada de 1/35.000 embarazos. La malformacion primaria es la ausencia de una estructura cardiaca en un gemelo, que se comporta como un parasito hemodinamicamente dependiente de su co-gemelo, a traves de una anastomosis placentaria arterio-arterial. Lahistoria natural conlleva una alta tasa de mortalidad perinatal del gemelo sano, principalmente por falla cardiaca y polihidramnios. Por su alta morbi-mortalidad, se ha intentado realizar intervenciones intrautero para minimizar complicaciones del gemelo normal, deteniendo la circulacion del gemelo acardico cuando esta indicado. Se presenta uncaso de una femenina de 30 anos, obesa, tabaquista, hipertensa en control con enalapril y amlodipina, primigesta, con embarazo multiple monocorial-biamniotico, en quien en ultrasonido control a los 4 meses de edad gestacionalevidencio una malformacion severa por un fetoacardico. La paciente requirio intervencionintrautero a las 28 semanas de gestacion, serealizo oclusion del cordon umbilical parafeticidio selectivo del gemelo acardico, guiado por ultrasonido.

Objective The purpose of this study is to compare the biocompatibility and the effect in osteoblasts of polymethyl methacrylate alone, and mixed with hydroxyapatite in different concentrations of 5, 10, 15 and 20%, without exceeding 20%, as it can alter mechanical properties of the composite. Materials and methods Experimental study comparing osteoblast response to polymethyl methacrylate alone and with hydroxyapatite in different concentrations. Results Composites at 15 and 20% obtained better osteoblast response, with higher osteoblastic activity markers, and lower apoptosis markers. Electron microscopy images show improved adhesion of osteoblasts.

There are several trajectories described for the insertion of screws in the lateral facets of the cervical spine (Magerl, An, Anderson, based on spinous processes,..), they all rely on milimeters and precise angles; but anatomical variety (osteophytes, mass anatomy, spinous process deformities...) might render them not fully reproducible. It is proposed to consider the lateral mass as an slanted cube rotated to present a crest stright posterior, and define a trajectory as close to the 3D diagonal as possible from inferomedial corner at dorsal-medial facet to the anterosuperior cornar of the antero-lateral facet of such a cube.HypothesisThat trajectory is free of biass and represents the longest posible one in a cubic body, so obtaining the strongest anchor possible.Material and Methods10 cervical spines (dry bone) from thew Anatomy Department of Santiago de Compostela University were gathered and 4 different trajectories were developed in each lateral mass from C3 to C6 (both sides) so getting 320 differe...

Non-ionizing radiation at 2.45 GHz may modify the expression of genes that codify heat shock proteins (HSP) in the thyroid gland. Using the Enzyme-Linked ImmunoSorbent Assay (ELISA) technique, we studied levels of HSP-90 and HSP-70. We also used hematoxilin eosin to look for evidence of lesions in the gland and applied the DAPI technique of fluorescence to search for evidence of chromatin condensation and nuclear fragmentation in the thyroid cells of adult female Sprague-Dawley rats. Fifty-four rats were individually exposed for 30 min to 2.45 GHz radiation in a Gigahertz Transverse Electromagnetic (GTEM) cell at different levels of non-thermal SAR, which was calculated using the FDTD technique. Ninety minutes after radiation, HSP-90 and HSP-70 had decreased significantly (p

Distal radius fractures are a common disorder in industrialized nations associated with osteoporosis, with a reported incidence of two fractures per thousand patients per year. We performed a retrospective study comparing two sets of 40 patients, with fracture of the distal radius treated with Penning external fixator, compared to 40 patients treated with fixed-angle volar-locking plate (Plate Depuy ® DVR), with the objective of finding differences between both treatment methods in anatomical values, functional outcomes and complication rates. All fractures were classified according to the AO classification. Postero-anterior and lateral radiographs of the wrist were taken after fracture, after surgery and at 6 months after surgery. We also assessed functional outcome. Minimum follow up was of 10 months. We compared complications between both groups. In the group of patients treated with fixed-angle volar-locked plate, radiological results are found to be closer to the anatomical references. Final outcomes revealed similar functional scores between both groups. The complications rate was statistically higher in the group of patients who underwent external fixation. In the fixed-angle volar-locked plate group, most of complications were related to patient discomfort due to the volar-locking plate.