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Lopez-Collazo E.,La Paz University Hospital | del Fresno C.,National Health Research Institute
Critical Care | Year: 2013

Endotoxin tolerance was first described in a study that exposed animals to a sublethal dose of bacterial endotoxin. The animals subsequently survived a lethal injection of endotoxin. This refractory state is associated with the innate immune system and, in particular, with monocytes and macrophages, which act as the main participants. Several mechanisms are involved in the control of endotoxin tolerance; however, a full understanding of this phenomenon remains elusive. A number of recent reports indicate that clinical examples of endotoxin tolerance include not only sepsis but also diseases such as cystic fibrosis and acute coronary syndrome. In these pathologies, the risk of new infections correlates with a refractory state. This review integrates the molecular basis and clinical implications of endotoxin tolerance in various pathologies. © 2013 BioMed Central Ltd.


Liddle A.D.,University of Oxford | Rodriguez-Merchan E.C.,La Paz University Hospital
American Journal of Sports Medicine | Year: 2015

Background: Patellar tendinopathy (PT) is a major cause of morbidity in both high-level and recreational athletes. While there is good evidence for the effectiveness of eccentric exercise regimens in its treatment, a large proportion of patients have disease that is refractory to such treatments. This has led to the development of novel techniques, including platelet-rich plasma (PRP) injection, which aims to stimulate a normal healing response within the abnormal patellar tendon. However, little evidence exists at present to support its use. Purpose: To determine the safety and effectiveness of PRP in the treatment of PT and to quantify its effectiveness relative to other therapies for PT. Study Design: Systematic review. Methods: A systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A literature review was conducted of the Medline, EMBASE, and Cochrane databases as well as trial registries. Both single-arm and comparative studies were included. The outcomes of interest were pain (as measured by visual analog or other, comparable scoring systems), functional scores, and return to sport. Study quality and risk of bias were assessed using the methodological index for nonrandomized studies (MINORS) score and the Cochrane risk of bias tool. Results: Eleven studies fit the inclusion criteria. Of these, 2 were randomized, controlled trials (RCTs), and 1 was a prospective, nonrandomized cohort study. The remainder were single-arm case series. All noncomparative studies demonstrated a significant improvement in pain and function after PRP injection. Complications and adverse outcomes were rare. The results of the comparative studies were inconsistent, and superiority of PRP over control treatments could not be conclusively demonstrated. Conclusion: Platelet-rich plasma is a safe and promising therapy in the treatment of recalcitrant PT. However, its superiority over other treatments such as physical therapy remains unproven. Further RCTs are required to determine the relative effectiveness of the many available treatments for PT and to determine the subgroups of patients who stand to gain the most from the use of these therapies. © 2015 The Author(s).


Rodriguez-Merchan E.C.,La Paz University Hospital
Blood Coagulation and Fibrinolysis | Year: 2012

Fibrin glue and chitosan-based dressings (CBDs) could be useful local haemostatic agents for severe haemorrhage in persons with haemophilia undergoing surgical procedures. The aim of the present study was to clarify the role of fibrin glue and CBDs in persons with haemophilia. A review of the most recent literature on the topic was performed. Local fibrin glue and CBDs are not always necessary to achieve haemostasis in all surgical procedures performed in persons with haemophilia. However, they could be good adjunct therapies, mainly when a surgical field or a surgical wound potentially will bleed more than expected (i.e. patients with inhibitors), and also circumcisions, dental extractions, and some orthopaedic procedures (mainly the surgical removal of pseudotumours). Although a correct surgical haemostasis can be usually achieved by the infusion of factor concentrate at the right dose, my recommendation for surgeons is always to have fibrin glue and CBDs by their side. CBDs could be better haemostatic dressings for control of haemorrhage than current standards of care. To clarify the real value of fibrin glue and CBDs in surgery of haemophilia in specific situations new well designed prospective comparative studies should be carried out. © 2012 Wolters Kluwer Health.


Rodriguez-Merchan E.C.,La Paz University Hospital
Rheumatology International | Year: 2013

Cartilage therapy for focal articular lesions of the knee has been implemented for more than a decade, and it is becoming increasingly available. What do we know on the healing response of cartilage lesions? What do we know on the treatment of focal cartilage lesions of the knee and the prognostic factors involved? PubMed articles related to articular cartilage regeneration of the knee in clinical studies were searched from January 2006 to November 2012, using the following key words: articular cartilage, regeneration, clinical studies, and knee. A total of 44 reports were found. They showed the following possibilities for the treatment of focal lesions of the articular cartilage of the knee: cartilage regeneration and repair including cartilage reparation with gene-activated matrices, autologous chondrocyte implantation (ACI) and matrix-induced ACI (MACI), microfracture, osteochondral autograft transfer (mosaicplasty), biological approaches (scaffolds, mesenchymal stem cells - MSCs, platelet-rich plasma, growing factors - GF, bone morphogenetic proteins - BMPs, magnetically labeled synovium-derived cells - M-SDCs, and elastic-like polypeptide gels), osteotomies, stem-cell-coated titanium implants, and chondroprotection with pulsed electromagnetic fields. Untreated cartilage lesions on the femoral condyles had a superior healing response compared to those on the tibial plateaus, and in the patellofemoral joint. Clinical outcome regarding the treatment of medial defects is better than that of the lateral defects. Improvement from baseline was better for patients < or = 30 years compared with patients > or = 30 years. ACI, MACI, and mosaicplasty have shown similar results. The results of comparative clinical studies using ACI have shown some superiority over conventional microfracturing in medium or large defects and in long-term durability. Some biological methods such as scaffolds, MSCs, GF, M-SDCs, BMPs, and elastic-like polypeptide gels still need more research. © Springer-Verlag Berlin Heidelberg 2012.


Rodriguez-Merchan E.C.,La Paz University Hospital
HSS Journal | Year: 2011

Background Knee prosthesis instability (KPI) is a frequent cause of failure of total knee arthroplasty. Moreover, the degree of constraint required to achieve immediate and long-term stability in total knee arthroplasty (TKA) is frequently debated. Questions This review aims to define the problem, analyze risk factors, and review strategies for prevention and treatment of KPI. Methods A PubMed (MEDLINE) search of the years 2000 to 2010 was performed using two key words: TKA and instability. One hundred and sixty-five initial articles were identified. The most important (17) articles as judged by the author were selected for this review. The main criteria for selection were that the articles addressed and provided solutions to the diagnosis and treatment of KPI. Results Patient-related risk factors predisposing to post-operative instability include deformity requiring a large surgical correction and aggressive ligament release, general or regional neuromuscular pathology, and hip or foot deformities. KPI can be prevented in most cases with appropriate selection of implants and good surgical technique. When ligament instability is anticipated post-operatively, the need for implants with a greater degree of constraint should be anticipated. In patients without significant varus or valgus malalignment and without significant flexion contracture, the posterior cruciate ligament (PCL) can be retained. However, the PCL should be sacrificed when deformity exists particularly in patients with rheumatoid arthritis, previous patellectomy, previous high tibial osteotomy or distal femoral osteotomy, and posttraumatic osteoarthritis with disruption of the PCL. In most cases, KPI requires revision surgery. Successful outcomes can only be obtained if the cause of KPI is identified and addressed. Conclusions Instability following TKA is a common cause of the need for revision. Typically, knees with deformity, rheumatoid arthritis, previous patellectomy or high tibial osteotomy, and posttraumatic arthritis carry higher risks of post-operative instability and are indications for more constrained TKA designs. Instability following TKA usually requires revision surgery which must address the cause of the instability for success. © 2011 Hospital for Special Surgery.


Rodriguez-Merchan E.C.,La Paz University Hospital
Blood Coagulation and Fibrinolysis | Year: 2013

The incidence of bleeding as a result of a pseudoaneurysm in haemophilia is very low. The diagnosis should be suspected if the patient has a history of arterial trauma. Pseudoaneurysms can appear anywhere where trauma occurs. This can include arterial access for catheterization, blunt trauma or penetrating trauma. The diagnosis should be confirmed using Duplex ultrasonography, computed tomography (CT) angiogram or conventional angiogram. Many options exist for the treatment of pseudoaneurysms. Although surgery was the gold standard treatment in the past (surgical ligation with or without distal bypass), several less invasive treatment options are popular today. They include covered stent, ultrasound probe compression and ultrasound-guided thrombin injection. So far, only 14 pseudoaneurysms have been reported in patients with haemophilia: nine were located in the musculoskeletal system (four in the hand, four in the knee, one in the ankle), whereas five were nonmusculoskeletal. Early diagnosis and treatment of this complication is vital. Endovascular treatment offers a minimally invasive treatment option. If arterial embolization fails to solve the pseudoaneurysm, open vascular surgery with surgical ligation with or without distal bypass should be performed. Whatever the procedure, a correct surgical haemostasis must be achieved by the infusion of factor concentrate (recombinant or plasma-derived) at the right dose and tranexamic acid. The advent of activated prothrombin complex concentrates and recombinant factor VIII (rFVIIa) has made invasive procedures possible in haemophilia patients with high-titre inhibitors. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Rodriguez-Merchan E.C.,La Paz University Hospital
Blood Coagulation and Fibrinolysis | Year: 2013

Acute compartment syndrome (ACS) is characterized by an increase in pressure (intramuscular pressure) within a muscle compartment, which reduces capillary perfusion threatening tissue survival. Persistence of this increased pressure for a few hours will result in necrosis of muscle and nerve tissue, with contracture in the affected limb and permanent loss of function. For that reason, early treatment and diagnosis of ACS is fundamental. Diagnosis should be based on physical examination (pain on stretching the involved muscles) and on an objective measurement of the limb perfusion pressure (DBP minus intramuscular pressure) within the affected compartment. To obtain a reliable clinical diagnosis, the patient must be evaluated every 1-2h. In children and in unconscious patients, where the level of pain cannot be appropriately determined, an accurate clinical diagnosis is unfeasible, hence the importance of measuring compartment pressure. A fasciotomy should be performed when the limb perfusion pressure is less than 30mmHg when averaged over a 12-h period (monitored every 1-2h). Only 16 studies have been published on haemophilic patients with ACS, which report on a total of 34 cases. If symptoms or pressure measurements are suggestive of ACS, an extensive fasciotomy will be required. Unfortunately, fasciotomy is not exempt from complications such as the need of subsequent surgery because of a delay in wound healing, the need of a skin graft, pain, cosmetic problems, nerve injury, permanent muscle weakness and chronic venous insufficiency. Overlooked compartment syndrome remains one of most common causes of malpractice lawsuits. In haemophilia, adequate substitution of coagulation factor must be the first step. The main principle of surgical treatment is an extensive fasciotomy. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Pellicer A.,La Paz University Hospital | Bravo M.D.C.,La Paz University Hospital
Seminars in Fetal and Neonatal Medicine | Year: 2011

Near infrared spectroscopy (NIRS) is a light-based technology used to monitor tissue oxygen status. Refinements to the method since it was first described have extended its applicability to different research and clinical settings due to its non-invasiveness, instrument portability and ease of use.Classic NIRS recordings, based in the Beer-Lambert law, can be used for the trend monitoring of changes in tissue perfusion-oxygenation parting from an arbitrary zero point. However, in order to derive intermittently quantitative values in absolute terms, certain manoeuvres must be performed. More recently, the evolution of the technique has led to the development of instruments that provide an absolute value of regional hemoglobin saturation in a continuous manner.This review will focus on the physical principles of tissue spectroscopy including a brief description of the different operating principles that are currently in use or under development. The theoretical details, experimental procedures and data analysis involved in the measurements of physiological variables using NIRS will be described. The future beyond the scope of NIRS and potential lines of research will also be discussed. © 2010 Elsevier Ltd.


Rodriguez-Merchan E.C.,La Paz University Hospital
Archives of Bone and Joint Surgery | Year: 2015

There is controversy in the literature regarding a number of topics related to anterior cruciate ligament (ACL) reconstruction. The purpose of this article is to answer the following questions: 1) Bone-patellar tendon-bone reconstruction (BPTB-R) or hamstrimg reconstruction (H-R); 2) Double bundle or single bundle; 3) Allograft or authograft; 4) Early or late reconstruction; 5) Rate of return to sports after ACL reconstruction; 6) Rate of osteoarthritis after ACL reconstruction. A Cochrane Library and PubMed (MEDLINE) search of systematic reviews and meta-analysis related to ACL reconstruction was performed. The key words were: ACL reconstruction, systematic reviews and meta-analysis. The main criteria for selection were that the articles were systematic reviews and meta-analyses focused on the aforementioned questions. Sixty-nine articles were found, but only 26 were selected and reviewed because they had a high grade (I-II) of evidence. BPTB-R was associated with better postoperative knee stability but with a higher rate of morbidity. However, the results of both procedures in terms of functional outcome in the long-term were similar. The double-bundle ACL reconstruction technique showed better outcomes in rotational laxity, although functional recovery was similar between single-bundle and double-bundle. Autograft yielded better results than allograft. There was no difference between early and delayed reconstruction. 82% of patients were able to return to some kind of sport participation. 28% of patients presented radiological signs of osteoarthritis with a follow-up of minimum 10 years. © 2015 BY THE ARCHIVES OF BONE AND JOINT SURGERY.


Rodriguez-Merchan E.C.,La Paz University Hospital
Archives of Bone and Joint Surgery | Year: 2015

Prosthetic joint infection (PJI) is a serious complication of total knee arthroplasty (TKA). Control of infection after a failed two-stage TKA is not always possible, and the resolution of infection may require an above-knee amputation (AKA) or a the-knee (KF). The purpose of this review is to determine which treatment method (AKA or KF) yields better function and ambulatory status for patients after a failed two-stage reimplantation. A PubMed search related to the resolution of infection by means of an above-the-knee amputation (AKA) or a knee fusion was performed until 10 January 2015. The key words were: infected TKA and above-the-knee amputation. Five hundred and sixty-six papers were found, of which ten were reviewed because they were focused on the topic of the article. KF should be strongly considered as the treatment of choice for patients who have persistent infected TKA after a failed two-stage revision arthroplasty. Patients can walk at least inside the house, and activity of daily living independence is achieved by the patients with successful KF, although walking aids, including a shoe lift, are required. An intramedullary nail leads to better functional results than an external fixator. The functional outcome after AKA performed after TKA is poor. A substantial percentage of the patients never fit with a prosthesis, and those who are seldom obtain functional independence. Only 50% of patients are able to walk after AKA. Patients receiving KF for treating recurrent PJI after TKA have better function and ambulatory status compared to patients receiving AKA. KF must be recommended as the treatment of choice for patients who have persistent infected TKA after a failed two-stage reimplantation procedure. © 2015 BY THE ARCHIVES OF BONE AND JOINT SURGERY.

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