Showing papers by "Hospital General Universitario Gregorio Marañón published in 2009"

Echocardiographic Assessment of Valve Stenosis: EAE/ASE Recommendations for Clinical Practice

Abstract: Abbreviations: AR aortic regurgitation, AS aortic stenosis, AVA aortic valve area, CSA cross sectional area, CWD continuous wave Doppler, D diameter, HOCM hypertrophic obstructive cardiomyopathy, LV left ventricle, LVOT left ventricular outflow tract, MR mitral regurgitation, MS mitral stenosis, MVA mitral valve area, DP pressure gradient, RV right ventricle, RVOT right ventricular outflow tract, SV stroke volume, TEE transesophageal echocardiography, T1/2 pressure half-time, TR tricuspid regurgitation, TS tricuspid stenosis, V velocity, VSD ventricular septal defect, VTI velocity time integral

Common variants conferring risk of schizophrenia

Abstract: Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.

Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice

Abstract: AR = aortic regurgitation AS = aortic stenosis AVA = aortic valve area CSA = cross sectional area CWD = continuous wave Doppler D = diameter HOCM = hypertrophic obstructive cardiomyopathy LV = left ventricle LVOT = left ventricular outflow tract MR = mitral regurgitation MS = mitral stenosis MVA = mitral valve area ΔP = pressure gradient RV = right ventricle RVOT = right ventricular outflow tract SV = stroke volume TEE = transesophageal echocardiography T 1/2 = pressure half-time TR = tricuspid regurgitation TS = tricuspid stenosis V = velocity VSD = ventricular septal defect VTI =velocity time integral Valve stenosis is a common heart disorder and an important cause of cardiovascular morbidity and mortality. Echocardiography has become the key tool for the diagnosis and evaluation of valve disease, and is the primary non-invasive imaging method for valve stenosis assessment. Clinical decision-making is based on echocardiographic assessment of the severity of valve stenosis, so it is essential that standards be adopted to maintain accuracy and consistency across echocardiographic laboratories when assessing and reporting valve stenosis. The aim of this paper was to detail the recommended approach to the echocardiographic evaluation of valve stenosis, including recommendations for specific measures of stenosis severity, details of data acquisition and measurement, and grading of severity. These recommendations are based on the scientific literature and on the consensus of a panel of experts. This document discusses a number of proposed methods for evaluation of stenosis severity. On the basis of a comprehensive literature review and expert consensus, these methods were categorized for clinical practice as:

Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza.

Abstract: Introduction Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic

Folate Receptor β Is Expressed by Tumor-Associated Macrophages and Constitutes a Marker for M2 Anti-inflammatory/Regulatory Macrophages

Abstract: Macrophage activation comprises a continuum of functional states critically determined by cytokine microenvironment. Activated macrophages have been functionally grouped according to their response to pro-Th1/proinflammatory stimuli [lipopolysaccharide, IFNγ, granulocyte macrophage colony-stimulating factor (GM-CSF); M1] or pro-Th2/anti-inflammatory stimuli [interleukin (IL)-4, IL-10, M-CSF; M2]. We report that folate receptor β (FRβ), encoded by the FOLR2 gene, is a marker for macrophages generated in the presence of M-CSF (M2), but not GM-CSF (M1), and whose expression correlates with increased folate uptake ability. The acquisition of folate uptake ability by macrophages is promoted by M-CSF, maintained by IL-4, prevented by GM-CSF, and reduced by IFNγ, indicating a link between FRβ expression and M2 polarization. In agreement with in vitro data, FRβ expression is detected in tumor-associated macrophages (TAM), which exhibit an M2-like functional profile and exert potent immunosuppressive functions within the tumor environment. FRβ is expressed, and mediates folate uptake, by CD163+ CD68+ CD14+ IL-10–producing TAM, and its expression is induced by tumor-derived ascitic fluid and conditioned medium from fibroblasts and tumor cell lines in an M-CSF–dependent manner. These results establish FRβ as a marker for M2 regulatory macrophage polarization and indicate that folate conjugates of therapeutic drugs are a potential immunotherapy tool to target TAM. [Cancer Res 2009;69(24):9395–403]

Tuberculosis in Solid-Organ Transplant Recipients: Consensus Statement of the Group for the Study of Infection in Transplant Recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology

Abstract: Tuberculosis is a particularly important condition in solid-organ transplant recipients because of the delay in treatment caused by the difficulties involved in its diagnosis and because of the pharmacological toxicity associated with this treatment. Both treatment delay and toxicity are responsible for the many clinical complications of and high mortality associated with tuberculosis in this population. The Consensus Statement from the Spanish Group for the Study of Infectious Diseases in Transplant Recipients defines the indications for treatment of latent tuberculosis infection in solid-organ transplant recipients, especially in patients with a high risk of pharmacological toxicity, as is the case with liver recipients. We established a series of recommendations regarding the types of drugs and the duration of treatment of tuberculosis in solid-organ recipients, giving special attention to pharmacological interactions between rifampin and immunosuppressive drugs (cyclosporine, tacrolimus, rapamycin, and corticosteroids).

An intervention integrated into daily clinical practice reduces the incidence of delirium during hospitalization in elderly patients.

Abstract: OBJECTIVES: To analyze the effectiveness of a multicomponent intervention integrated into daily practice for the prevention of in-hospital delirium in elderly patients. DESIGN: Controlled study comparing an intervention in a geriatric unit (GI) with usual care in two internal medicine services (UC). SETTING: University hospital in Madrid, Spain. PARTICIPANTS: Five hundred forty-two consecutive patients (170 GI, 372 UC), aged 70 and older, with any of the risk criteria for delirium (cognitive impairment, visual impairment, acute disease severity, dehydration). INTERVENTION: Educational measures and specific actions in seven risk areas (orientation, sensory impairment, sleep, mobilization, hydration, nutrition, drug use). Daily monitoring of adherence. MEASUREMENTS: Baseline characteristics, risk factors for delirium, and quality care indicators were analyzed. The primary endpoint was incidence of delirium assessed daily. The secondary endpoint was functional decline, defined as loss of independence in any of the activities of daily living. The intervention effect was evaluated using logistic regression analysis. RESULTS: Delirium affected 11.7% of the GI group and 18.5% of the UC group (P 5.04). After adjustment for confounders, the intervention was associated with lower incidence of delirium (odds ratio 50.4, 95% confidence interval 50.24‐0.77; P 5.005). In the patients who experienced delirium, severity, length, and recurrence of episodes were similar in both groups. Adherence to the intervention protocols was 75.7%. The intervention reduced the rate of functional decline (45.5% in GI vs 56.3% in UC, P 5.03) and improved other quality indicators (e.g., mobilization and physical restraints reduction). CONCLUSION: A multicomponent, nonpharmacological intervention integrated into routine practice reduces delirium during hospitalization in older patients, improves quality of care, and can be implemented without additional resources in a public healthcare system. J Am Geriatr Soc 57:2029–2036, 2009.

Epidemiology and outcome of Scedosporium prolificans infection, a review of 162 cases.

Abstract: Scedosporium prolificans is a truly emerging fungal pathogen. It has only been recognized as a human pathogen for 22 years and has been related with numerous infections in immunocompromised and immunocompetent patients. A search for cases in the literature was performed and a database was constructed. Cases were reviewed in order to analyse the epidemiology and outcome of infection. A total of 162 cases were included. The median age of patients was 45 years (ranging from a few months to 81 years), and 102 (63%) infections were diagnosed in males. Risk factors for scedosporiosis were malignancy, 74/162 (45.7%), cystic fibrosis, 19/172 (11.7%), and solid organ transplantation 14/162 (8.6%). The most common clinical presentations were disseminated infection, 72/162 cases (44.4%), pulmonary mycosis, 47/162 (29%), and bone and joint infections, 17/162 (10.4%). All disseminated infections afflicted patents with underlying diseases, primarily haematological malignancies (57/72 [80%]). Blood cultures were positive in 70% of patients suffering from disseminated mycosis. Neutropenia, fever and cerebral symptoms were independently related to the development of disseminated infection whereas recovery from aplasia was associated with a reduced risk. The overall mortality was 46.9% but mortality rate was 87.5% in patients with disseminated disease. Survival was independently associated with surgical excision and recovery from aplasia. Antifungal treatments were not related to a reduced risk of death. Infections caused by S. prolificans are life threatening in susceptible patients, and can be considered a truly emerging disease. Infections are difficult to treat since it is a multi-resistant species. Multicenter studies are essential with the aim of developing and disseminating appropriate techniques and protocols to treat this mycosis.

The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors.

Abstract: In order to identify genetic factors related to thyroid cancer susceptibility, we adopted a candidate gene approach. We studied tag- and putative functional SNPs in genes involved in thyroid cell differentiation and proliferation, and in genes found to be differentially expressed in thyroid carcinoma. A total of 768 SNPs in 97 genes were genotyped in a Spanish series of 615 cases and 525 controls, the former comprising the largest collection of patients with this pathology from a single population studied to date. SNPs in an LD block spanning the entire FOXE1 gene showed the strongest evidence of association with papillary thyroid carcinoma susceptibility. This association was validated in a second stage of the study that included an independent Italian series of 482 patients and 532 controls. The strongest association results were observed for rs1867277 (OR[per-allele] = 1.49; 95%CI = 1.30-1.70; P = 5.9x10(-9)). Functional assays of rs1867277 (NM_004473.3:c.-283G>A) within the FOXE1 5' UTR suggested that this variant affects FOXE1 transcription. DNA-binding assays demonstrated that, exclusively, the sequence containing the A allele recruited the USF1/USF2 transcription factors, while both alleles formed a complex in which DREAM/CREB/alphaCREM participated. Transfection studies showed an allele-dependent transcriptional regulation of FOXE1. We propose a FOXE1 regulation model dependent on the rs1867277 genotype, indicating that this SNP is a causal variant in thyroid cancer susceptibility. Our results constitute the first functional explanation for an association identified by a GWAS and thereby elucidate a mechanism of thyroid cancer susceptibility. They also attest to the efficacy of candidate gene approaches in the GWAS era.

The Spanish HIV BioBank: a model of cooperative HIV research.

Abstract: Background: The collection of samples from HIV-infected patients is the beginning of the chain of translational research. To carry out quality research that could eventually end in a personalized treatment for HIV, it is essential to guarantee the availability, quality and traceability of samples, under a strict system of quality management. Methods: The Spanish HIV BioBank was created with the objectives of processing, storing and providing distinct samples from HIV/AIDS patients, categorized according to strictly defined characteristics, free of charge to research projects. Strict compliance to ethical norms is always guaranteed. Results: At the moment, the HIV BioBank possesses nearly 50,000 vials containing different prospective longitudinal study sample types. More than 1,700 of these samples are now used in 19 national and international research projects. Conclusion: The HIV BioBank represents a novel approach to HIV research that might be of general interest not only for basic and clinical research teams working on HIV, but also for those groups trying to establish large networks focused on research on specific clinical problems. It also represents a model to stimulate cooperative research among large numbers of research groups working as a network on specific clinical problems. The main objective of this article is to show the structure and function of the HIV BioBank that allow it to very efficiently release samples to different research project not only in Spain but also in other countries.

Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients

Abstract: Several cellular and molecular alterations have been described in skeletal and respiratory muscles of patients with chronic obstructive pulmonary disease (COPD), but information on potential abnormalities of mitochondrial function is scarce. The aim of the present study was to investigate mitochondrial function in the vastus lateralis (VL) and external intercostalis (EI) of COPD patients. Biopsies from VL and EI were obtained during surgery for lung cancer in 13 patients with mild to moderate COPD (age 68+/-6 yrs, forced expiratory volume in one second (FEV(1)) 66+/-15% predicted) and 19 control subjects (age 67+/-9 yrs, FEV(1) 95+/-18% pred). State 3 and 4 mitochondrial oxygen consumption (V'(O(2),m)), ATP synthesis, citrate synthase, cytochrome oxidase (COX) and complex I-III activities, as well as reactive oxygen species (ROS) production, were determined. In COPD patients, in both muscles, COX activity (VL: COPD 3.0+/-0.8 versus control 2.0+/-0.8; EI: 3.7+/-1.6 versus 2.4+/-0.9 micromol min(-1) mg(-1)) and ROS production (VL: 1,643+/-290 versus 1,285+/-468; EI: 1,033+/-210 versus 848+/-288 arbitrary units) were increased, whereas state 3 V'(O(2),m) was reduced (VL: 2.9+/-0.3 versus 3.6+/-0.4; EI: 3.6+/-0.3 versus 4.1+/-0.4 mmol min(-1) kg(-1)). Skeletal muscle mitochondria of patients with chronic obstructive pulmonary disease show electron transport chain blockade and excessive production of reactive oxygen species. The concurrent involvement of both vastus lateralis and external intercostalis suggests a systemic (rather than a local) mechanism(s) already occurring in relatively early stages (Global Initiative for Chronic Obstructive Lung Disease stage II) of the disease.

Association between anti–cyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis

Abstract: Objective Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease that may not always be related to the presence of traditional cardiovascular risk factors. The aim of this study was to determine if anti–cyclic citrullinated peptide (anti-CCP) antibodies are associated with cardiovascular disease in patients with RA. Methods Anti-CCP antibodies were determined by enzyme-linked immunosorbent assay in the earliest serum sample available from 937 patients with a diagnosis of RA. We studied the relationship between anti-CCP antibodies with traditional cardiovascular risk factors and cardiovascular events. Results We found positive anti-CCP antibodies (>25 units/ml) in 672 patients (71.7%). There was no association between the anti-CCP antibodies and cardiovascular risk factors such as smoking, hypertension, dyslipidemia, being overweight, or diabetes mellitus. However, patients who had positive anti-CCP antibodies experienced more frequent ischemic heart disease (6.5% versus 2.6%; odds ratio [OR] 2.58, 95% confidence interval [95% CI] 1.17–5.65) and had higher mortality rates (11.2% versus 6.8%; OR 1.72, 95% CI 1.01–2.91). Similar results were obtained when we considered anti-CCP titers 20-fold higher (>500 units/ml). Multivariable analysis showed that ischemic heart disease is independently associated with positive anti-CCP antibodies (OR 2.8, 95% CI 1.19–6.56; P = 0.009). Conclusion Anti-CCP antibodies in patients with RA are independently associated with the development of ischemic heart disease.

Incidence and risk factors for ventilator-associated pneumonia after major heart surgery

Abstract: Major heart surgery (MHS) patients are a particularly high-risk population for nosocomial infections. Our objective was to identify risk factors for ventilator-associated pneumonia (VAP) in patients undergoing MHS. Prospective study including 1,844 patients operated from 2003 to 2006. Overall 106 patients (140 episodes) developed one or more episodes of VAP (5.7%, 22.2 episodes per 1,000 days of mechanical ventilation). VAP incidence was 45.9% in those patients requiring more than 48 h of MV. Enterobacteriaceae (32.8), Pseudomonas aeruginosa (28.6%) and Staphylococcus aureus (27.1%, of which 65.8% were methicillin resistant) were the principal microorganisms causing VAP. The independent risk factors for VAP were: age >70, perioperative transfusions, days of mechanical ventilation, reintubation, previous cardiac surgery, emergent surgery and intraoperative inotropic support. Median length of stay in the ICU for patients who developed VAP or not was, respectively, 25.5 versus 3 days (P < 0.001), and mortality was, respectively, 45.7 versus 2.8% in both populations (P < 0.001). We developed a predictive preoperative score with a sensitivity of 93% and a specificity of 40%. VAP is common in patients undergoing MHS that require more than 48 h of MV. In that “high-risk” population, innovative preventive measures should be developed and applied.

Skin testing and drug provocation in the diagnosis of nonimmediate reactions to aminopenicillins in children.

Abstract: Background: Nonimmediate allergic reactions (NIR) to aminopenicillin include several entities, the most common of which are urticaria-like and maculopapular exanthemas. Aims of the study: To evaluate a group of children who developed one or more episodes of skin reactions suggestive of NIR after aminopenicillin administration. Methods: The inclusion criteria required negative immediate skin tests and absence of specific IgE antibodies to different penicillins. Intradermal and patch tests were carried out with delayed readings and, if negative, a drug-provocation test including a full therapeutic course of the drug was given. Two different groups were compared: A) children with positive skin testing or a positive drug-provocation test and B) children with negative skin testing and good tolerance after a drug-provocation test. Results: Group A was composed of 20 patients. Positive intradermal/patch tests were found in one patient and in the remaining 19, a positive response to a drug-provocation test confirmed the diagnosis. Group B (the control group) consisted of 19 patients with similar symptoms after aminopenicillin intake but good tolerance. No differences in age, dose or number of previous treatments were observed between the groups. The clinical entities were also similar in both groups. Conclusions: Reproducible nonimmediate skin reactions to aminopenicillins may occur in children in spite of negative skin testing. The value of this diagnostic procedure seems to be limited in this type of reaction, with drug-provocation tests (DPT) being a reasonable and safe alternative if the diagnosis has to be confirmed.

Risk Factors, Clinical Features, and Outcomes of Listeriosis in Solid-Organ Transplant Recipients: A Matched Case-Control Study

Abstract: Background Solid-organ transplant (SOT) recipients are classically considered to be at increased risk for listeriosis. However, risk factors for this infection have not been assessed. Methods We carried out a multicenter, matched case-control study (1:2 ratio) from January 1995 through December 2007. Control subjects were matched for center, transplant type, and timing. Conditional logistic regression was performed to identify independent risk factors. Clinical features and outcomes for all case patients were reviewed. Results Thirty patients (0.12%) with cases of listeriosis were identified among 25,997 SOT recipients at 15 Spanish transplant centers. In a comparison of case patients with 60 matched control subjects, the following independent risk factors for listeriosis were identified: diabetes mellitus (odds ratio [OR], 5.6; 95% confidence interval [CI], 1.6-19.6; ), P = .007 history of cytomegalovirus infection or disease within the preceding 6 months (OR, 35.9; 95% CI, 2.1-620; P = .014), receipt of high-dose prednisone within the preceding 6 months (OR, 6.2; 95% CI, 1.8-21.1; P = .003), and trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis (OR, 0.07; 95% CI, 0.006-0.76; P = .029). Twenty-six patients (86.7%) had bacteremia, and 7 had shock at presentation. Other manifestations included meningoencephalitis (10 cases), spontaneous peritonitis (2), pleural empyema (1), brain abscesses (1), and liver abscesses (1). The 30-day mortality rate was 26.7% (8 of 30 patients died). Conclusions Listeriosis in SOT recipients is uncommon but causes high mortality. Diabetes mellitus, cytomegalovirus infection or disease, and receipt of high-dose steroids are independent risk factors for this infection, whereas TMP-SMZ prophylaxis is a protective factor.

European consensus statement on the terminology used in the management of lupus glomerulonephritis

Abstract: Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disorder, which often involves referral to multiple medical specialists. Lupus nephritis (LN) occurs in ~35% of adults with SLE and predicts poor survival. There is currently no consensus on how to manage patients with SLE or LN across specialties and across different European countries. The Lupus Nephritis Terminology Advisory Group was formed to address this issue as it impacts upon LN treatment. It has developed consensus statements based on opinions from expert panel meetings with nephrologists, nephropathologists, rheumatologists, clinical immunologists and internal medicine specialists from many European countries, after reviewing current guidelines from the European League Against Rheumatism, the American College of Rheumatology and the participants' experience. In this article, we report consensus statements that were developed in six important areas: classification of patients with LN, how classification affects the selection of treatment options and definitions of induction, response, flare and maintenance. We have also proposed a consensus for the terminology involved in the management of LN that is consistent with clinical opinion gathered from multidisciplinary expert meetings and with existing guidelines. We believe this consensus approach provides agreed expert opinion to clinicians and will form the basis for optimising LN treatment.

Sonographic measurement of cross‐sectional area of the median nerve in the diagnosis of carpal tunnel syndrome: Correlation with nerve conduction studies

Abstract: Purpose. To assess the usefulness of sonographic measurement of the median nerve cross-sectional area (CSA) in the diagnosis of carpal tunnel syndrome (CTS) and grading of its severity using nerve conduction (NC) studies as the standard. Method. The CSA of the median nerve was measured at the tunnel inlet and outlet using the ellipse formula and automatic tracing in 72 hands with suspicion of CTS. Result. The lack of inter-reader reliability led to excluding CSA measurements obtained at the tunnel outlet. Based on the receiver operating characteristic curves, the following cut-off points for the CSA of the median nerve at the tunnel inlet was selected: 9.8 mm and 12.3 mm2 for the ellipse formula and 11 and 13 mm2 for automatic tracing. For the ellipse formula, a CSA less than or equal to 9.8 mm2 excluded CTS whereas a CSA greater than or equal to 12.3 mm2 was diagnostic of CTS with measurements between 9.8 and 12.3 mm2 being indeterminate and requiring NC studies. For automatic tracing, the cutoff value of 11 mm2 was excluded because of the high percentage of false negatives, whereas CSAs greater than or equal to 13 mm2 were diagnostic of CTS. There were no statistically significant differences in CSA measurements between the various degrees of CTS severity determined by NC studies. Conclusion. Sonographic measurement of median nerve CSA at the tunnel inlet is a good alternative to NC studies as the initial diagnostic test for CTS, but it cannot grade the severity of CTS as well as NC studies. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound 2009

Heterogeneous Vancomycin-Intermediate Susceptibility Phenotype in Bloodstream Methicillin-Resistant Staphylococcus aureus Isolates from an International Cohort of Patients with Infective Endocarditis: Prevalence, Genotype, and Clinical Significance

Abstract: Background The significance of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) is unknown. Using a multinational collection of isolates from methicillin-resistant S. aureus (MRSA) infective endocarditis (IE), we characterized IE patients with and without hVISA, and genotyped the infecting strains.

Moesin is required for HIV-1-induced CD4-CXCR4 interaction, F-actin redistribution, membrane fusion and viral infection in lymphocytes.

Abstract: The human immunodeficiency virus 1 (HIV-1) envelope regulates the initial attachment of viral particles to target cells through its association with CD4 and either CXCR4 or CCR5. Although F-actin is required for CD4 and CXCR4 redistribution, little is known about the molecular mechanisms underlying this fundamental process in HIV infection. Using CD4(+) CXCR4(+) permissive human leukemic CEM T cells and primary lymphocytes, we have investigated whether HIV-1 Env might promote viral entry and infection by activating ERM (ezrin-radixin-moesin) proteins to regulate F-actin reorganization and CD4/CXCR4 co-clustering. The interaction of the X4-tropic protein HIV-1 gp120 with CD4 augments ezrin and moesin phosphorylation in human permissive T cells, thereby regulating ezrin-moesin activation. Moreover, the association and clustering of CD4-CXCR4 induced by HIV-1 gp120 requires moesin-mediated anchoring of actin in the plasma membrane. Suppression of moesin expression with dominant-negative N-moesin or specific moesin silencing impedes reorganization of F-actin and HIV-1 entry and infection mediated by the HIV-1 envelope protein complex. Therefore, we propose that activated moesin promotes F-actin redistribution and CD4-CXCR4 clustering and is also required for efficient X4-tropic HIV-1 infection in permissive lymphocytes.