Uso de remdesivir en ciclos repetidos y terapia de mantenimiento con emtricitabina/tenofovir contra SARS-CoV-2 persistente en paciente inmunocomprometido / Use of repeated courses of remdesivir and maintenance treatment with emtricitabine/tenofovir against persistent SARS-CoV-2 in immunocompromised patient

El estado inmunitario del organismo es determinante en la evolución de la infección producida por el virus SARS-CoV-2. La inmunosupresión constituye uno de los factores de riesgo que incrementa la reactivación del virus en el organismo, sumado al propio estado de salud del hospedador y factores virológicos como la carga viral y el genotipo del virus (Ye et al. 2020). El Grupo de Investigación Long COVID ACTS sugiere la importante actividad de los anticuerpos en el control de la enfermedad, pues una actividad inmunitaria debilitada y ausencia de respuesta humoral parece aumentar la persistencia del virus en el organismo, con la consecuente subsistencia de la sintomatología dando lugar a una situación de COVID persistente o long COVID, término que se define como “la persistencia o desarrollo de síntomas más allá de las 4 semanas desde el inicio de la enfermedad” (Naeije & Caravita, 2021). El COVID persistente surge con mayor frecuencia en pacientes de edad avanzada, con una o más comorbilidades y un estado inmunitario comprometido. Presentamos un caso de un varón de 72 años diagnosticado de leucemia linfocítica crónica en tratamiento quimioterápico, que dio positivo en la prueba de Reacción en Cadena de la Polimerasa (PCR) con un umbral de ciclos (CT) menor a 20 durante más de 90 días y una sintomatología severa. El caso fue valorado por un equipo multidisciplinar. Se planteó la utilidad de tratamientos como el uso de ciclos repetidos de remdesivir seguido de tratamiento mantenido con emtricitabina/tenofovir disoproxilo. (AU)

The body’s immune system status is decisive in the evolution of the infection caused by the SARS-CoV-2 virus. Immunosuppression along with host health status and virologic factors such as viral load and variant genotype are risk factors that increase the possibility of viral reactivation (Ye et al. 2020). The group Long COVID ACTS suggests the important activity of antibodies to control the disease. A weakened immune system and lack of humoral response appear to increase the persistence of the virus in the body and the consequent persistence of symptoms leading to a persistent or long COVID situation, which is defined as “the persistence or development of symptoms beyond 4 weeks from the onset of the disease” (Naeije & Caravita, 2021). Persistent COVID is more frequent in elderly patients, with comorbidities and immunocompromised status. We present a case of a 72-year-old man diagnosed with chronic lymphocytic leukemia under chemotherapy treatment. COVID-19 polymerase chain reaction (PCR) testing was positive with cycle threshold (CT) values <20 for more than 90 days and severe symptoms. The case was evaluated by a multidisciplinary team. Repeated courses of remdesivir and maintenance treatment with emtricitabine/tenofovir disoproxil fumarate were applied. (AU)

Latrogenic Cushing’s syndrome by an interaction between cobicistat and fluticasone: a case report / Síndrome de Cushing yatrogénico asociado a la interacción entre cobicistat y fluticasona: caso clínico

We report a case of iatrogenic Cushing’s syndrome associated with an interaction between cobicistat and fluticasone in a seropositive woman treated with elvitegravir/cobicistat/emtricitabina/TAF (Genvoya®). This case highlights the importance to review interactions between antirretroviral therapy and other drugs, especially when antirretroviral scheme includes protease inhibitors enhanced with ritonavir or cobicistat. These enhancers interfere the cytochrome P-450 metabolic pathway. A large number of drugs are metabolized by cytochrome P-450 and may be altered by cobicistat or ritonavir. (AU)

Presentamos un caso de síndrome de Cushing asociado a la interacción entre cobicistat y fluticasona en una mujer seropositiva en tratamiento con elvitegravir/cobicistat/emtricitabina/TAF (Genvoya®). Este caso pone de manifiesto la importancia de la revisión de las interacciones entre el tratamiento antirretroviral y otros tratamientos concomitantes, especialmente cuando el esquema antirretroviral contiene inhibidores de proteasa potenciados con ritonavir o cobicistat. Esta potenciación afecta a la ruta metabólica mediada por el citocromo P450. Un elevado número de fármacos son metabolizados por el citocromo P450, y por tanto pueden verse afectados cuando se administran con ritonavir o cobicistat. (AU)

Use of a closed-system drug transfer device (PhaSeal) and impact on preparation time.

PhaSeal is a closed-system drug transfer device which has demonstrated to protect against occupational exposure to antineoplastic agents. Our aim was to assess the impact of the incorporation of PhaSeal on the processing time of chemotherapy. The study was a prospective simulation study which compared the processing times with the traditional open-system technique and using the closed-transfer system. Four experienced pharmacy technicians prepared six batches with each method simulating simple chemotherapy admixture operations. We compared the mean times obtained by student's t test and evaluated the "learning effect" between days by ANOVA. The average percentage of time saving with PhaSeal was 31.7% (time per batch [mean +/- SD] 6.44+0.73 vs. 9.44+0.98 minutes). Mean difference was statistically significant (3.0 min IC95% 2.50-3.50; p>0.0001). No significant learning curve effect was detected. The BD Medical/Carmel Pharma PhaSeal system, in addition to its protective properties, is able to save time in the elaboration process which leads to organization advantages for hospital pharmacy services.

Rod outer segments are designed for optimum photon detection.

The proposal that rod outer segment length is optimal with respect to photon absorption and noise control is extended and tested in a number of species. We find good agreement with our optimality criterion in duplex retinae where rods act as detectors of one or a few photons, but not in all rod retinae nor in those which are exposed to significant photic environmental noise.

A theoretical proposal to account for visual computation in a frog's retina.

Our theoretical account for visual computation in a frog's retina is based on the concepts that: (a) outer retinal layers provide three spatial channels of information pertaining to local spatio-temporal properties of retinal stimuli; (b) prominent specialisation in a frog's retina is the result of a non-linear lateral interaction at the inner plexiform layer; (c) ganglion cell firing frequency is determined by a local computation wherein signals from processes above are either excitatory, facilitatory or defacilitatory. General though concrete expressions for the processing at different layers are developed from these concepts. They result in a unified model for ganglion retinal cells in frog, from which the various extreme groups of ganglia can be deduced. The model leaves a natural margin to fit intermediate types, both found and likely to be found.

A model for non-linear processing in cat's retina.

The model is based on the concept that non-linear lateral interaction at the inner plexiform layer accounts for most of the specialization and marked non-linearities in cat's retinal ganglion cell responses. The inputs to the lateral interaction processes are a spatio-temporal signal and its retarded, as suggested by the behaviour of simple ganglion cells. Lateral interaction in the model consists of lateral linear inhibition followed by local half wave rectification. The resulting signals are weighted and summated by the ganglion cell thereafter. A transparent and general expression is obtained for the response of the cell model which, albeit its simplicity, leads to most of known types of non-linear responses, including the rarely encountered specialized cells in cat's, retina, except colour coding units. For negligible lateral interaction, the model reduces to spatio-temporal linear models under the two paths hypothesis. A discussion of the possible role of anatomical units in these retinal processes in presented, where a general interpretation for visual processing in cat's retina evolves from.

A layered model for visual processing in avian retina.

Visual processing in avian retina is interpreted by means of a layered model in which: a) outer layers provide with spatio temporal fast and retarded versions of the stimuli incident on the retina; a possibility is that horizontal cells are involved in isotropically generating the retarded version which is transversally translated; b) prominent specialization of ganglion cells is the result of local non-linear lateral interaction at the inner plexiform layer, mediated by amacrines which return, also isotropically, the translated retarded signals. Small though systematic deviations in the sites of the lateral interaction result in anisotropic but uniform receptive fields for some ganglion cells. A simple though general expression for the model is derived which includes the various types of recorded avian ganglion retinal cells responses, which also permits a unified interpretation of visual processing in avian and cat's retinae.

Computer programs to implement retinal models.

To implement retinal models of some complexity a set of computer programs, coordinated by a main program is required. A set of said programs is presented here which permits the design and the experimentation with linear and non-linear retinal layered models. A main program, called RETINA, is the basis for the building of a model, the generation of the input stimuli and the experimentation with the overall system.

A theoretical model for layered visual processing.

A theoretical general model of layered computation in the retina is presented. Each layer is functional in the sense that it may correspond or not to an anatomical layer. It is formed by computing elements which can perform in principle any non-linear arbitrary function on a three-dimensional input space. This space consists of 2 spatial dimensions, plus time. The function performed by each computing element of a layer is simplified for the cases of invariance, space or time linearity and for time independence. Two illustrations are also presented. The first is a model of the simple ganglion cells in cat's retina. The second, a model of the group 2 ganglion cell of the frog's retina.