Virus-like particle-mediated delivery of structure-selected neoantigens demonstrates immunogenicity and antitumoral activity in mice.

BACKGROUND: Neoantigens are patient- and tumor-specific peptides that arise from somatic mutations. They stand as promising targets for personalized therapeutic cancer vaccines. The identification process for neoantigens has evolved with the use of next-generation sequencing technologies and bioinformatic tools in tumor genomics. However, in-silico strategies for selecting immunogenic neoantigens still have very low accuracy rates, since they mainly focus on predicting peptide binding to Major Histocompatibility Complex (MHC) molecules, which is key but not the sole determinant for immunogenicity. Moreover, the therapeutic potential of neoantigen-based vaccines may be enhanced using an optimal delivery platform that elicits robust de novo immune responses. METHODS: We developed a novel neoantigen selection pipeline based on existing software combined with a novel prediction method, the Neoantigen Optimization Algorithm (NOAH), which takes into account structural features of the peptide/MHC-I interaction, as well as the interaction between the peptide/MHC-I complex and the TCR, in its prediction strategy. Moreover, to maximize neoantigens' therapeutic potential, neoantigen-based vaccines should be manufactured in an optimal delivery platform that elicits robust de novo immune responses and bypasses central and peripheral tolerance. RESULTS: We generated a highly immunogenic vaccine platform based on engineered HIV-1 Gag-based Virus-Like Particles (VLPs) expressing a high copy number of each in silico selected neoantigen. We tested different neoantigen-loaded VLPs (neoVLPs) in a B16-F10 melanoma mouse model to evaluate their capability to generate new immunogenic specificities. NeoVLPs were used in in vivo immunogenicity and tumor challenge experiments. CONCLUSIONS: Our results indicate the relevance of incorporating other immunogenic determinants beyond the binding of neoantigens to MHC-I. Thus, neoVLPs loaded with neoantigens enhancing the interaction with the TCR can promote the generation of de novo antitumor-specific immune responses, resulting in a delay in tumor growth. Vaccination with the neoVLP platform is a robust alternative to current therapeutic vaccine approaches and a promising candidate for future personalized immunotherapy.

Nucleic Acid Vaccines Encoding Proteins and Virus-like Particles for HIV Prevention.

The development of HIV prophylactic vaccines is facing an impasse, since all phase IIb/III clinical trials were halted in 2023 without demonstrating efficacy. Thus, the field is in need of developing novel immunogens and vaccination strategies that induce broadly neutralising antibodies together with potent Fc-dependent effector functions, as well as protective cross-reactive CD4+ and CD8+ T cell responses. Nucleic acid vaccines, particularly mRNA vaccines, have been one of the major groundbreaking advances in the current decade. Nucleic acid vaccines may help recalibrate the HIV vaccine field towards the use of delivery systems that allow the proper expression of immunogens as a sole antigen (i.e., membrane-bound trimeric envelope glycoproteins) or even to be displayed in a multiantigen platform that will be synthesised by the host. In this review, we will summarise how the multiple HIV vaccine strategies pursued in the last 40 years of HIV research have driven current vaccine development, which are the most relevant immunogens identified so far to induce balanced adaptive immune responses, and how they can benefit from the acceptance of nucleic acid vaccines in the market by reducing the limitations of previous delivery systems. The incorporation of nucleic acid vaccines into the current heterogeneous repertoire of vaccine platforms may represent an invaluable opportunity to reignite the fight against HIV.

Production and Immunogenicity of FeLV Gag-Based VLPs Exposing a Stabilized FeLV Envelope Glycoprotein.

The envelope glycoprotein (Env) of retroviruses, such as the Feline leukemia virus (FeLV), is the main target of neutralizing humoral response, and therefore, a promising vaccine candidate, despite its reported poor immunogenicity. The incorporation of mutations that stabilize analogous proteins from other viruses in their prefusion conformation (e.g., HIV Env, SARS-CoV-2 S, or RSV F glycoproteins) has improved their capability to induce neutralizing protective immune responses. Therefore, we have stabilized the FeLV Env protein following a strategy based on the incorporation of a disulfide bond and an Ile/Pro mutation (SOSIP) previously used to generate soluble HIV Env trimers. We have characterized this SOSIP-FeLV Env in its soluble form and as a transmembrane protein present at high density on the surface of FeLV Gag-based VLPs. Furthermore, we have tested its immunogenicity in DNA-immunization assays in C57BL/6 mice. Low anti-FeLV Env responses were detected in SOSIP-FeLV soluble protein-immunized animals; however, unexpectedly no responses were detected in the animals immunized with SOSIP-FeLV Gag-based VLPs. In contrast, high humoral response against FeLV Gag was observed in the animals immunized with control Gag VLPs lacking SOSIP-FeLV Env, while this response was significantly impaired when the VLPs incorporated SOSIP-FeLV Env. Our data suggest that FeLV Env can be stabilized as a soluble protein and can be expressed in high-density VLPs. However, when formulated as a DNA vaccine, SOSIP-FeLV Env remains poorly immunogenic, a limitation that must be overcome to develop an effective FeLV vaccine.

VLPs generated by the fusion of RSV-F or hMPV-F glycoprotein to HIV-Gag show improved immunogenicity and neutralizing response in mice.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccines have been long overdue. Structure-based vaccine design created a new momentum in the last decade, and the first RSV vaccines have finally been approved in older adults and pregnant individuals. These vaccines are based on recombinant stabilized pre-fusion F glycoproteins administered as soluble proteins. Multimeric antigenic display could markedly improve immunogenicity and should be evaluated in the next generations of vaccines. Here we tested a new virus like particles-based vaccine platform which utilizes the direct fusion of an immunogen of interest to the structural human immunodeficient virus (HIV) protein Gag to increase its surface density and immunogenicity. We compared, in mice, the immunogenicity of RSV-F or hMPV-F based immunogens delivered either as soluble proteins or displayed on the surface of our VLPs. VLP associated F-proteins showed better immunogenicity and induced superior neutralizing responses. Moreover, when combining both VLP associated and soluble immunogens in a heterologous regimen, VLP-associated immunogens provided added benefits when administered as the prime immunization.

Production and characterization of novel Anti-HIV Fc-fusion proteins in plant-based systems: Nicotiana benthamiana & tobacco BY-2 cell suspension.

Multifunctional anti-HIV Fc-fusion proteins aim to tackle HIV efficiently through multiple modes of action. Although results have been promising, these recombinant proteins are hard to produce. This study explored the production and characterization of anti-HIV Fc-fusion proteins in plant-based systems, specifically Nicotiana benthamiana plants and tobacco BY-2 cell suspension. Fc-fusion protein expression in plants was optimized by incorporating codon optimization, ER retention signals, and hydrophobin fusion elements. Successful transient protein expression was achieved in N. benthamiana, with notable improvements in expression levels achieved through N-terminal hydrophobin fusion and ER retention signals. Stable expression in tobacco BY-2 resulted in varying accumulation levels being at highest 2.2.mg/g DW. The inclusion of hydrophobin significantly enhanced accumulation, providing potential benefits for downstream processing. Mass spectrometry analysis confirmed the presence of the ER retention signal and of N-glycans. Functional characterization revealed strong binding to CD64 and CD16a receptors, the latter being important for antibody-dependent cellular cytotoxicity (ADCC). Interaction with HIV antigens indicated potential neutralization capabilities. In conclusion, this research highlights the potential of plant-based systems for producing functional anti-HIV Fc-fusion proteins, offering a promising avenue for the development of these novel HIV therapies.

Immune responses associated with mpox viral clearance in men with and without HIV in Spain: a multisite, observational, prospective cohort study.

BACKGROUND: Since the emergence of the global mpox outbreak in May, 2022, more than 90 000 cases have been diagnosed across 110 countries, disproportionately affecting people with HIV. The durability of mpox-specific immunity is unclear and reinfections have been reported. We aimed to compare mpox immune responses up to 6 months after diagnosis in participants with and without HIV and assess their effect on disease severity and viral clearance dynamics. METHODS: This study was embedded within a prospective, observational, multicentre cohort study of viral clearance dynamics among people with mpox in Spain (MoViE). We included women and men aged 18 years or older, who had signs of mpox, and reported having symptom onset within the previous 10 days at the moment of mpox diagnosis from three sex clinics of the Barcelona metropolitan area. Samples from skin ulcers were collected weekly to estimate the time to clear monkeypox virus (MPXV) from skin lesions. Blood samples were taken at diagnosis, 29, 91, and 182 days later for immune analysis. This included quantifying IgG and IgA against three mpox antigens by ELISA, evaluating in-vitro neutralisation, and characterising mpox-specific T-cell responses using interferon γ detecting enzyme-linked immunospot (ELISpot) assay and multiparametric flow cytometry. FINDINGS: Of the 77 originally enrolled participants, we included 33 participants recruited between July 19, and Oct 6, 2022. Participants without HIV (19 [58%] participants) and participants with HIV (14 [42%] participants) had similar clinical severity and time to MPXV clearance in skin lesions. Participants with HIV had a CD4+ T-cell count median of 777 cells per µL (IQR 484-1533), and 11 (78%) of 14 were virally suppressed on antiretroviral therapy. Nine (27%) of 33 participants were age 49 years or older. 15 (45%) of 33 participants were originally from Spain, and all participants were men. Early humoral responses, particularly concentrations and breadth of IgG and IgA, were associated with milder disease and faster viral clearance. Orthopoxvirus-specific T cells count was also positively correlated with MPXV clearance. Antibody titres declined more rapidly in participants with HIV, but T-cell responses against MPXV were sustained up to day 182 after diagnosis, regardless of HIV status. INTERPRETATION: Higher breadth and magnitude of B-cell and T-cell responses are important in facilitating local viral clearance, limiting mpox dissemination, and reducing disease severity in individuals with preserved immune system. Antibodies appear to contribute to early viral control and T-cell responses are sustained over time, which might contribute to milder presentations during reinfection. FUNDING: Fundació Lluita contra les Infeccions, IrsiCaixa, and Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación e Universidades.

Immunisation efficacy of a stabilised SARS-CoV-2 spike glycoprotein in two geriatric animal models.

Age is associated with reduced efficacy of vaccines and linked to higher risk of severe COVID-19. Here we determined the impact of ageing on the efficacy of a SARS-CoV-2 vaccine based on a stabilised Spike glycoprotein (S-29) that had previously shown high efficacy in young animals. Thirteen to 18-month-old golden Syrian hamsters (GSH) and 22-23-month-old K18-hCAE2 mice were immunised twice with S-29 protein in AddaVaxTM adjuvant. GSH were intranasally inoculated with SARS-CoV-2 either two weeks or four months after the booster dose, while all K18-hACE2 mice were intranasally inoculated two weeks after the second immunisation. Body weight and clinical signs were recorded daily post-inoculation. Lesions and viral load were investigated in different target tissues. Immunisation induced seroconversion and production of neutralising antibodies; however, animals were only partially protected from weight loss. We observed a significant reduction in the amount of viral RNA and a faster viral protein clearance in the tissues of immunized animals. Infectious particles showed a faster decay in vaccinated animals while tissue lesion development was not altered. In GSH, the shortest interval between immunisation and inoculation reduced RNA levels in the lungs, while the longest interval was equally effective in reducing RNA in nasal turbinates; viral nucleoprotein amount decreased in both tissues. In mice, immunisation was able to improve the survival of infected animals. Despite the high protection shown in young animals, S-29 efficacy was reduced in the geriatric population. Our research highlights the importance of testing vaccine efficacy in older animals as part of preclinical vaccine evaluation.

Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection.

Safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are crucial to fight against the coronavirus disease 2019 pandemic. Most vaccines are based on a mutated version of the Spike glycoprotein [K986P/V987P (S-2P)] with improved stability, yield and immunogenicity. However, S-2P is still produced at low levels. Here, we describe the V987H mutation that increases by two-fold the production of the recombinant Spike and the exposure of the receptor binding domain (RBD). S-V987H immunogenicity is similar to S-2P in mice and golden Syrian hamsters (GSH), and superior to a monomeric RBD. S-V987H immunization confer full protection against severe disease in K18-hACE2 mice and GSH upon SARS-CoV-2 challenge (D614G or B.1.351 variants). Furthermore, S-V987H immunized K18-hACE2 mice show a faster tissue viral clearance than RBD- or S-2P-vaccinated animals challenged with D614G, B.1.351 or Omicron BQ1.1 variants. Thus, S-V987H protein might be considered for future SARS-CoV-2 vaccines development.

Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant.

Most COVID-19 vaccines are based on the SARS-CoV-2 Spike glycoprotein (S) or their subunits. However, S shows some structural instability that limits its immunogenicity and production, hampering the development of recombinant S-based vaccines. The introduction of the K986P and V987P (S-2P) mutations increases the production and immunogenicity of the recombinant S trimer, suggesting that these two parameters are related. Nevertheless, S-2P still shows some molecular instability and it is produced with low yield. Here we described a novel set of mutations identified by molecular modeling and located in the S2 region of the S-2P that increase its production up to five-fold. Besides their immunogenicity, the efficacy of two representative S-2P-based mutants, S-29 and S-21, protecting from a heterologous SARS-CoV-2 Beta variant challenge was assayed in K18-hACE2 mice (an animal model of severe SARS-CoV-2 disease) and golden Syrian hamsters (GSH) (a moderate disease model). S-21 induced higher level of WH1 and Delta variants neutralizing antibodies than S-2P in K18-hACE2 mice three days after challenge. Viral load in nasal turbinate and oropharyngeal samples were reduced in S-21 and S-29 vaccinated mice. Despite that, only the S-29 protein protected 100% of K18-hACE2 mice from severe disease. When GSH were analyzed, all immunized animals were protected from disease development irrespectively of the immunogen they received. Therefore, the higher yield of S-29, as well as its improved immunogenicity and efficacy protecting from the highly pathogenic SARS-CoV-2 Beta variant, pinpoint the S-29 mutant as an alternative to the S-2P protein for future SARS-CoV-2 vaccine development.

Disección coronaria espontánea asociada a lupus eritematoso sistémico / Spontaneous coronary dissection associated with systemic lupus erythematosus

Resumen A 29 year old female with a past medical history of systemic lupus erythematosus, diagnosed 15 years earlier, presents with lupus nephritis, currently on peritoneal dialysis. She had myopericarditis in 2012 and is currently on immunosuppressants. The patient began with exertional dyspnea and angina 2 weeks before admission. An echocardiogram was performed, reporting severe mitral and tricuspid insufficiency. Afterwards, the patient presented with resting angina associated with an adrenergic and vagal response. Initially, rheumatology ruled out autoimmune activity caused by lupus. We performed a coronary angiogram based on clinical presentation, EKG changes and biomarkers, finding a trivascular coronary artery disease classified as a Markis I coronary artery ectasia and a coronary dissection of the ramus intermedius and the circumflex, posterior to the first obtuse marginal artery. Cardiothoracic surgery considered intervention with a coronary bridge posterior to the dissection of the intermedius ramus artery, marginal obtuse and posterolateral artery, as well as a mitral valve replacement and a tricuspid valve repair. Coronary dissection is more common in women (70%), clinical presentation varies from unstable angina to sudden death. In lupus nephritis, it is an uncommon form of extra renal vasculitis. Treatment depends on the number of arteries affected, as well as the haemodynamic state of the patient. It is imperative to individualize treatment options.

Abstract Se presenta el caso de una paciente de 29 años con antecedente de lupus eritematoso sistémico diagnosticado 15 años antes, que desarrolló nefropatía lúpica actualmente en diálisis peritoneal, cuadro de miopericarditis en 2012 y bajo tratamiento inmunosupresor. Inició con deterioro de su clase funcional por disnea y angina 2 semanas previas al ingreso. Se le realizó ecocardiograma, el cual reportó insuficiencias mitral y tricuspídea graves. Posteriormente presentó angina en reposo asociada a descarga adrenérgica y vagal. A su ingreso se descarta actividad lúpica por reumatología. Por presentación clínica, cambios en electrocardiograma y biomarcadores, se realizó cateterismo cardiaco, que reportó enfermedad coronaria trivascular con ectasia coronaria Markis I y disección coronaria de ramo intermedio y circunfleja posterior a la primera marginal obtusa. Se consideró por el servicio de cirugía cardiotorácica realizar intervención con puente coronario posterior a disección del ramo intermedio, marginal obtusa y posterolateral, así como cambio valvular mitral y plastia tricuspídea. La disección coronaria espontánea es más frecuente en las mujeres (70%); puede presentarse como angina inestable y hasta como muerte súbita. La asociación con lupus eritematoso sistémico es poco frecuente, con una incidencia del 0.42%. En la nefropatía lúpica es una manifestación poco frecuente de vasculitis extrarrenal. El tratamiento de elección depende del número de vasos afectados y del estado hemodinámico, por lo que es necesario individualizarlo para cada paciente.

Abscesos cerebrales por Nocardia spp. en una paciente inmunocompetente / Multiple brain abscesses due to Nocardia spp. in an immunocompetent patient

La infección por Nocardia spp. no es común en pacientes inmunocompetentes. El tratamiento antimicrobiano empírico dirigido según las regiones anatómicas, no contempla las particularidades del germen y el análisis microbiológico se hace necesario para el tratamiento específico. A continuación, se presenta el caso de una paciente previamente sana, inmunocompetente y sin factores de riesgo conocidos para la infección por Nocardia spp., con evidencia de compromiso en el parénquima pulmonar y la piel, que posteriormente desarrolló varios abscesos cerebrales.

The infection by Nocardia spp is not common in immunocompetent patients. The empirical antimicrobial treatment directed by anatomical regions does not contemplate the particularities of the germ and the microbiological analysis is necessary for the specific treatment. We present the case of a previously healthy and immunocompetent patient, without known risk factors for Nocardia spp. infection, with evidence of involvement of the pulmonary parenchyma and the skin and subsequent development of multiple brain abscesses.

Manifestaciones radiológicas de malformaciones pulmonares congénitas. Experiencia de tres hospitales en Bogotá / Radiological Manifestations of Congenital Lung Malformations. Experience of three Hospitals in Bogotá

Objective: To describe the radiological characteristics of congenital pulmonary and airway malformations which are frequently found in pediatric patients, from three hospitals in Bogotá between the years 2010 - 2016. Materials and methods: Retrospective, observational and descriptive study with a sample of 27 patients, with an average age of 5 months, who met inclusion criteria: patients between 0 months and 17 years of age, with a confirmed diagnosis of congenital malformation of the lung, who underwent surgery for lung or airway lesion and whose histopathological study was compatible with congenital malformation of the lung. Results: The prevalence of congenital malformations is higher in females. 80% of cases had prenatal diagnosis, with cystic adenomatoid malformation being the most common and the main radiological feature being the cyst. Conclusion: Computed tomography allows detailed studies of these malformations, achieving greater accuracy compared to conventional techniques such as chest radiography and ultrasound.

Presentación atípica de la poliangeítis microscópica con compomiso renal, pulmonar, dermatológico y del sistema nervioso central / Atypical presentation of microscopic polyangiitis with renal, pulmonary, dermatological and central nervous system involvement

La poliangeítis microscópica (PAM) es una vasculitis autoinmune caracterizada por la inflamación de los vasos sanguíneos de pequeño calibre y la presencia de anticuerpos anticitoplasma de neutrófilos (ANCA). Clínicamente se caracteriza por presentar glomerulonefritis y capilaritis pulmonar aunque la afectación de la piel, los nervios y el tracto gastrointestinal no es infrecuente. Presentamos el caso de un paciente de 17 años con manifestaciones atípicas dadas por glomerulonefritis pauci-inmune, hemorragia pulmonar, vasculitis leucocitoclásica cutánea y hemorragia cerebral. Además revisamos las características histológicas y radiológicas.

Microscopic polyangiitis (MPA) is an autoimmune antineutrophil cytoplasmic antibody-associated (ANCA) small-vessel vasculitis. It is clinically characterized by glomerulonephritis and pulmonary capillaritis, however, skin, nerve and gastrointestinal tract involvement is also relatively common. A case is presented in a 17-year-old male patient with atypical manifestations, such as, pauci-immune glomerulonephritis, alveolar hemorrhage, cutaneous leukocytoclastic vasculitis and cerebral hemorrhage. MPA histologic and radiologic features were also reviewed.

Tuberculosis in the era of anti-TNF-alpha therapy: Why does the risk still exist? / La tuberculosis en la era del tratamiento con fármacos inhibidores del factor de necrosis tumoral alfa: ¿por qué persiste el riesgo?

Abstract Rheumatoid arthritis is an autoimmune systemic disease characterized mainly by inflammatory compromise of diarthrodial joints. Multiple drug therapies have been developed to control the activity of rheumatoid arthritis, among them, the first line of disease-modifying antirheumatic drugs (DMARD), and novel drug therapies such as the anti-TNF alpha therapy, with satisfactory clinical outcomes. Despite this positive fact, the use of this therapy implies the risk of producing negative effects due to its mechanism of action, which has been associated with multiple infections, especially tuberculosis, making it necessary to use screen tests before resorting to this kind of drugs. We present the case of a 58-year-old female patient, with a six-year history of rheumatoid arthritis. The patient developed disseminated tuberculosis with compatible radiological and histological findings after receiving treatment with infliximab (anti-TNF therapy). No test was performed to screen for latent tuberculosis infection prior to the administration of infliximab. The performance of routine screenings tests for tuberculosis prior to anti-TNF alpha therapy plays an essential role in the detection of asymptomatic patients with latent tuberculosis. This is the only way to identify those patients who would benefit from anti-tuberculosis drugs before the initiation of anti-TNF alpha therapy, which makes the difference in the search of a significant reduction in the incidence of tuberculosis and its associated morbidity and mortality.

Resumen La artritis reumatoidea es una enfermedad crónica de carácter autoinmunitario caracterizada principalmente por el compromiso inflamatorio de las articulaciones cartilaginosas. Se han desarrollado múltiples tratamientos farmacológicos para controlar el avance de la artritis reumatoidea, entre ellos, los fármacos antirreumáticos modificadores de la enfermedad, además de nuevos esquemas terapéuticos con inhibidores del factor de necrosis tumoral alfa, con resultados clínicos satisfactorios. Sin embargo, el uso de tales medicamentos no resulta inocuo, ya que se los ha asociado con diversos efectos secundarios, especialmente, infecciones como la tuberculosis, lo cual exige la aplicación de pruebas de tamización antes de utilizarlos. Se reporta el caso de una paciente de 58 años de edad con artritis reumatoidea de seis años de evolución, que después de recibir tratamiento con uno de estos fármacos, el infliximab, desarrolló tuberculosis diseminada, cuyo diagnóstico se confirmó mediante radiología e histopatología. No se emplearon pruebas de detección de la tuberculosis latente antes de prescribirle el infliximab. Las pruebas de tamización para tuberculosis deben emplearse de forma rutinaria, con el fin de detectar aquellos pacientes con tuberculosis latente, ya que es la única manera de determinar si se requiere profilaxis antituberculosa antes de administrar dichos fármacos, hecho que marca la diferencia cuando se busca disminuir la incidencia de tuberculosis y la consecuente morbimortalidad.

Abscesos hepáticos múltiples y empiema: una presentación inusual de actinomicosis / Multiple hepatic abscesses and empyema: An unusual presentation of actinomycosis

La actinomicosis es una entidad infecciosa causada por bacterias anaerobias del género Actinomyces spp. En general, la actinomicosis presenta un curso clínico larvado que dificulta su diagnóstico. Describimos el caso de un paciente con empiema por Actinomyces spp. secundario a rotura a la cavidad pleural de un absceso hepático.

Actinomycosis is an infectious disease caused by anaerobic bacteria of the genus Actinomyces spp. In general, actinomycosis presents a latent clinical course that makes its diagnosis difficult. We describe a patient with empyema by Actinomyces spp. secondary to rupture into the pleural cavity of a liver abscess.

Clinical management and hospital outcomes of acute coronary syndrome patients in Mexico: The Third National Registry of Acute Coronary Syndromes (RENASICA III) / Abordaje clínico y evolución hospitalaria en pacientes mexicanos con sindrome coronario agudo: El Tercer Registro Nacional de Síndromes Coronarios Agudos (RENASICA III)

Abstract Objective To describe current management and clinical outcomes in patients hospitalized with an acute coronary syndrome (ACS) in Mexico. Methods RENASICA III was a prospective multicenter registry of consecutive patients hospitalized with an ACS. Patients had objective evidence of ischemic heart disease; those with type II infarction or secondary ischemic were excluded. Study design conformed to current quality recommendations. Results A total of 123 investigators at 29 tertiary and 44 community hospitals enrolled 8296 patients with an ACS (4038 with non-ST-elevation myocardial infarction/unstable angina [NSTEMI/UA], 4258 with ST-elevation myocardial infarction [STEMI]). The majority were younger (62 ± 12 years) and 76.0% were male. On admission 80.5% had ischemic chest pain lasting >20 min and clinical stability. Left ventricular dysfunction was more frequent in NSTEMI/UA than in those with STEMI (30.0% vs. 10.7%, p < 0.0001). In STEMI 37.6% received thrombolysis and 15.0% primary PCI. PCI was performed in 39.6% of NSTEMI/UA (early strategy in 10.8%, urgent strategy in 3.0%). Overall hospital death rate was 6.4% (8.7% in STEMI vs. 3.9% in NSTEMI/UA, p < 0.001). The strongest independent predictors of hospital mortality were cardiogenic shock (odds ratio 22.4, 95% confidence interval 18.3-27.3) and ventricular fibrillation (odds ratio 12.5, 95% confidence interval 9.3-16.7). Conclusion The results from RENASICA III establish the urgent need to develop large-scale regional programs to improve adherence to guideline recommendations in ACS, including rates of pharmacological thrombolysis and increasing the ratio of PCI to thrombolysis.

Resumen Objetivo Describir abordaje terapéutico actual y evolución en pacientes hospitalizados con un síndrome coronario agudo (SCA) en México. Métodos RENASICA III registro multicéntrico prospectivo de pacientes consecutivos con un SCA. Todos tuvieron demostración objetiva de enfermedad coronaria; se excluyeron infarto tipo II o isquemia secundaria. El diseño incluyó recomendaciones actuales de calidad. Resultados 123 investigadores en 29 hospitales de tercer nivel y en 44 de segundo ingresaron 8296 pacientes, 4038 con infarto del miocardio sin elevación del ST/angina inestable (IMSEST/AI) y 4258 con infarto del miocardio y elevación del ST (IMEST). La mayoría fueron jóvenes (62 ± 12 años) y el 76% del sexo masculino. Al ingreso 80.5% tuvo dolor torácico con perfil isquémico >20 minutos y estabilidad clínica. Se observó mayor disfunción ventricular en grupo con IMSEST/AI que en aquellos con IMEST (30.0% vs 10.7%, p <0.0001). En IMEST el 37.6% recibió trombolisis y el 15% angioplastía primaria. Este procedimiento se realizó en el 39.6% de los pacientes con IMSEST/AI (estrategia temprana 10.8%, estrategia urgente 3.0%). La mortalidad hospitalaria fue del 6.4% (8.7% IMEST vs. 3.9% IMSEST/AI, p <0.001). Los predictores independientes con mayor poder para mortalidad fueron choque cardiogénico (RM 22.4, 95% IC 18.3-27.3) y fibrilación ventricular (RM 12.5, 95% IC 9.3-16.7). Conclusión los resultados del RENASICA III establecen la urgente necesidad de desarrollar en SCA programas regionales a gran escala para mejorar el apego a la guías y recomendaciones, incluyendo mayor porcentaje de trombolisis e incrementar la proporción de angioplastia primaria.

Hemangioma cavernoso mediastinal / Mediastinal Cavernous Hemangioma

El hemangioma mediastinal es un tumor vascular benigno poco frecuente que representa el 0,5 % de los tumores mediastinales. Se describe el caso de un paciente de 65 años con un tumor de mediastino anterior correspondiente a un hemangioma cavernoso.

The mediastinal hemangioma is a rare benign vascular tumor representing 0.5 % of mediastinal tumors. We describe a case of a 65 year old patient with an anterior tumor of mediastinum corresponding to a cavernous hemangioma.

Engrosamiento nodular difuso de la pleura / Diffuse nodular thickening of the pleura

Paciente masculino de 52 años con dolor torácico de características pleuríticas y disnea de cuatro meses de evolución. La radiografía (imagen IA) y la tomografía computarizada (TC) de tórax (Figura IB), mostraron engrosamiento nodular difuso de la pleura y efusión pleural. El engrosamiento pleural se define por un espesor de la pleura > de 3 mm que puede ser focal o difuso. En la radiografía frontal se considera un engrosamiento pleural difuso a la alteración mayor de 25% de la superficie pleural (bilateral) o mayor de 50% (unilateral). En TC se puede considerar difuso al engrosamiento pleural con una longitud > 8 cm y un diámetro mayor de 5 cm . El engrosamiento del paciente: difuso, concéntrico y nodular sugiere enfermedad neoplásica (primaria o secundaria), principalmente: enfermedad metastásica, mesotelioma, linfoma y timoma invasivo. Ocasionalmente entidades infecciosas pueden presentar este hallazgo. La patología pleural del paciente confirmó mesotelioma maligno epitelioide. Este mesotelioma es más frecuente en personas entre la sexta y séptima década de la vida, predomina en hombres y se asocian a la exposición a asbestos.

Combinación de fibrosis pulmonar y enfisema / Combination Pulmonary Fibrosis and Emphysema

Objetivo: Describir las manifestaciones en tomografía computarizada de alta resolución (TCAR) de 21 pacientes con diagnóstico de combinación de fibrosis pulmonar y enfisema (CFPE) estudiados en el Hospital Universitario Mayor (HUM). Métodos: Serie de casos, descriptivo. Los 21 pacientes seleccionados cumplían los criterios de CFPE: Enfermedad parenquimatosa difusa con cambios significativos de fibrosis y enfisema mayor del 10 %. Los estudios radiológicos fueron analizados en consenso por dos radiólogos expertos en imágenes del tórax. Los datos clínicos se obtuvieron de la historia clínica y a través de llamadas telefónicas. Resultados: El promedio de edad de los pacientes fue de 67 años. El 68,4 % tenía antecedente de tabaquismo. Las alteraciones más frecuentes en TCAR fueron: opacidades intralobulillares (95,2 %), panal de abejas (95,2 %) y bronquiectasias de tracción (95,2 %). Los patrones de fibrosis y enfisema más frecuentes fueron neumonía intersticial usual (NIU) (54,5 %) y enfisema paraseptal (40,9 %). Predominaron las asociaciones de patrones de fibrosis y enfisema: combinación de patrón de NIU y enfisema paraseptal (33,3 %) y cambios no específicos de fibrosis con enfisema paraseptal (28,6 %). Hubo alta prevalencia de hipertensión pulmonar (81,8 %), sin embargo, el tamaño de muestra analizado fue bajo. Conclusiones: El patrón de NIU y los cambios de enfisema paraseptal fueron la asociación más frecuente, con alta prevalencia de hipertensión pulmonar. Las manifestaciones en TCAR fueron similares a las descritas en trabajos previos. La radiografía presentó un bajo rendimiento para detectar enfisema e hipertensión pulmonar. La mortalidad fue elevada.

Purpose: To describe the findings in high-resolution computed tomography (HRCT) of 21 patients diagnosed with combined pulmonary fibrosis and emphysema (CPFE) studied at the Hospital Universitario Mayor (HUM). Methods: Case series, descriptive. 21 patients studied in the HUM who met the diagnostic criteria of CFPE were selected: Diffuse parenchymal disease with significant changes of fibrosis and presence of emphysema with extension greater than 10%. Radiologic studies were reviewed in consensus by two radiologists experienced in chest images. Clinical data were obtained retrospectively from clinical records and through telephone calls. Results: The mean age of patients was 67 years. 68.4% had a history of smoking. The most frequent alterations in HRCT were: intralobular opacities (95.2%), honeycomb (95.2%) and traction bronchiectasis (95.2%). Patterns of fibrosis and emphysema which were most commonly found were usual interstitial pneumonia (UIP) (54.5%) and paraseptal emphysema (40.9%). The most frequent association patterns were combined NIU pattern and paraseptal emphysema (33.3%) and non-specific changes of fibrosis with paraseptal emphysema (28.6%). The prevalence of pulmonary hypertension in the cases studied was high (81.8%), however the analyzed sample size was low. Conclusions: Combined usual interstitial pneumonia and emphysema paraseptal changes was the most frequent pattern, with a high prevalence of pulmonary hypertension. The HRCT findings were similar to those described in previous studies. The x-ray showed a low capacity for detecting emphysema and pulmonary hypertension. Mortality was high.