Nonreferral of Possible Soft Tissue Sarcomas in Adults: A Dangerous Omission in Policy

Introduction. The aim of this study is to compare outcomes in three groups of STS patients treated in our specialist centre: patients referred immediately after an inadequate initial treatment, patients referred after a local recurrence, and patients referred directly, prior to any treatment. Patients and methods. We reviewed all our nonmetastatic extremity-STS patients with a minimum follow-up of 2 years. We compared three patient groups: those referred directly to our centre (group A), those referred after an inadequate initial excision (group B), and patients with local recurrence (group C). Results. The study included 174 patients. Disease-free survival was 73%, 76%, and 28% in groups A, B, and C, respectively (P < .001). Depth, size, and histologic grade influenced the outcome in groups A and B, but not in C. Conclusion. Initial wide surgical treatment is the main factor that determines local control, being even more important than the known intrinsic prognostic factors of tumour size, depth, and histologic grade. The influence on outcome of initial wide local excision (WLE), which is made possible by referral to a specialist centre, is paramount

Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow up of a multicenter randomized controlled clinical trial (phase I/II)

Background: Mesenchymal stromal cells (MSCs) are a promising option to treat knee osteoarthritis (OA). Their safety and usefulness have been reported in several short-term clinical trials but less information is available on the longterm efects of MSC in patients with osteoarthritis. We have evaluated patients included in our previous randomized clinical trial (CMM-ART, NCT02123368) to determine their long-term clinical efect. Materials: A phase I/II multicenter randomized clinical trial with active control was conducted between 2012 and 2014. Thirty patients diagnosed with knee OA were randomly assigned to Control group, intraarticularly administered hyaluronic acid alone, or to two treatment groups, hyaluronic acid together with 10×106 or 100×106 cultured autol‑ ogous bone marrow-derived MSCs (BM-MSCs), and followed up for 12 months. After a follow up of 4 years adverse efects and clinical evolution, assessed using VAS and WOMAC scorings are reported. Results: No adverse efects were reported after BM-MSCs administration or during the follow-up. BM-MSCs-adminis‑ tered patients improved according to VAS, median value (IQR) for Control, Low-dose and High-dose groups changed from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 7 (6, 7), 2 (2, 5) and 3 (3, 4), respectively at the end of follow up (Low-dose vs Control group, p=0.01; High-dose vs Control group, p=0.004). Patients receiving BM-MSCs also improved clinically accord‑ ing to WOMAC. Control group showed an increase median value of 4 points (−11;10) while Low-dose and Highdose groups exhibited values of −18 (−28;−9) and −10 (−21;−3) points, respectively (Low-dose vs Control group p=0.043). No clinical diferences between the BM-MSCs receiving groups were found. Conclusions: Single intraarticular injection of in vitro expanded autologous BM-MSCs is a safe and feasible proce‑ dure that results in long-term clinical and functional improvement of knee OA

Preneoplastic somatic mutations including MYD88(L265P) in lymphoplasmacytic lymphoma

Normal cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B lymphocytes before lymphoma remains uncertain. We sequenced multiple stages of the B lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of the high prevalence of mutated MYD88. We observed similar accumulation of random mutations in B lineages from both cohorts and unexpectedly found MYD88(L265P) in normal precursor and mature B lymphocytes from patients with lymphoma. We uncovered genetic and transcriptional pathways driving malignant transformation and leveraged these to model lymphoplasmacytic lymphoma in mice, based on mutated MYD88 in B cell precursors and BCL2 overexpression. Thus, MYD88(L265P) is a preneoplastic event, which challenges the current understanding of lymphomagenesis and may have implications for early detection of B cell lymphomas

Inyección intraarticular de células madre mesenquimales autólogas derivadas de médula ósea en el tratamiento de la artrosis de rodilla: Ensayo clínico multicéntrico aleatorizado (Fase I/II)

El objetivo principal de este ensayo clínico es determinar la seguridad y viabilidad del tratamiento de la artrosis de rodilla mediante la administración intraarticular de BM-MSCs autólogas junto con ácido hialurónico (AH). Como objetivo secundario queremos determinar la eficacia terapéutica del tratamiento intraarticular con BM-MSCs autólogas en combinación con AH en pacientes con artrosis de rodilla, mediante la utilización de dos dosis celulares diferentes y comparándolo con el tratamiento aislado de AH. La determinación de la eficacia se realizará utilizando como variables principales del estudio: 1) Escalas clínicas de dolor y funcionalidad. 2) Valoración radiológica utilizando radiología simple y resonancia magnética. Las técnicas y escalas se detallan en la metodología del ensayo

Hip Preservation Surgery in Osteoarthritis Prevention: Potential Benefits of the Radiographic Angular Correction

Objective: The aim of the study is to describe the morphology associated with the development of osteoarthritis (OA) in three different age groups. These data will contribute to defining the morphology associated with early and late hip OA. Methods: We studied 400 hips in 377 patients who had undergone primary THA due to idiopathic OA. Three groups were compared: group 1 (n = 147), younger patients, aged up to 60 years; group 2 (n = 155), patients aged between 61 and 74 years; and group 3 (n = 98), aged 75 or over. Five independent researchers measured the hip angles and the mean values were used to build a database. Results: No differences between groups in sex distribution and BMI were detected. Less coverage of the head (extrusion index), higher T&ouml;nnis angle, lower Wiberg and alpha angles characterized early OA hips. These differences increased with age, being greater between group 2 and group 3 (p &lt; 0.01). However, significant differences were still present in the comparison between group 1 and group 2 (p &lt; 0.01)). No differences were detected between group 2 and group 3. Conclusion: Elevated acetabular angle, head extrusion and decreased Wiberg angle characterize hip osteoarthritis at younger ages and should be the focus of hip preservation surgery in terms of osteoarthritis prevention. Pincer-type FAI (higher Wiberg and lower T&ouml;nnis angle) and higher alpha angle (CAM) are correlated with the development of later OA. These results shed doubt on applying the hip preservation surgery concept in terms of osteoarthritis prevention in FAI, especially in Pincer-type FAI patients

Do we really improve life quality after total knee arthroplasty in patients with Parkinson’s disease?

Introduction The knee in Parkinson’s disease (PD) patients is a problematic joint due to pain, stifness and gait instability. The aim of this study is to evaluate the functional outcome and degree of pain relief achieved after total knee arthroplasty (TKA) in PD patients. Materials and methods This is a retrospective review of 26 PD patients (32 knees) with osteoarthritis who underwent a TKA between 1994 and 2013. Comorbidities, anesthetic procedures and complications were recorded. Patient functional status was assessed with the Knee Society Function Score (KFS) and the Knee Society Score (KSS). PD stage was classifed with the Hoehn and Yahr Scale. Results The mean follow-up was 3.5 years (range 2–9). The mean age was 71 years (range 61–83) with a mean time since PD diagnosis of 11.8 years (range 4–24). PD severity on the Hoehn and Yahr Scale was 1.5 points before surgery and 2 points postoperatively. Pain on the visual analogic scale improved from 8 points preoperatively to 5 points at 1-year follow-up; function improved from 32 (range 20–45) to 71 (range 50–81) and from 34 (range 28–52) to 59 (range 25–76) on the KSS and KFS, respectively. The mean postoperative hospital stay was 9.8 days (range 5–21). Confusion and fexion contracture were the most frequent perioperative complications. Conclusion TKA successfully provided pain relief in PD patients. However, the functional outcome is related to disease progression and, therefore, variable. Perioperative complications are difcult to avoid and manage

Clinical Value of NGS Genomic Studies for Clinical Management of Pediatric and Young Adult Bone Sarcomas

Genomic techniques enable diagnosis and management of children and young adults with sarcomas by identifying high-risk patients and those who may benefit from targeted therapy or participation in clinical trials. Objective: to analyze the performance of an NGS gene panel for the clinical management of pediatric sarcoma patients. We studied 53 pediatric and young adult patients diagnosed with sarcoma, from two Spanish centers. Genomic data were obtained using the Oncomine Childhood Cancer Research Assay, and categorized according to their diagnostic, predictive, or prognostic value. In 44 (83%) of the 53 patients, at least one genetic alteration was identified. In 80% of these patients, the diagnosis was obtained (n = 11) or changed (n = 9), and thus genomic data affected therapy. The most frequent initial misdiagnosis was Ewing’s sarcoma, instead of myxoid liposarcoma (FUS-DDDIT3), rhabdoid soft tissue tumor (SMARCB1), or angiomatoid fibrous histiocytoma (EWSR1-CREB1). In our series, two patients had a genetic alteration with an FDA-approved targeted therapy, and 30% had at least one potentially actionable alteration. NGS-based genomic studies are useful and feasible in diagnosis and clinical management of pediatric sarcomas. Genomic characterization of these rare and heterogeneous tumors also helps in the search for prognostic biomarkers and therapeutic opportunities

Anisotropic cryostructured collagen scaffolds for efficient delivery of RhBMP−2 and enhanced bone regeneration

In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP–2, BMP–7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP–2. In vitro, both scaffolds presented similar mechanical properties, rhBMP–2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP–2 mediated bone healing