Impacto Laboral, Económico, y Clínico Funcional en la Artrodesis Lumbar / Labor, economic, and clinical functional impact of lumbar arthrodesis

Introducción: El dolor lumbar, constituye un grave problema de salud, en España ocupa el primer puesto como causa de Incapacidad Temporal (IT). Diversos estudios han intentado responder a la cuestión de si compensa realizar intervenciones más intensivas. El objetivo del proyecto es analizar el gasto sanitario ocasionado, valorando los costes de IT al emplear el tratamiento conservador y con tratamiento quirúrgico. Material y Métodos: Estudio prospectivo comparativo entre pacientes con patología degenerativa lumbar tratados quirúrgicamente, y de manera conservadora. Se recogieron la edad y sexo, hábitos tóxicos, tratamiento farmacológico, actividad laboral, los segmentos afectados, y el número de días en situación de IT, con un seguimiento de 3 años. Resultados: Un total de 94 pacientes fueron incluidos en el estudio (55 pertenecían al grupo control, y 39 al grupo artrodesis). Los pacientes que fueron operados llevaban más días de IT, y entrañaban más costes de IT (p=0,018). Comparando los costes de la intervención quirúrgica para el grupo artrodesis vemos que no existen diferencias entre los pacientes jubilados/ en situación de incapacidad permanente. Después de tres años de seguimiento, el 89,1% del grupo control y el 52,6% del grupo artrodesis recibieron el alta. Conclusión: Los costes de incapacidad transitoria fueron mayores en los pacientes sometidos a tratamiento quirúrgico. Los pacientes que no recibieron el alta supusieron mayores costes de IT. En los pacientes que recibieron el alta no hubo diferencias en los costes, descontando el coste del proceso quirúrgico. (AU)

Introduction: Low back pain is a serious health problem, and in Spain it occupies first place as a cause of Temporary Disability (TD). Several studies have tried to answer the question of whether it is worthwhile to carry out more intensive interventions. The project aims to analyze the health care costs incurred, assessing the costs of TD when conservative treatment and surgical treatment are used. Material and methods: Prospective comparative study between patients with lumbar degenerative pathology treated surgically and conservatively. Age and sex, toxic habits, pharmacological treatment, work activity, affected segments, and the number of days on TI were recorded, with a follow-up of 3 years. Results: A total of 94 patients were included in the study (55 belonged to the control group and 39 to the arthrodesis group). Patients who underwent surgery had more days of TD and more TD costs (p=0.018). Comparing the costs of surgery for the arthrodesis group, we see that there are no differences between retired/permanently disabled patients. After three years of follow-up, 89.1% of the control group and 52.6% of the arthrodesis group were discharged. Conclusion: Transitional disability costs were higher in patients who underwent surgical treatment. Patients who were not discharged had higher TD costs. In patients who were discharged, there were no differences in costs, discounting the cost of the surgical process. (AU)

Lower estimated glomerular filtration rate at admission is associated with a worse outcome in older patients with hip fracture who undergo surgical treatment.

BACKGROUND: We assessed the relationship of estimated glomerular filtration rate values at hospital admission on the outcome of surgically treated older adults who had suffered a hip fracture. METHODS: Prospective study that included patients > 65 years of age, surgically treated for primary hip fracture, with no pathologic or high-energy trauma aetiology admitted to a tertiary teaching hospital between 2018 and 2019. We stratified patients based on their estimated glomerular filtration rate at admission and examined its association to demographic and clinical variables, including 90-day post-discharge mortality. RESULTS: The study included 942 hip fracture patients. Lowered estimated glomerular filtration rate was significantly associated to a worsening of the functional status, higher incidence of medical postoperative complications, higher postoperative renal dysfunction, and greater number of blood transfusions. Mortality displayed a staircase pattern, increasing with decreasing estimated glomerular filtration rate. Patients with estimated glomerular filtration rate <60 had significantly higher mortality at 90 days after discharge. In-hospital mortality rate was 10.7% in hip fracture patients with chronic kidney disease who experienced a significant variation in the estimated glomerular filtration rate (>5 mL/min/1.73m2) on admission in comparison to baseline values. CONCLUSION: Older adult patients treated for hip fracture with lower glomerular filtration rate values have poorer functional status and worse prognosis. A significant clinical variation of estimated glomerular filtration rate upon hospital admission for hip fracture may be associated with increased in-hospital mortality of chronic kidney disease patients.

Autologous mesenchymal stem cell transplantation for spinal fusion: 10 years follow-up of a phase I/II clinical trial.

Posterolateral spinal fusion is the standard surgical approach for patients with degenerative disc disease. In our previously published article, we reported a 5-years follow-up of a phase I/II clinical trial in patients undergoing spinal fusion with autologous mesenchymal stem cells (MSCs) embedded in tricalcium phosphate. In the current manuscript, we have updated the results with a 10-year follow-up, the longest reported to date in this setting. After clinical and radiological evaluation, safety of the procedure was further confirmed in all 11 treated patients, with no evidence of tumor, infection, inflammatory reaction, or heterotopic ossification related to the administration of MSCs. Regarding clinical efficacy, low back pain and radicular pain (both assessed by the visual analogue scale-VAS), and the Owestry Disability Index remained significantly lower compared to pre-intervention. Radiologic evaluation demonstrated spinal fusion in all cases, improving over time. Finally, quality of life improved significantly also during follow-up. In summary, the use of tricalcium phosphate-embedded autologous MSCs with lumbar posterolateral arthrodesis is safe and potentially provides long-term benefits for 10 years.

El filtrado glomerular bajo al ingreso se relaciona con un peor pronóstico en pacientes mayores con fractura de cadera tratados quirúrgicamente / Lower estimated glomerular filtration rate at admission is associatedwith a worse outcome in older patients with hip fracture who undergosurgical treatment

Fundamento: Evaluar la influencia de los valores de filtrado glomerular estimado (eFG) al ingreso en el pronóstico de los pacientes mayores con fractura de cadera tratados quirúrgicamente.Métodos: Estudio prospectivo de pacientes >65 años, tratados quirúrgicamente por una fractura de cadera primaria, sin etiología tumoral o traumatismo de alta energía, en un hospital universitario terciario entre 2018 y 2019. Estratificamos a los pacientes según el FG al ingreso y estudiamos su asociación con distintas variables demográficas y clínicas, incluida la mortalidad hasta 90 días después del alta hospitalaria.Resultados: Se incluyeron 942 pacientes. La disminución del eFG se asoció significativamente a peor estado funcional, mayor incidencia de complicaciones médicas postoperatorias, mayor disfunción renal postoperatoria y mayor necesidad de transfusión sanguínea. La mortalidad mostró un patrón en escalera que aumentaba con la disminución del eFG. A los 90 días, la mortalidad fue significativamente mayor en pacientes con eFG <60. Los pacientes con enfermedad renal crónica que sufrían una fractura de cadera y experimentan al ingreso una variación significativa del eFG (>5 mL/min/1,73m2) respecto a los valores basales mostraron una tasa de mortalidad intrahospitalaria del 10,7%.Conclusiones: Los pacientes ancianos tratados quirúrgicamente por fractura de cadera con valores más bajos de tasa de eFG presentan peor estado funcional y peor pronóstico. Una variación clínica significativa del FG (>5) en el momento del ingreso hospitalario tras una fractura de cadera podría asociarse a un aumento de la mortalidad intrahospitalaria de los pacientes con insuficiencia renal crónica.(AU)

Background: We assessed the relationship of estimated glomerular filtration rate values at hospital admission on the outcome of surgically treated older adults who had suffered a hip fracture. Methods: Prospective study that included patients > 65 years of age, surgically treated for primary hip fracture, with no pathologic or high-energy trauma aetiology admitted to a tertiary teaching hospital between 2018 and 2019. We stratified patients based on their estimated glomerular filtration rate at admission and examined its association to demographic and clinical variables, including 90-day post-discharge mortality. Results: The study included 942 hip fracture patients. Lowered estimated glomerular filtration rate was significantly associated to a worsening of the functional status, higher incidence of medical postoperative complications, higher postoperative renal dysfunction, and greater number of blood transfusions. Mortality displayed a staircase pattern, increasing with decreasing estimated glomerular filtration rate. Patients with estimated glomerular filtration rate <60 had significantly higher mortality at 90 days after discharge. In-hospital mortality rate was 10.7% in hip fracture patients with chronic kidney disease who experienced a significant variation in the estimated glomerular filtration rate (>5 mL/min/1.73m2 ) on admission in comparison to baseline values. Conclusion: Older adult patients treated for hip fracture with lower glomerular filtration rate values have poorer functional status and worse prognosis. A significant clinical variation of estimated glomerular filtration rate upon hospital admission for hip fracture may be associated with increased in-hospital mortality of chronic kidney disease patients.(AU)

Long-Term Results of a Phase I/II Clinical Trial of Autologous Mesenchymal Stem Cell Therapy for Femoral Head Osteonecrosis.

(1) Background: Osteonecrosis of the femoral head (ONFH) is characterized by impaired vascularization with ischemia resulting in bone cell death, leading to the deterioration of the hip joint. Mesenchymal stem/stromal cells (MSCs) are an attractive potential therapeutic approach in this setting. The aim of this study is to evaluate the clinical improvement in terms of pain and quality of life, as well as the safety of the procedure during the follow-up of patients. (2) Methods: A Phase I-II Open-Label Non-Randomized Prospective clinical trial was conducted. Eight patients with idiopathic ONFH and stage < IIC in the ARCO classification were included. Four weeks before therapy, 40 mL of autologous bone marrow was obtained, and MSCs were expanded under Good-Manufacturing-Practice (GMP) standards. Study medication consisted of a suspension of autologous BM-derived MSCs (suspended in a solution of 5-10 mL of saline and 5% human albumin) in a single dose of 0.5-1 × 106 cells/kg of the patient, administered intraosseously with a trocar and under radioscopic control. Per-protocol monitoring of patients included a postoperative period of 12 months, with a clinical and radiological assessment that included the visual analog scale (VAS), the Harris scale, the SF-36, and the radiological evolution of both hips. In addition, all patients were further followed up for eight years to assess the need for long-term total hip replacement (THR) surgery. (3) Results: Median age of patients included was 48.38 ± 7.38 years, and all patients were men. Autologous MSCs were expanded in all cases. There were no adverse effects related to cell administration. Regarding efficacy, both VAS and ODI scores improved after surgery. Radiologically, 12.5% of patients improved at the end of follow-up, whereas 50% improved clinically. No adverse effects related to the procedure were recorded, and none of the patients needed THR surgery within the first year after MSC therapy. (4) Conclusions: The use of autologous MSCs for patients with ONFH disease is feasible, safe in the long term, and potentially effective.

Therapeutic potential of mesenchymal stromal/stem cells in critical-care patients with systemic inflammatory response syndrome.

BACKGROUND: Despite notable advances in the support and treatment of patients admitted to the intensive care unit (ICU), the management of those who develop a systemic inflammatory response syndrome (SIRS) still constitutes an unmet medical need. MAIN BODY: Both the initial injury (trauma, pancreatitis, infections) and the derived uncontrolled response promote a hyperinflammatory status that leads to systemic hypotension, tissue hypoperfusion and multiple organ failure. Mesenchymal stromal/stem cells (MSCs) are emerging as a potential therapy for severe ICU patients due to their potent immunomodulatory, anti-inflammatory, regenerative and systemic homeostasis-regulating properties. MSCs have demonstrated clinical benefits in several inflammatory-based diseases, but their role in SIRS needs to be further explored. CONCLUSION: In the current review, after briefly overviewing SIRS physiopathology, we explore the potential mechanisms why MSC therapy could aid in the recovery of this condition and the pre-clinical and early clinical evidence generated to date.

Anterior cruciate ligament innervation in primary knee osteoarthritis.

OBJECTIVE: To relate the Anterior Cruciate Ligament (ACL) innervation and histologic degeneration status to the knee osteoarthritis radiologic and functional status. DESIGN: Prospective observational study including 30 consecutive patients affected by primary knee osteoarthritis undergoing Total Knee Arthroplasty (TKA). All patients suffering secondary knee osteoarthritis, an antecedent of an infectious process, malignant process, autoimmune disorder, or previous knee surgery were excluded. We recorded biodemographic, clinical, and radiologic variables of all participants previous to the TKA procedure. ACL tissue was harvested during TKA standard procedure and the obtained sample was fixed in 4% formalin and paraffin-embedded. ACL cross-sections were stained by haematoxylin-eosin and Gallego staining for elastic and collagen fibers, and Sevier-Munger silver staining for nervous tissue. RESULTS: ACL samples histologic degeneration classification reported 15.4% normal, 23.1% slight, 26.9% mild, 11.5% moderate and 23.1% marked. We noted 46.2% large nervous fascicles, 15.4% medium fascicles, 3.8% small fascicles, and no nerve fibers were found in 34.6% ACL samples. No significant correlation was found between the histologic degeneration and the nervous fiber quantification (p>0.05, in all cases). We noted a significant histologic degeneration inverse correlation with the VAS scale (p=0.016), and nervous fiber quantification correlation with Lequesne maximum distance walked punctuation (p=0.043). We also noted greater nervous fiber quantification with minor radiological knee osteoarthritis (Kellgren-Lawrence grade II). CONCLUSIONS: ACL degeneration and innervation deficit may play a role in primary knee osteoarthritis onset, but the lack of a defining relationship among the different parameters assessed justifies further research in greater populations.

Long-term efficacy of autologous bone marrow mesenchymal stromal cells for treatment of knee osteoarthritis.

Knee osteoarthritis is the most prevalent joint disease and a frequent cause of pain, functional loss and disability. Conventional treatments have demonstrated only modest clinical benefits whereas cell-based therapies have shown encouraging results, but important details, such as dose needed, long-term evolution or number of applications required are scarcely known. Here we have reanalyzed results from two recent pilot trials with autologous bone marrow-derived mesenchymal stromal cells using the Huskisson plot to enhance quantification of efficacy and comparability. We find that cell doses of 10, 40 and 100 million autologous cells per knee provided quite similar healing results and that much of the effect attained 1 year after cell application remained after 2 and 4 years. These results are encouraging because they indicate that, apart from safety and simplicity: (i) the beneficial effect is both significant and sizeable, (ii) it can be achieved with a single injection of cells, and (iii) the effect is perdurable for years.Trial registration: EudraCT 2009-017405-11; NCT02123368. Registered 25 April 2014-Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT02123368?term=02123368&draw=2&rank=1.

Quality assessment of orthopedic surgery referral request letters from primary care consultation: Evaluation of a Spanish healthcare area.

BACKGROUND: One of the most requested referrals for specialist consultations from primary care (PC) is orthopedic surgery (OS). The purpose of this work was to analyze the number, characteristics, and quality of PC referral request letters in a Spanish healthcare area to their OS reference department. MATERIALS AND METHODS: The referral rates for 10 years were collected, and a total of 6,225 referral letters issued during the first half of 2019 were analyzed in detail. Gender, age, patient provenance, as well as priority and other process descriptors (type of pathology, suspected diagnosis, exploratory signs, imaging tests) were assessed. A scoring system was developed to evaluate the quality of the referral to an OS consultation: Quality evaluation in OS (QEOS) model. RESULTS: The rate of referral to OS is rising. The mean age of the referred patient was 53 years and 59.3% were women. Degenerative pathologies justified most referral requests (65.7%), most of which related to the spine (24.2%) or the knee (23.2%). In the QEOS analysis of the referral request letters, we noted that only 36.5% described some physical exploration, 32.9% image tool request, 25.8% indicated the pharmacological treatment, and 11.2% subsequent physiotherapy, resulting in a poor average quality of PC to OS patient referral. CONCLUSION: There is a growing demand for patient referral from PC to OS, however, the number, content, and quality of referral request letters varies greatly. The QEOS tool can be the germ of a simple evaluation system that would help in the improvement of the process of continuous care.

MSCs from polytrauma patients: preliminary comparative study with MSCs from elective-surgery patients.

BACKGROUND: Polytrauma is a major clinical problem due to its impact on morbidity and mortality, especially among the younger population. Its pathophysiology is not completely elucidated, and the study of the involvement of certain cell populations with therapeutic potential, such as mesenchymal stromal cells (MSCs), is an area of growing interest, as mesenchymal cells have anti-inflammatory, immunoregulatory, and osteogenic potential. METHODS: In the present preliminary work, we have evaluated the characteristics of MSCs in terms of proliferation, immunophenotype, cell cycle, clonogenic capacity, and multilineage differentiation ability in a series of 18 patients with polytrauma and compared them to those from otherwise healthy patients undergoing elective spinal surgery. RESULTS: MSCs from polytrauma patients displayed higher proliferative potential with significantly higher cumulative population doublings, increased expression of some important cell adhesion molecules (CD105, CD166), and an early pre-osteogenic differentiation ability compared to those of the control group. CONCLUSIONS: MSCs could potentially be of help in the repair process of polytrauma patients contribute to both cell-tissue repair and anti-inflammatory response. This potential should be further explored in larger studies.

Total Knee Arthroplasty for the Oldest Old.

The present study describes and compares the early functional results after total knee arthroplasty (TKA) of the oldest-old population (aged over 84 years) and a randomly matched younger septuagenarian cohort so treated. We aimed to evaluate the early functional outcomes after patients' rehabilitation and the yearly requirements for hospital readmission and emergency room visits after TKA. We noted a similar length of hospital stay for octogenarian and septuagenarian patients, and we determined that both groups of patients were improving ROM (both flexion and extension) after the rehabilitation program (p < 0.05, in all cases), but there were no significant differences between octogenarian and septuagenarian improvement of the knee function (p > 0.05, in all cases). Patients from both age groups behaved similarly in terms of mobility before starting rehabilitation and after completion of the rehabilitation program. We noted that older octogenarian patients showed a higher one-year hospital readmission rate than younger septuagenarian patients, but similar early emergency room visits for both age groups. The findings of this study allow us to conclude that advanced age in itself should not be a contraindication for TKA.

Functional Status Geriatric Scores: Single-Handed Tools for 30-Day Mortality Risk After Hip Fracture.

BACKGROUND: The 30-day mortality rate after hip fracture surgery has been considered as an indirect indicator of the quality of care. This work aims to appraise the Barthel Index, Katz Index, Lawton-Brody Index, and Physical Red Cross Scale registered in the Comprehensive Geriatric Assessment at admission on the of 30-day death probability after hip fracture surgery. METHODS: Prospective study including 899 hip fracture patients over 65. Bed-ridden, non-surgically treated patients, and high energy trauma or tumoral etiology fractures were excluded. Variables distribution were assessed by χ2, U-Mann Whitney and we performed binary logistic regression and equal tailed Jeffreys 95% CI for risk assessment. P<0.05 was considered statistically significant. RESULTS: We noted a 30-day mortality rate of 5.9%. We related Barthel Index (OR=0.986 [0.975-0.996], p=0.010), Katz Index (OR=1.254 [1.089-1.444], p=0.002), Lawton-Brody Index (OR=0.885 [0.788-0.992], p=0.037), and Physical Red Cross Scale (OR=1.483 [1.094-2.011], p=0.011) with the 30-day mortality of patients after hip fracture surgery. We also validated the Barthel Index inflection point (0-55) (ORBI(0-55)=2.428 [1.379-4.275], p=0.002) and Katz Index inflection point (A-B) (ORKI(A-B)=0.493 [0.273-0.891], p=0.019) for the assessment of the highest risked patients. CONCLUSION: The geriatric functional status scores would be useful multifunctional and standalone tools in the assessment of hip fracture patients as singly predictors of 30-day mortality.

30-day mortality after hip fracture surgery: Influence of postoperative factors.

PURPOSE: The 30-day mortality rate after hip fracture surgery has been considered as an indirect indicator of the quality of care. The aim of this work is to analyse preoperative and postoperative factors potentially related to early 30-day mortality in patients over 65 undergoing hip fracture surgery. METHODS: Prospective cohort study including all consecutive primary hip fracture patients over 65 admitted to Trauma and Orthopaedics department from January 1, 2018 to December 31, 2019. Bed-ridden, non- surgically treated patients, and high energy trauma or tumoral aetiology fractures were excluded. A total of 943 patients were eligible (attrition rate: 2.1%). Follow-up included 30-days after discharge. We noted the 30-day mortality after hip fracture surgery, analysing 130 potentially related variables including biodemographic, fracture-related, preoperative, and postoperative clinical factors. Qualitative variables were assessed by χ2, and quantitative variables by non-parametric tests. Odds ratio determined by binary logistic regression. We selected preventable candidate variables for multivariate risk assessment by logistic regression. RESULTS: A total of 923 patients were enrolled (mean age 86.22±6.8, 72.9% women). The 30-day mortality rate was 6.0%. We noted significant increased mortality on men (OR = 2.381[1.371-4.136], p = 0.002), ageing patients (ORyear = 1.073[1.025-1.122], p = 0.002), and longer time to surgery (ORday = 1.183[1.039-1146], p<0.001), on other 20 preoperative clinical variables, like lymphopenia (lymphocyte count <103/µl, OR = 1.842[1.063-3.191], p = 0.029), hypoalbuminemia (≤3.5g/dl, OR = 2.474[1.316-4.643], p = 0.005), and oral anticoagulant intake (OR = 2.499[1.415-4.415], p = 0.002), and on 25 postoperative clinical variables, like arrhythmia (OR = 13.937[6.263-31.017], p<0.001), respiratory insufficiency (OR = 7.002[3.947-12.419], p<0.001), hyperkalaemia (OR = 10.378[3.909-27.555], p<0.001), nutritional supply requirement (OR = 3.576[1.894-6.752], p = 0.021), or early arthroplasty dislocation (OR = 6.557[1.206-35.640], p = 0.029). We developed a predictive model for early mortality after hip fracture surgery based on postoperative factors with 96.0% sensitivity and 60.7% specificity (AUC = 0.863). CONCLUSION: We revealed that not only preoperative, but also postoperative factors have a great impact after hip fracture surgery. The influence of post-operative factors on 30-day mortality has a logical basis, albeit so far they have not been identified or quantified before. Our results provide an advantageous picture of the 30-day mortality after hip fracture surgery.

Effect of pharmacological treatment prior to admission on the outcome of older hip fracture patients.

PURPOSE: We aim to relate the pharmacological treatment at admission of hip fracture patients with their prognosis. METHODS: We designed a prospective study including 436 hip fracture patients. We classified all the pharmacological treatment prior to admission of each patient into 25 groups according to their active agent and indications. We followed-up patients for one year for survival, emergency department visits (EDV), and in-hospital re-admissions (RAD). Differential analysis was performed by chi-square test, U-Mann Whitney test, and logistic regression. In all cases, p ≤ 0.05 was considered statistically significant. RESULTS: At 30-day follow-up, 14.9% patients noted EDV, 9.2% RAD, and 3.2% dead. Patients taking beta-blockers (p = 0.046), loop diuretics (p = 0.018) or antiparkinsonian (p = 0.009) showed an increased 30-day EDV; patients taking benzodiazepines (p = 0.014), loop diuretics (p = 0.009) or antiparkinsonian (p = 0.009), an increased 30-day RAD. At one-year follow-up, 50.7% patients noted EDV, 30.7% RAD, and 22.7% dead. Patients taking oral antidiabetics (p = 0.006) noted a greater one-year EDV; patients taking major opioids (p = 0.001), benzodiazepines (p = 0.016), cardiac agents (p = 0.046), loop diuretics (p = 0.042), beta-blockers (p = 0.018), oral anticoagulants (p = 0.013) or gastric prophylaxis (p = 0.020), greater RAD; patients taking cardiac agents (p = 0.024), loop diuretics (p = 0.006) or oral anticoagulants (p = 0.015), increased 1-year mortality rate. CONCLUSIONS: The pharmacological treatment noted at admission for hip fracture patients is related to the outcome, in a dose-independent way. The pharmacological treatment could be an additional parameter that could help us to improve the decision-making process and the resource assignation of hip fracture patients. A proper medication review upon admission because of a hip fracture is warranted.

Phase II multicenter randomized controlled clinical trial on the efficacy of intra-articular injection of autologous bone marrow mesenchymal stem cells with platelet rich plasma for the treatment of knee osteoarthritis.

BACKGROUND: Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100 × 106 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF®) as adjuvant in a randomized clinical trial. METHODS: A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF® or intraarticular administration of 100 × 106 cultured autologous BM-MSCs plus PRGF®. Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. RESULTS: No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF® and BM-MSC with PRGF® went from 5 (1.8) to 4.5 (2.2) (p = 0.389) and from 5.3 (1.9) to 3.5 (2.5) (p = 0.01), respectively at 12 months. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF® was 31.9 (16.2) and 22.3 (15.8) respectively (p = 0.002) while that for patients treated with BM-MSC plus PRGF® was 33.4 (18.7) and 23.0 (16.6) (p = 0.053). Although statistical significances between groups have been not detected, only patients being treated with BM-MSC plus PRGF® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage. CONCLUSIONS: Treatment with BM-MSC associated with PRGF® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy. Trial registration Clinical Trials.gov identifier NCT02365142. Nº EudraCT: 2011-006036-23.

The impact of antithrombotic therapy on surgical delay and 2-year mortality in older patients with hip fracture: a prospective observational study.

PURPOSE: To analyze the associations of oral anticoagulant and antiplatelet treatments in older patients requiring surgical treatment for hip fracture with mortality, length of stay, waiting time to surgery and postsurgical immediate complications. METHODS: A prospective observational study, including surgically treated hip fracture patients aged 65 years and older. We analyzed admission status variables, and time to surgery, length of stay and immediate surgical and medical complications. We recorded a 2-year survival follow-up. RESULTS: Of the 237 patients studied, 32.5% received antiplatelet treatment and 17.7% received oral anticoagulant treatment. The overall 2-year mortality was 29.1%. The 2-year mortality rate reached the 33.8% for antiplatelet-treated patients (n.s.) and 45.2% for oral anticoagulated patients (p = 0.011). The length of stay increased significantly associated with the oral anticoagulant or high-dose antiplatelet treatment (p < 0.001). The same happened for the time to surgery (p < 0.001), but no delay was observed for patients with low-dose antiplatelet treatment. Oral anticoagulated and antiplatelet-treated patients had a higher Charlson comorbidity index (p = 0.004, p = 0.019) and ASA score (p = 0.006, p = 0.011). Those treatments were also associated with a higher rate of some immediate postsurgical medical complications. We found a relationship between low hemoglobin at admission and high-dose antiplatelet treatment (p = 0.044). CONCLUSIONS: Hip fracture patients following previous oral anticoagulant treatment have a higher 2-year mortality rate. The oral anticoagulant or high-dose antiplatelet treatments are significantly associated with an increase in the length of stay, related to time to surgery, but we could not demonstrate an effect on early mortality.