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BACKGROUND Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. METHODS The INTERSTROKE study is a case­control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). FINDINGS Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46­1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61­2.11) than ICH (OR 1.19 95% CI 1.00­1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24­4.10) and PAR (18.6%, 15.1­22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63­2.87) and undetermined cause (OR 1.97, 95% CI 1.55­2.50). Both filtered (OR 1.73, 95% CI 1.50­1.99) and non-filtered (OR 2.59, 95% CI 1.79­3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69­2.27), ischemic stroke (OR 1.89, 95% CI 1.59­2.24) and ICH (OR 2.00, 95% CI 1.60­2.50). INTERPRETATION There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. FUNDING The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

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La neurorretinopatía macular aguda es una condición rara con patogenia microvascular. Se presenta con un inicio agudo con escotomas paracentrales correspondientes a lesiones paramaculares evidentes. Los avances en las imágenes multimodales permitieron caracterizar este trastorno de retina y crear nuevos conceptos. Serraf, en el 2013, identificó dos formas por medio de la tomografía de coherencia óptica dominio espectral: el tipo 1 conocido como maculopatía paracentral aguda media en la cual se observa una banda hiperreflectiva en la capa nuclear interna, y el tipo 2 en el cual la banda hiperreflectiva se ubica en la capa nuclear externa, que involucra la zona elipsoide y la zona de interdigitación con el epitelio pigmentario de la retina. Hasta el momento no existe cura; pero se puede actuar sobre los factores de riesgo. Por ser una condición rara y por no existir reportes hasta el momento en Cuba es que se presentan a continuación dos pacientes con cuadros clínicos similares de estas dos variantes; concluyendo la importancia que presentan las imágenes multimodales como medio auxiliar diagnóstico(AU)

Acute macular neuroretinopathy is a rare condition with complex pathogenesis and microvascular cause. It appears with acute onset, with paracentral scotomas corresponding to obvious paramacular lesions. Advances in multimodal imaging made it possible to characterize this retinal disorder and to create new concepts. Serraf, in 2013, identified two forms by spectral domain optical coherence tomography: type 1, known as paracentral acute middle maculopathy, in which a hyperreflective band is observed in the inner nuclear layer; and type 2, in which the hyperreflective band is located in the outer nuclear layer, involving the ellipsoid zone and the zone of interdigitation with the retinal pigment epithelium. Up to this moment, there is no cure; but it is possible to act on the risk factors. Because it is a rare condition and because there are no reports so far in Cuba, two patients with similar clinical pictures of these two variants are presented; concluding the importance of multimodal images as an auxiliary diagnostic tool(AU)

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La toxocariasis es una zoonosis prevalente con un importante impacto socioeconómico, particularmente en las comunidades pobres de todo el mundo. Es causada por formas larvarias de especies de nematodos, parásitos del género Toxocara. El espectro de manifestaciones clínicas en la toxocariasis varía ampliamente, desde casos asintomáticos a infecciones generalizadas. En el caso de la toxocariasis ocular, el deterioro de la agudeza visual es la manifestación más común cuando los síntomas están presentes. Las presentaciones oculares incluyen endoftalmitis crónica, granuloma de polo posterior o granuloma periférico. Presentamos el caso de una paciente de 12 años, con toxocariasis ocular en forma de granuloma de polo posterior con bandas traccionales a vítreo, acompañada de una lesión hiperpigmentada en el área macular en fase cicatrizal. El propósito de esta publicación es describir las múltiples complicaciones oculares que pueden concomitar en el paciente con toxocariasis ocular, que finalmente conllevan a una pérdida visual irreversible(AU)

Toxocariasis is a prevalent zoonosis with a significant socioeconomic impact, particularly in poor communities around the world. It is caused by larval forms of nematode species, parasites of the Toxocara genus. The spectrum of clinical manifestations in toxocariasis varies widely from asymptomatic cases to systemic infections. In the case of ocular toxocariasis, impaired visual acuity is the most common manifestation when symptoms are present. Ocular presentations include chronic endophthalmitis, posterior pole granuloma, or a peripheral granuloma. We present the case of a 12-year-old patient with ocular toxocariasis in the form of a posterior pole granuloma with vitreous tractional bands, which is accompanied by a hyperpigmented lesion in the macular area in the healing phase. The purpose of our publication is to highlight the multiple ocular complications that can occur in patients with ocular toxocariasis, which ultimately lead to irreversible visual loss(AU)

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El desprendimiento de la capa bacilar de la retina es la separación de los segmentos internos de los fotorreceptores del resto de la retina neurosensorial, o separación entre la zona miode y elipsoide de la retina, que en un hallazgo reciente se puede identificar mediante la tomografía de coherencia óptica de dominio espectral. El objetivo es actualizar los conocimientos sobre el desprendimiento de la capa bacilar de la retina y el uso de la tomografía de coherencia óptica de dominio espectral en las enfermedades oculares que están asociadas con este signo. Se consultaron las fuentes bibliográficas como Google académico, SciELO LAC, Medline y MEDICARIBE. Se limitaron los resultados al idioma español e inglés y a los últimos cinco años. Se recuperaron 54 documentos, de ellos 18 resultaron relevantes a esta investigación. Los autores más mencionados fueron Ramtohul, Metha y Cicinelli. Ellos trabajaron el signo clínico en cuestión y reportaron la experiencia en la atención a los pacientes aquejados con esta enfermedad ocular. El desprendimiento de la capa bacilar de la retina es un signo presente en varias enfermedades asociadas a inflamación del segmento posterior ocular. La tomografía de coherencia óptica de dominio espectral es una técnica efectiva para determinarlo, aunque estos planteamientos aún son escasos en la literatura, lo cual reafirma la importancia científica de continuar los estudios a partir de hipótesis iniciales desde el punto de vista histológico y tomográfico(AU)

Retinal bacillary layer detachment is the separation of the inner segments of the photoreceptors from the rest of the neurosensory retina, or separation between the myode and ellipsoid zone of the retina, which in a recent finding can be identified by spectral-domain optical coherence tomography. The objective is to update the knowledge about the detachment of the bacillary layer of the retina and the use of spectral-domain optical coherence tomography in ocular diseases that are associated with this sign. Bibliographic sources such as academic Google, SciELO LAC, MEDLINE and MEDICARIBE were consulted. Fifty-four documents were retrieved, of which 18 were relevant to this research. The results were limited to the Spanish and English language and to the last five years. The most mentioned authors were Ramtohul, Metha and Cicinelli. They worked on the clinical sign in question and reported the experience in caring for patients afflicted with this ocular disease. Detachment of the bacillary layer of the retina is a sign present in several diseases associated with ocular posterior segment inflammation. Spectral-domain optical coherence tomography is an effective technique to determine it, although it is still scarce in the literature, which reaffirms the scientific validity of continuing studies from initial hypotheses from the histological and tomographic point of view(AU)

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Unlike medications that contain fixed-dose combinations, such as those recommended by clinical guidelines for treating high blood pressure, the so-called polypills contain several drugs that simultaneously treat two or more cardiovascular conditions or risk factors. They were proposed 2 decades ago, both for primary and secondary prevention with the hypothesis that they could have wide dissemination and population penetration, improving the use of therapeutics with proven benefits individually, thanks to an increase in patient adherence by reducing the number of daily tablets and also by having an equal or lower cost. In this simple review, we present a look at risk stratification different from that posed by clinical scores and summarize the benefits of polypills in the treatment of risk factors and in the reduction of major cardiovascular events. Additionally, we review the clinical messages of the HOPE-3 trial, which aim to control two of the most prevalent conditions, such as high blood pressure and high cholesterol, through a combination of candesartan, hydrochlorothiazide and rosuvastatin. Finally, we propose its potential indication in a heterogeneous health system such as that of our country, both at the population level based on intermediate or low risk, determined intuitively or using a risk calculator, as well as in the personalized care that is practiced in many health scenarios.

A diferencia de los medicamentos que contienen combinaciones de dosis fijas, como los recomendados por las guías clínicas para tratar la hipertensión arterial, las llamadas polipíldoras contienen varios fármacos que tratan simultáneamente dos o más afecciones cardiovasculares o factores de riesgo. Se propusieron hace 2 décadas, tanto para prevención primaria como secundaria, con la hipótesis de que tengan amplia difusión y penetración poblacional, es decir, que mejoren el uso de terapéuticas con probados beneficios en forma individual, gracias a un incremento en la adherencia de los pacientes al reducir el número de comprimidos diarios y también al tener un costo igual o menor. En esta revisión simple, planteamos una mirada de la estratificación del riesgo distinta a la planteada por los puntajes clínicos y resumimos los beneficios de las polipíldoras en el tratamiento de los factores de riesgo y en la reducción de eventos cardiovasculares mayores. Adicionalmente, repasamos los mensajes clínicos del ensayo HOPE-3, que apuntan a controlar dos de las condiciones más prevalentes, como son la hipertensión arterial y el colesterol elevado, mediante una combinación de candesartán, hidroclorotiazida y rosuvastatina. Finalmente, proponemos su potencial indicación en un sistema sanitario heterogéneo como el de nuestro país, tanto a nivel poblacional basado en el riesgo intermedio o bajo, determinado intuitivamente o usando un calculador de riesgo, así como también en la atención personalizada que se practica en muchos escenarios sanitarios.

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Resumen A diferencia de los medicamentos que contienen combinaciones de dosis fijas, como los recomendados por las guías clínicas para tratar la hipertensión arterial, las llamadas polipíldoras contienen varios fármacos que tratan simultáneamente dos o más afecciones cardiovasculares o factores de riesgo. Se propusieron hace 2 décadas, tanto para prevención primaria como secundaria, con la hipótesis de que tengan amplia difusión y penetración poblacional, es decir, que mejoren el uso de terapéuticas con probados beneficios en forma individual, gracias a un incremento en la adherencia de los pacientes al reducir el número de com primidos diarios y también al tener un costo igual o menor. En esta revisión simple, planteamos una mirada de la estratificación del riesgo distinta a la planteada por los puntajes clínicos y resumimos los beneficios de las polipíldoras en el tratamiento de los factores de riesgo y en la reducción de eventos cardiovasculares mayores. Adicionalmente, repasamos los mensajes clínicos del ensayo HOPE-3, que apuntan a controlar dos de las con diciones más prevalentes, como son la hipertensión arterial y el colesterol elevado, mediante una combinación de candesartán, hidroclorotiazida y rosuvastatina. Finalmente, proponemos su potencial indicación en un sistema sanitario heterogéneo como el de nuestro país, tanto a nivel poblacional basado en el riesgo intermedio o bajo, determinado intuitivamente o usando un calculador de riesgo, así como también en la atención personalizada que se practica en muchos escenarios sanitarios.

Abstract Unlike medications that contain fixed-dose combinations, such as those recommended by clinical guidelines for treating high blood pressure, the so-called polypills contain several drugs that simultaneously treat two or more cardiovascular conditions or risk factors. They were proposed 2 decades ago, both for primary and secondary prevention with the hypothesis that they could have wide dissemination and population penetration, improving the use of therapeutics with proven benefits individually, thanks to an increase in patient adherence by reducing the number of daily tablets and also by having an equal or lower cost. In this simple review, we present a look at risk stratification different from that posed by clinical scores and summarize the benefits of polypills in the treatment of risk factors and in the reduction of major cardiovascular events. Additionally, we review the clinical messages of the HOPE-3 trial, which aim to control two of the most prevalent conditions, such as high blood pressure and high cholesterol, through a combination of candesartan, hydrochlorothiazide and rosuvastatin. Finally, we propose its potential indication in a heterogeneous health system such as that of our country, both at the population level based on intermediate or low risk, determined intuitively or using a risk calculator, as well as in the personalized care that is practiced in many health scenarios.

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Las membranas neovasculares coroidea representan el crecimiento de nuevos vasos sanguíneos originados de la coriocapilar hacia el epitelio pigmentario de la retina o el espacio subretinal por una disrupción de la membrana de Bruch ocasionado por la inflamación prolongada. El desarrollo de las membranas neovasculares coroidea está estrechamente conectado a la morbilidad asociada con la coroidopatía punteada interna y puede ser su primera forma de presentación. La coroidopatía punteada interna es clasificada como una de las enfermedades de los síndromes de puntos blancos evanescentes, es una enfermedad infrecuente, bilateral y de origen desconocido. Se presenta un caso clínico de un paciente al cual se le diagnostica membranas neovasculares coroidea en el curso de una coroidopatía punteada interna con una presentación atípica o previa a las lesiones de coroiditis. La coroidopatía punteada interna complicada con membranas neovasculares coroidea compromete la visión central de forma considerable en pacientes jóvenes(AU)

Choroidal neovascular membranes represent the growth of new blood vessels originating from the choriocapillaris into the retinal pigment epithelium or subretinal space due to disruption of Bruch's membrane caused by prolonged inflammation. The development of choroidal neovascular membranes is closely connected to the morbidity associated with punctate inner choroidopathy and may be its first form of manifestation. Punctate Inner choroidopathy is classified as one of the evanescent white dot syndromes diseases, is a rare, bilateral disease of unknown origin. We present a case report of a patient diagnosed with choroidal neovascular membranes while suffering from punctate inner choroidopathy with an atypical manifestation or prior to choroiditis lesions. Punctate Inner choroidopathy when complicated with choroidal neovascular membranes compromises significantly the central vision in young patients(AU)

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Resumen Objetivo: Analizar la utilidad del modelo predictivo de bacteriemia (5MPB-Toledo) en los mayores de 65 años atendidos por infección en el servicio de urgencias (SU). Material y Método: Estudio observacional prospectivo y multicéntrico de los hemocultivos (HC) obtenidos en pacientes mayores de 65 años atendidos por infección en 66 SU españoles desde el 1 de diciembre de 2019 hasta el 30 de abril de 2020. Se analizó la capacidad predictiva del modelo con el área bajo la curva (ABC) de la característica operativa del receptor (COR) y se calculó el rendimiento diagnóstico de los puntos de corte (PC) del modelo elegido con los cálculos de la sensibilidad, la especificidad, el valor predictivo positivo y el valor predictivo negativo. Resultados: Se incluyeron 2.401 episodios de HC extraídos. De ellos, se consideró como bacteriemia verdadera a 579 (24,11%) y como HC negativo a 1.822 (75,89%). Entre los negativos, 138 (5,74%) se consideraron contaminados. Se categorizó a los pacientes en bajo (0-2 puntos), moderado (3-5 puntos) y alto (6-8 puntos) riesgo, con una probabilidad de bacteriemia de 1,2%, 18,1% y 80,7%, respectivamente. El ABC-COR del modelo tras remuestreo fue de 0,908 (IC 95%: 0,897-0,924). El rendimiento diagnóstico del modelo, considerando un PC ≥ 5 puntos, obtiene una sensibilidad de 94% (IC 95%:92-96), especificidad de 77% (IC 95%:76-79) y un valor predictivo negativo de 97% (IC 95%:96-98). Conclusión: El modelo 5MPB-Toledo es de utilidad para predecir bacteriemia en los mayores de 65 años atendidos en el SU por un episodio de infección.

Abstract Objective: To analyse a risk score to predict bacteremia (MPB5-Toledo) in the patients aged older 65 years seen in the emergency departments (ED) due to infections. Patients and Methods: Prospective and multicenter observational cohort study of the blood cultures (BC) ordered in 66 Spanish ED for patients aged older 65 years seen from December 1, 2019, to April 30, 2020. The predictive ability of the model was analyzed with the area under the Receiver Operating Characteristic curve (AUC-ROC). The prognostic performance for true bacteremia was calculated with the cut-off values chosen for getting the sensitivity, specificity, positive predictive value and negative predictive value. Results: A total of 2.401 blood samples wered cultured. True cases of bacteremia were confirmed in 579 (24.11%). The remaining 1.822 cultures (75.89%) wered negative. And, 138 (5.74%) were judged to be contaminated. Low risk for bacteremia was indicated by a score of 0 to 2 points, intermediate risk by 3 to 5 points, and high risk by 6 to 8 points. Bacteremia in these 3 risk groups was predicted for 1.2%, 18.1%, and 80.7%, respectively. The model´s area under the receiver ope rating characteristic curve was 0.908 (95% CI, 0.897-0.924). The prognostic performance with a model´s cut-off value of ≥ 5 points achieved 94% (95% CI: 92-96) sensitivity, 77% (95% CI: 76-79) specificity, and negative predictive value of 97% (95% CI: 96-98). Conclusion: The 5MPB-Toledo score is useful for predicting bacteremia in the patients aged older 65 years seen in the emergency departments due to infections.

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Objetivo: Identificar la relación de los pseudodrusen reticulares con la degeneración macular asociada a la edad mediante imágenes tomográficas. Método: Estudio observacional, descriptivo y transversal en pacientes con pseudodrusen reticulares atendidos en consulta de retina a los que se les realizó tomografía de coherencia óptica espectral desde enero de 2009 hasta diciembre de 2014 en el Instituto Cubano de Oftalmología "Ramón Pando Ferrer". La población estuvo constituida por 69 pacientes de 55 años y más con pseudodrusen reticulares en dichas imágenes. Resultados: Los pseudodrusen predominaron en pacientes con edades comprendidas entre los 70 y 79 años para un 49,3 por ciento. El sexo femenino fue el más numeroso con un 76,8 por ciento. De los 122 ojos con pseudodrusen, 86 presentaron algún signo de degeneración macular asociada a la edad representado por el 70,5 por ciento. El 58,1 por ciento de estos últimos tuvo la forma avanzada. La membrana neovascular tipo II fue la más frecuente con un 58,0 por ciento. El grosor coroideo se estimó disminuido en el 77,9 por ciento de los casos. Conclusiones: Los pseudodrusen reticulares mantienen una relación directa con la degeneración macular asociada a la edad e influyen en la progresión de esta(AU)

Objective: To identify the relationship of reticular pseudodrusen with age-related macular degeneration using tomographic imaging. Methods: An observational, descriptive and cross-sectional study was conducted in patients with reticular pseudodrusen seen in retina consultation who underwent spectral optical coherence tomography from January 2009 to December 2014 at the Cuban Institute of Ophthalmology "Ramón Pando Ferrer". The population consisted of 69 patients aged 55 years and older with reticular pseudodrusen in these images. Results: Pseudodrusen predominated in patients between 70 and 79 years of age (49.3 percent). The female gender was the most numerous with 76.8 percent. Out of the 122 eyes with pseudodrusen, 86 showed some sign of age-related macular degeneration (70.5 percent). Out of the latter, 58.1 percent had the advanced form. Type II neovascular membrane was the most frequent with 58.0 percent. Choroidal thickness was estimated decreased in 77.9 percent of cases. Conclusions: Reticular pseudodrusen maintain a direct relationship with age-related macular degeneration and influence its progression(AU)

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AIMS: In a multinational South American cohort, we examined variations in CVD incidence and mortality rates between subpopulations stratified by country, by sex and by urban or rural location. We also examined the contributions of 12 modifiable risk factors to CVD development and to death. METHODS AND RESULTS: This prospective cohort study included 24 718 participants from 51 urban and 49 rural communities in Argentina, Brazil, Chile, and Colombia. The mean follow-up was 10.3 years. The incidence of CVD and mortality rates were calculated for the overall cohort and in subpopulations. Hazard ratios and population attributable fractions (PAFs) for CVD and for death were examined for 12 common modifiable risk factors, grouped as metabolic (hypertension, diabetes, abdominal obesity, and high non-HDL cholesterol), behavioural (tobacco, alcohol, diet quality, and physical activity), and others (education, household air pollution, strength, and depression). Leading causes of death were CVD (31.1%), cancer (30.6%), and respiratory diseases (8.6%). The incidence of CVD (per 1000 person-years) only modestly varied between countries, with the highest incidence in Brazil (3.86) and the lowest in Argentina (3.07). There was a greater variation in mortality rates (per 1000 person-years) between countries, with the highest in Argentina (5.98) and the lowest in Chile (4.07). Men had a higher incidence of CVD (4.48 vs. 2.60 per 1000 person-years) and a higher mortality rate (6.33 vs. 3.96 per 1000 person-years) compared with women. Deaths were higher in rural compared to urban areas. Approximately 72% of the PAF for CVD and 69% of the PAF for deaths were attributable to 12 modifiable risk factors. For CVD, largest PAFs were due to hypertension (18.7%), abdominal obesity (15.4%), tobacco use (13.5%), low strength (5.6%), and diabetes (5.3%). For death, the largest PAFs were from tobacco use (14.4%), hypertension (12.0%), low education (10.5%), abdominal obesity (9.7%), and diabetes (5.5%). CONCLUSIONS: Cardiovascular disease, cancer, and respiratory diseases account for over two-thirds of deaths in South America. Men have consistently higher CVD and mortality rates than women. A large proportion of CVD and premature deaths could be averted by controlling metabolic risk factors and tobacco use, which are common leading risk factors for both outcomes in the region.

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Importance: Hospitalized patients with COVID-19 pneumonia have high rates of morbidity and mortality. Objective: To assess the efficacy of colchicine in hospitalized patients with COVID-19 pneumonia. Design, Setting, and Participants: The Estudios Clínicos Latino América (ECLA) Population Health Research Institute (PHRI) COLCOVID trial was a multicenter, open-label, randomized clinical trial performed from April 17, 2020, to March 28, 2021, in adults with confirmed or suspected SARS-CoV-2 infection followed for up to 28 days. Participants received colchicine vs usual care if they were hospitalized with COVID-19 symptoms and had severe acute respiratory syndrome or oxygen desaturation. The main exclusion criteria were clear indications or contraindications for colchicine, chronic kidney disease, and negative results on a reverse transcription-polymerase chain reaction test for SARS-CoV-2 before randomization. Data were analyzed from June 20 to July 25, 2021. Interventions: Patients were assigned in a 1:1 ratio to usual care or usual care plus colchicine. Colchicine was administered orally in a loading dose of 1.5 mg immediately after randomization, followed by 0.5 mg orally within 2 hours of the initial dose and 0.5 mg orally twice a day for 14 days or discharge, whichever occurred first. Main Outcomes and Measures: The first coprimary outcome was the composite of a new requirement for mechanical ventilation or death evaluated at 28 days. The second coprimary outcome was death at 28 days. Results: A total of 1279 hospitalized patients (mean [SD] age, 61.8 [14.6] years; 449 [35.1%] women and 830 [64.9%] men) were randomized, including 639 patients in the usual care group and 640 patients in the colchicine group. Corticosteroids were used in 1171 patients (91.5%). The coprimary outcome of mechanical ventilation or 28-day death occurred in 160 patients (25.0%) in the colchicine group and 184 patients (28.8%) in the usual care group (hazard ratio [HR], 0.83; 95% CI, 0.67-1.02; P = .08). The second coprimary outcome, 28-day death, occurred in 131 patients (20.5%) in the colchicine group and 142 patients (22.2%) in the usual care group (HR, 0.88; 95% CI, 0.70-1.12). Diarrhea was the most frequent adverse effect of colchicine, reported in 68 patients (11.3%). Conclusions and Relevance: This randomized clinical trial found that compared with usual care, colchicine did not significantly reduce mechanical ventilation or 28-day mortality in patients hospitalized with COVID-19 pneumonia. Trial Registration: ClinicalTrials.gov Identifier: NCT04328480.

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Renal cell carcinoma accounts for 2-3% of all malignant neoplasms. Metastatic disease of the spine is common and 50% of bone metastases are already present at the time of primary diagnosis. Bone metastases from renal cell carcinoma are difficult to manage, especially vertebral localization.A 48-year-old woman was diagnosed with renal cell carcinoma in the context of low back pain. The patient presented two skeleton metastases at diagnosis (T11 and 5th rib). The patient received neoadjuvant treatment with cabozantinib, followed by removal of the renal tumor. Radiotherapy was administered for the lumbar lesion. In spite of the radiotherapy treatment, increased low back pain limiting mobility and ambulation. MRI showed an occupation of the spinal canal, without neurological lesion. The SINS scale revealed a score of 14 (vertebral instability). The patient's prognosis was greater than 12 months according to the Tokuhashi score. Based on clinical and mechanical criteria, surgical treatment of the vertebral lesion was decided. T11 vertebrectomy was performed, the reconstruction was made with an expandable cage, and T8 a L2 posterior spinal arthrodesis. A partial resection of the fifth rib was performed in order to remove the whole macroscopic tumor. After 3 months, she was diagnosed with a local infection, treated by irrigation, debridement and antibiotherapy, with good evolution. At 1-year follow-up, she has no low back pain or functional limitation. Follow-up chest-abdomen-pelvis computed CT scan showed absence of disease progression, furthermore, the vertebral arthrodesis shows fusion signs. At the time of this report, there are no clinical or radiological data of infection

El carcinoma de células renales representa el 2-3% de todas las neoplasias malignas. La enfermedad metastásica de la columna vertebral es frecuente y el 50% de las metástasis óseas ya están presentes en el momento del diagnóstico. Las metástasis óseas del carcinoma de células renales son difíciles de manejar, especialmente en localización vertebral.Una mujer de 48 años fue diagnosticada de carcinoma de células renales en el contexto de un dolor lumbar. La paciente presentaba dos metástasis óseas en el momento del diagnóstico (T11 y 5ª costilla). Inicialmente recibió tratamiento neoadyuvante con cabozantinib, seguido de la extirpación quirúrgica del tumor renal. Se administró radioterapia para la lesión lumbar. A pesar del tratamiento radioterápico, aumentó el dolor lumbar con limitación para la movilidad y la deambulación. La RM mostró una ocupación del canal espinal, sin lesión neurológica. La escala SINS reveló una puntuación de 14 (inestabilidad vertebral). El pronóstico de la paciente era superior a 12 meses según la puntuación de Tokuhashi. Basándose en criterios clínicos y mecánicos, se decidió el tratamiento quirúrgico de la lesión vertebral. Se realizó una vertebrectomía de T11, para la reconstrucción se usó una caja extensible, junto con una artrodesis vertebral T8-L2. Se realizó una resección parcial de la quinta costilla para eliminar todo el tumor macroscópico. A los 3 meses de la cirugía la paciente fue diagnosticada de infección local, tratada mediante irrigación, desbridamiento y antibioterapia, con buena evolución. Al año de seguimiento, no presenta dolor lumbar ni limitación funcional. La tomografía computarizada de tórax-abdomen-pelvis de seguimiento mostró ausencia de progresión de la enfermedad, además, la artrodesis vertebral muestra signos de fusión. En el momento de este informe, no hay datos clínicos ni radiológicos de infección.

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Objetivo: Determinar las características clínicas y epidemiológicas de la neovascularización coroidea en los pacientes con uveítis. Métodos: Se realizó un estudio observacional, descriptivo y transversal en pacientes con diagnóstico de neovascularización coroidea asociada a uveítis, atendidos en el Servicio de Uveítis e Inflamaciones Oculares del Instituto Cubano de Oftalmología "Ramón Pando Ferrer". Resultados: Esta entidad predominó en el sexo femenino, en edad pediátrica y en jóvenes. Se asoció con mayor frecuencia a enfermedades infecciosas, como la toxoplasmosis ocular, y un pequeño número de pacientes desarrolló membrana neovascular coroidea bilateral. Las membranas localizadas con mayor frecuencia fueron las subfoveales. Por angiografía fluoresceínica predominaron las clásicas, mientras el grosor de la membrana neovascular coroidea fue mayor que el grosor foveal central. La agudeza visual mejor corregida en la mayoría de nuestros pacientes fue menor de 85 VAR. Conclusión: La membrana neovascular coroidea asociada a las uveítis es reconocida como una complicación infrecuente, pero compromete de forma severa la visión en estos pacientes(AU)

Objective. To determine the clinical-epidemiological characteristics of choroidal neovascularization in patients with uveitis. Method. An observational, descriptive, cross-sectional study was carried out in patients with a diagnosis of choroidal neovascularization associated with uveitis, attended in the Uveitis and Ocular Inflammations Service of the Cuban Institute of Ophthalmology "Ramón Pando Ferrer". Results. This entity predominated in the female sex, in pediatric age and youth. It was more frequently associated with infectious diseases, such as ocular toxoplasmosis, and a small number of patients developed bilateral choroidal neovascular membrane. The most frequent location of the membranes were the subfoveal ones, by fluorescein angiography the predominantly classic ones and the thickness of the choroidal neovascular membrane was greater than the central foveal thickness. The best corrected visual acuity in most of our patients was less than 85 VAR. Conclusion. CNVM associated with uveitis is recognized as an uncommon complication but one that severely compromises vision in these patients(AU)

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AIMS Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated. METHODS AND RESULTS After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64­0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68­1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69­0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69­0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years. CONCLUSION The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect.

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Objective Recent European Guidelines for Diabetes, Prediabetes and Cardiovascular Diseases introduced a shift in managing patients with type 2 diabetes at high risk for or established cardiovascular (CV) disease by recommending GLP-1 receptor agonists and SGLT-2 inhibitors as initial glucose-lowering therapy. This is questioned since outcome trials of these drug classes had metformin as background therapy. In this post hoc analysis, the effect of dulaglutide on CV events was investigated according to the baseline metformin therapy by means of a subgroup analysis of the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial. Research design and methods Patients in REWIND (n = 9901; women: 46.3%; mean age: 66.2 years) had type 2 diabetes and either a previous CV event (31%) or high CV risk (69%). They were randomized (1:1) to sc. dulaglutide (1.5 mg/weekly) or placebo in addition to standard of care. The primary outcome was the first of a composite of nonfatal myocardial infarction, nonfatal stroke, and death from cardiovascular or unknown causes. Key secondary outcomes included a microvascular composite endpoint, all-cause death, and heart failure. The effect of dulaglutide in patients with and without baseline metformin was evaluated by a Cox regression hazard model with baseline metformin, dulaglutide assignment, and their interaction as independent variables. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by a Cox regression model with adjustments for factors differing at baseline between people with vs. without metformin, identified using the backward selection. Results Compared to patients with metformin at baseline (n = 8037; 81%), those without metformin (n = 1864; 19%) were older and slightly less obese and had higher proportions of women, prior CV events, heart failure, and renal disease. The primary outcome occurred in 976 (12%) participants with baseline metformin and in 281 (15%) without. There was no significant difference in the effect of dulaglutide on the primary outcome in patients with vs. without metformin at baseline [HR 0.92 (CI 0.81­1.05) vs. 0.78 (CI 0.61­0.99); interaction P = 0.18]. Findings for key secondary outcomes were similar in patients with and without baseline metformin. Conclusion This analysis suggests that the cardioprotective effect of dulaglutide is unaffected by the baseline use of metformin therapy.

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OBJECTIVE: In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS: In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS: Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02-1.06, P < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85-1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment-baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03-1.12; P = 0.0002) for incident type 2 diabetes. CONCLUSIONS: In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.

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AIMS: Statins are pivotal to the secondary prevention of major adverse cardiovascular events, but some patients are statin-intolerant. We examined the effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab on the risk of major adverse cardiovascular events according to the intensity of background statin treatment. METHODS AND RESULTS: The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with acute coronary syndrome and dyslipidaemia despite intensive or maximum-tolerated statin treatment (including no statin if intolerance was documented). The primary outcome (major adverse cardiovascular events) comprised coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina. Median follow-up was 2.8 years. Baseline statin treatment was high-intensity (88.8%), low/moderate-intensity (8.7%) or none (2.4%). Median baseline low-density lipoprotein cholesterol was 86, 89 and 139 mg/dL (P < 0.001) in these statin treatment categories, respectively. Alirocumab produced similar relative reductions in low-density lipoprotein cholesterol from baseline across statin treatment subgroups, but the mean absolute reductions differed (52.9, 56.7 and 86.1 mg/dL, respectively; P < 0.001). With placebo, the incidence of major adverse cardiovascular events was highest in the no statin subgroup (10.8%, 10.7% and 26.0% respectively). Alirocumab reduced major adverse cardiovascular events in each statin subgroup (hazard ratio 0.88, 95% confidence interval (CI) 0.80-0.96; 0.68, 0.49-0.94; and 0.65, 0.44-0.97, respectively; Pinteraction = 0.14) with a gradient of absolute risk reduction: 1.25%, 95% CI 0.34-2.16; 3.16%, 0.38-5.94; 7.97%, 0.42-15.51; Pinteraction = 0.106). CONCLUSIONS: PCSK9 inhibition with alirocumab reduces the relative risk of major adverse cardiovascular events after acute coronary syndrome irrespective of background statin treatment. However, patients on no statin are at high absolute risk for recurrent major adverse cardiovascular events; alirocumab substantially reduces that risk. PCSK9 inhibition may be an important therapeutic strategy for statin-intolerant patients with acute coronary syndrome.

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OBJECTIVE: Previous prospective studies on the association of white rice intake with incident diabetes have shown contradictory results but were conducted in single countries and predominantly in Asia. We report on the association of white rice with risk of diabetes in the multinational Prospective Urban Rural Epidemiology (PURE) study. RESEARCH DESIGN AND METHODS: Data on 132,373 individuals aged 35-70 years from 21 countries were analyzed. White rice consumption (cooked) was categorized as <150, ≥150 to <300, ≥300 to <450, and ≥450 g/day, based on one cup of cooked rice = 150 g. The primary outcome was incident diabetes. Hazard ratios (HRs) were calculated using a multivariable Cox frailty model. RESULTS: During a mean follow-up period of 9.5 years, 6,129 individuals without baseline diabetes developed incident diabetes. In the overall cohort, higher intake of white rice (≥450 g/day compared with <150 g/day) was associated with increased risk of diabetes (HR 1.20; 95% CI 1.02-1.40; P for trend = 0.003). However, the highest risk was seen in South Asia (HR 1.61; 95% CI 1.13-2.30; P for trend = 0.02), followed by other regions of the world (which included South East Asia, Middle East, South America, North America, Europe, and Africa) (HR 1.41; 95% CI 1.08-1.86; P for trend = 0.01), while in China there was no significant association (HR 1.04; 95% CI 0.77-1.40; P for trend = 0.38). CONCLUSIONS: Higher consumption of white rice is associated with an increased risk of incident diabetes with the strongest association being observed in South Asia, while in other regions, a modest, nonsignificant association was seen.

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RESUMEN El agujero macular es un desorden de la interface vitreorretinal definido como un defecto de espesor completo desde la membrana limitante interna hasta los segmentos externos de los fotorreceptores, que normalmente involucra a la fóvea. Con el desarrollo de la tomografía de coherencia óptica se han mejorado el diagnóstico, el tratamiento y el seguimiento de las enfermedades de la interface vitreorretinal, entre ellas el agujero macular. La vitrectomía pars plana es la técnica quirúrgica de elección para el agujero macular. Se presenta una paciente de 75 años, pseudofáquica, con mejor agudeza visual corregida en el ojo derecho de 0,1 Snellen. Se diagnostica agujero macular grande (810 µm) según su mínima apertura, con 8 meses de evolución. Se realizó vitrectomía pars plana, el levantamiento de la hialodes posterior, el flap invertido de membrana limitante interna, el uso de hexafluoruro de azufre en mezcla 20 por ciento y el posicionamiento de la paciente 24-72 horas. Se logró el cierre anatómico del agujero macular y la recuperación visual de 0,6 Snellen a los seis meses del tratamiento quirúrgico(AU)

ABSTRACT Macular hole is a disorder of the vitreous-retina interface defined as a full-thickness defect from the internal limiting membrane to the external segments of photoreceptors which typically involves the fovea. The development of optical coherence tomography has improved the diagnosis, treatment and follow-up of vitreous-retina interface diseases, among them macular hole. Pars plana vitrectomy is the surgical technique of choice for macular hole. A case is presented of a female 75-year-old pseudophakic patient with best corrected right eye visual acuity of 0.1 on the Snellen chart. Large macular hole is diagnosed (810 µm) according to its minimum opening, of 8 month's evolution. The following procedures were performed: pars plana vitrectomy, posterior hyalode lifting, inverted internal limiting membrane flap, use of sulfur hexafluoride in a 20% mixture, and positioning of the patient for 24-72 hours. Anatomical closure of the macular hole and a visual recovery of 0.6 Snellen were achieved six months after surgery(AU)

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