Virologs, viral mimicry, and virocell metabolism: the expanding scale of cellular functions encoded in the complex genomes of giant viruses.

The phylum Nucleocytoviricota includes the largest and most complex viruses known. These "giant viruses" have a long evolutionary history that dates back to the early diversification of eukaryotes, and over time they have evolved elaborate strategies for manipulating the physiology of their hosts during infection. One of the most captivating of these mechanisms involves the use of genes acquired from the host-referred to here as viral homologs or "virologs"-as a means of promoting viral propagation. The best-known examples of these are involved in mimicry, in which viral machinery "imitates" immunomodulatory elements in the vertebrate defense system. But recent findings have highlighted a vast and rapidly expanding array of other virologs that include many genes not typically found in viruses, such as those involved in translation, central carbon metabolism, cytoskeletal structure, nutrient transport, vesicular trafficking, and light harvesting. Unraveling the roles of virologs during infection as well as the evolutionary pathways through which complex functional repertoires are acquired by viruses are important frontiers at the forefront of giant virus research.

Encefalopatía de Hashimoto. Un diagnóstico por exclusión y revisión de la literatura a partir de un reporte de caso / Hashimoto Encephalopathy as Diagnosis by Exclusion Review of the Literature from a Case Report

La encefalopatía de Hashimoto es una entidad poco frecuente, con una amplia gama de manifestaciones neurológicas que incluyen déficits focales, alteraciones cognitivas, crisis convulsivas, trastorno del movimiento e incluso el coma. Con un curso de la enfermedad de subagudo a fluctuante. Afecta más a mujeres que a hombres, con edad de presentación alrededor de los 44 años, aunque se han reportado casos en la edad pediátrica. De etiología poco clara, se desarrolla en el contexto de la presencia de anticuerpos antitiroideos, independientemente de la función tiroidea. La presencia de estos anticuerpos, sumado a la exclusión de otras etiologías y la respuesta al manejo esteroide son claves para su diagnóstico. Presentamos un caso clínico de una mujer de 57 años de edad que evoluciona con psicosis, alteración del lenguaje, deterioro cognitivo, mioclonías y crisis convulsivas de 5 meses de evolución, quien se excluyó otras causas de demencia rápidamente progresiva con presencia de anticuerpos anti tiroglobulina de 83,6 UI/mL (V.R. < 100 UI/mL) normal y anti tiroperoxidasa en 217 UI/mL (V.R. < 100 UI/mL) elevado. Recibió valoración por el Servicio de Endocrinología, donde se detectó hipotiroidismo y se indicó manejo con levotiroxina sin mejoría del cuadro neurológico. Se indicó manejo esteroide con pulsos de metilprednisona a 500 mg/día por 5 días, con mejoría clínica y se concluyó por criterios de exclusión como una encefalopatía de Hashimoto(AU)

Hashimoto encephalopathy is a rare entity, with wide range of neurological manifestations including focal deficits, cognitive alterations, seizures, movement disorders, and even coma, with a subacute to fluctuating disease course. It affects more women than men, it has age of presentation around 44 years, although cases have been reported in the pediatric age. Its etiology is unclear, it develops in the presence of antithyroid antibodies, regardless of thyroid function. The presence of these antibodies, added to the exclusion of other etiologies and the response to steroid management are key to the diagnosis. We report a clinical case of a 57-year-old woman who evolved with psychosis, language impairment, cognitive impairment, myoclonus, and seizures of 5 month-duration. Other causes of rapidly progressive dementia with the presence of normal antithyroglobulin antibodies of 83.6 IU/mL (RV < 100 IU/mL) and elevated antithyroperoxidase 217 IU/mL (RV < 100 IU/mL) were excluded. She was evaluated in the Endocrinology Department that detected hypothyroidism and indicated management with levothyroxine with no improvement in the neurological condition. Steroid management with methylprednisone pulses at 500 mg/day for 5 days was indicated. Clinical improvement was observed and was concluded to be a Hashimoto encephalopathy by exclusion criteria(AU)

Safe and effective re-use policy for high-efficiency filtering facepiece respirators (FFRS): Experience of one hospital during the Covid-19 pandemic in 2020.

The high transmissibility rate of the Severe Acute Respiratory Syndrome Coronavirus 2 facilitated an exponential growth in the number of infections, posing a tremendous threat to healthcare systems across the world. The use of Non-oil 95% efficiency (N95) respirators demonstrated to reduce the risk of virus transmission. The escalated demand in N95 respirators during 2020 generated a massive shortage worldwide which resulted in serious implications, one being an increase in healthcare providers' costs. In response, various optimization strategies were implemented. This study aimed to assess the implementation of a safe and effective re-use policy for high-efficiency filtering facepiece respirators (FFRs) in a high-complexity university hospital in 2020. Associated costs were estimated through a descriptive accounting analysis of resources saved. Acceptability, appropriateness, and feasibility rates were 80.5%, 78.8%, and 83.6%, respectively. With an implementation cost of approximately 10,000 USD, there was a 56.1% reduction in FFRs consumption, compared with a non-policy scenario, with savings exceeding 500,000 USD in 2020. In a pandemic scenario where it is vital to spare resources, a FFRs rational use policy demonstrated to be a highly cost-efficient alternative in order to save resources without increasing contagion risk among healthcare workers.

Esplenomegalia masiva en el curso de reactivación de histoplasmosis diseminada en paciente de sida / Massive splenomegaly in the course of disseminated histoplasmosis reactivation in an AIDS patient

Introducción: La histoplasmosis diseminada es la forma de presentación más frecuente de esta micosis endémica en pacientes de sida. La esplenomegalia consecuente es muy frecuente, pero generalmente no es masiva. Objetivo: Describir un caso no frecuente de esplenomegalia masiva por histoplasmosis diseminada en un paciente de sida. Caso clínico: Se presenta el caso de un paciente de sida diagnosticado hacía 14 años. Desde entonces cumplió tratamiento antirretroviral en forma irregular. Tuvo un primer evento de esta micosis 10 años atrás. En esa ocasión, tuvo tratamiento antimicótico por 4 meses sin continuar con profilaxis secundaria. Inició con síntomas sugestivos de reactivación de la enfermedad 6 meses después. Se mantuvo sintomático en forma recurrente por todos esos años y acudió en fecha actual en estadio avanzado con linfadenopatías grandes y hepatoesplenomegalia masiva. Se confirmó el diagnóstico mediante biopsia ganglionar y se impuso tratamiento antimicótico, con lo cual los síntomas desaparecieron y hubo una reducción ostensible de los órganos que estaban aumentados de tamaño. Conclusión: La esplenomegalia masiva puede presentarse en esta enfermedad. En este caso debe haber sido originada por el largo periodo de reactivación, a su vez determinado por el estado de inmunodepresión oscilante, ya muy avanzado en el momento de su presentación, por la irregularidad del tratamiento antirretroviral y la falta de profilaxis secundaria de la micosis(AU)

Introduction: Disseminated histoplasmosis is the most frequent form of presentation of this endemic mycosis in AIDS patients. Splenomegaly commonly occurs as a consequence of it, but it is not usually massive. Objective: To describe an uncommon case of massive splenomegaly caused by disseminated histoplasmosis in an AIDS patient. Clinical case: The case of an AIDS patient diagnosed 14 years ago is presented. Since diagnosis, the patient has been under antiretroviral treatment irregularly. The first event of this mycosis was 10 years ago. In that occasion, antimitotic treatment was prescribed for four months without secondary prophylaxis. Six months later, symptoms suggestive of reactivation of the disease started. The patient remained symptomatic on a recurrent basis over these years, and attended recently to the hospital in an advanced stage of the disease with large lymphadenopathies and massive hepatosplenomegaly. Diagnostic was confirmed by node biopsy, and antimycotic treatment was indicated, resulting in the resolution of the symptoms and an evident reduction of the enlarged organs. Conclusions: Massive splenomegaly can be present in this disease. In this case, it should have been originated due to a long reactivation period which was determined by the varying and advanced immunosuppressed state, the irregularity with the antiretroviral treatment, and the lack of secondary prophylaxis for the mycosis(AU)

Linfoma cardiaco primario / Primary cardiac lymphoma

Los tumores cardíacos primarios son raros. Tienen una incidencia que varía entre 1,38 y 30 por 100.000 personas al año, un aproximado de 75-80 por ciento son benignos. El linfoma cardíaco primario representa el 1,3 por ciento de los tumores cardíacos primarios y el 0,5 por ciento de los linfomas extranodales. Se define como un linfoma no Hodgkin (LNH) que afecta solo al corazón y/o el pericardio. Su complejo sintomático puede incluir disnea, dolor torácico, fatiga progresiva, sudoración nocturna, pérdida ponderal, arritmias, síndrome de vena cava superior y un aproximado del 20 por ciento de los pacientes pueden desarrollar insuficiencia cardíaca aguda como primera manifestación. Sin embargo, la mayoría de ellos cursan con sintomatología inespecífica y son detectados de manera incidental. El linfoma no Hodgkin difuso de células B grandes es la variante histológica más frecuente. Presentamos un caso que inició con síntomas de insuficiencia cardiaca derecha, evolucionó desfavorable hasta su fallecimiento y se realizó el diagnóstico en la autopsia(AU)

Primary cardiac tumors are rare. They have an incidence that varies between 1.38 and 30 per 100,000 people per year, 75-80 percent are benign, approximately. Primary cardiac lymphoma represents 1.3 percent of primary cardiac tumors and 0.5 percent of extranodal lymphomas. It is defined as a non-Hodgkin's lymphoma (NHL) affecting only the heart and/or the pericardium. Its symptoms may include dyspnea, chest pain, progressive fatigue, night sweats, weight loss, arrhythmias, and superior vena cava syndrome. Approximately 20 percent of patients may develop acute heart failure as the first manifestation. However, most of them have nonspecific symptoms and are detected incidentally. Diffuse large B-cell non-Hodgkin's lymphoma is the most frequent histological variant. We report a case that began with symptoms of right heart failure, progressed unfavorably until death, and the diagnosis was made at autopsy(AU)

COVID-19 response in Colombia: Hits and misses.

Introduction: Colombia has been hit particularly hard by the COVID-19 pandemic, being ranked 22nd among 187 countries in deaths per 100,000 people by February 2022. The country has also experienced the worst economic recession in its history, with real GDP contracting 7% in 2020. This paper describes Colombia's pre-pandemic context and the overall effect of the pandemic on health and economic indicators and examines the government's response to COVID-19. Methods: Descriptive chronologic policy analysis on the COVID-19 pandemic in Colombia and the measures and interventions implemented, using publicly available secondary data from Colombia's official agencies and international sources published from March 2020 to February 2022. Results: The Colombian healthcare system increased its capacity in terms of infrastructure and human resources (from 8.6 ICU beds per 100,000 pre-pandemic to 21.9 in 2020, from 1.7 to 1.3 per 1000 doctors and nurses, respectively in 2019 to 1.8 and 1.5 per 1000 in 2020). The government commenced the National Vaccination Strategy on February 17, 2021, despite a slow start it managed to fully vaccinate 65.1% of its population, including Venezuelan immigrants, by February 2022. Conclusions: Colombia's response to the pandemic combines hits and misses. The country organized an early and robust response; increased its healthcare system capacity; designed a risk-based, equitable, and inclusive national vaccination strategy; and introduced a flexible and responsive vaccine rollout. However, the government chose the wrong timing for reform, implemented a long and unpredictable lockdown, was late to procure COVID-19 vaccines and has not appropriately tackled vaccine hesitancy. Public interest summary: Colombia has been hit particularly hard by the COVID-19 pandemic, with over 138,000 COVID-19 deaths and over 6 million cases by the end of February 2022. According to number of deaths per 100,000 people, Colombia ranks 22nd in the world, among 187 countries. The country has also experienced the worst economic recession in its history. The Colombian healthcare system has been able to cope with a high number of COVID-19 cases without collapsing, but some public health indicators deteriorated. Colombia's response to the pandemic combines hits and misses. The country organized an early and robust response; increased its healthcare system capacity; designed a risk-based, equitable, and inclusive national vaccination strategy; and introduced a flexible and responsive vaccine rollout. As of February 2022, Colombia has fully vaccinated 65.1% of its population. However, the government chose the wrong timing for a tax reform, implemented a long and unpredictable lockdown, was late to procure COVID-19 vaccines and has not appropriately tackled vaccine hesitancy, which certainly contributed to its undesirable position in the mortality world raking.

Uso ambulatorio de cefalosporinas en una población colombiana: estudio de prescripción-indicación / Outpatient cephalosporin use in a Colombian population: prescription-indication study

INTRODUCCIÓN: El uso indebido de cefalosporinas puede provocar resistencia de las bacterias. OBJETIVO: Determinar el perfil de prescripción e indicación de cefalosporinas en un grupo de pacientes afiliados al Sistema de Salud de Colombia. MÉTODOS: Estudio transversal. A partir de una base de datos poblacional se obtuvo una muestra aleatoria de pacientes atendidos en consulta ambulatoria para identificar las indicaciones de cefalosporinas en registros clínicos. Se evaluaron variables farmacológicas relacionadas con formulación no indicada según guías de práctica clínica. RESULTADOS: En 381 pacientes, con edad media 41,2 ± 15,4 años, el 61,4% (n = 234) eran mujeres. Cefalexina fue la más utilizada (n=318; 83,5%), con duración media del tratamiento de 7,3 ± 3,2 días, seguida de cefradina (n = 43, 11,3%) y ceftriaxona (n = 20, 5,2%). Se prescribieron para infecciones de piel y tejidos blandos (n = 177; 46,4%, de las cuales 47,5% eran purulentas), del tracto urinario (n = 70; 18,4%), de vías respiratorias superiores (n = 57; 15,0%), e infecciones de transmisión sexual (n = 21; 5,5%). Estaban indicadas en 169 pacientes (44,4%), pero sólo 103 (60,9%) tenían prescripciones que cumplían las recomendaciones de dosificación. CONCLUSIONES: Más de la mitad de pacientes prescritos con cefalosporinas en un contexto ambulatorio tenían prescripciones consideradas no indicadas, en particular por su uso en infecciones de piel y tejidos blandos purulentas.

BACKGROUND: Misuse of cephalosporins can lead to bacterial resistance. Aim: To determine the prescription profile and indication of cephalosporins in the patients affiliated to the Colombian Health System. METHODS: Cross-sectional study. From a population database, a random sample of patients treated in an outpatient consultation was obtained, to identify the indications of the prescribed cephalosporins in their clinical record. Pharmacological variables, and those related to non-indicated formulations were evaluated according to the clinical practice guidelines. RESULTS: In 381 patients, the mean age was 41.2 ± 15.4 years, and 61.4% (n = 234) were women. Cefalexin was the most widely used (n=318; 83.5%), with a mean duration of treatment of 7.3 ± 3.2 days; followed by cefradine (n = 43; 11.3%), and ceftriaxone (n = 20; 5.2%). The most common uses were for skin and soft tissue infections (n = 177; 46.4% of which 47.5% were purulent), urinary tract infections (n = 70; 18.4%), upper respiratory airway infections (n = 57; 15.0%) and sexually transmitted diseases (n = 21; 5.5%). The use was considered indicated in 169 patients (44.4%), but only 103 (60.9%) had prescriptions that met the dosage recommendations from the clinical practice guidelines. CONCLUSIONS: More than half of the patients prescribed with cephalosporins in the outpatient setting had prescriptions considered not indicated, particularly for their use in purulent skin and soft tissue infections.

Paraneoplastic pemphigus as an atypical presentation of Castleman disease / Pénfigo paraneoplásico como presentación atípica de la enfermedad de Castleman

Abstract Castleman disease is a non-clonal lymphoproliferative disorder with a broad range of clinical manifestations. We present the case of a male patient with a clinical picture of asthenia, adynamia, hyporexia, weight loss, oral and genital ulcers, and red, itchy eyes. The physical exam showed conjunctival redness and oral and genital ulcers. Computed axial tomography with contrast of the chest and abdomen revealed multiple enlarged mediastinal and retroperitoneal lymph nodes, and a solid 94x51 mm retroperitoneal mass. A biopsy of the mass was taken, which reported the hyaline vascular variant of Castleman disease. A scrotal lesion biopsy was also ordered, with a histopathological analysis compatible with pemphigus. In addition, direct immunofluorescence was positive in the epidermal intercelullar spaces, as well as immunoprecipitation with anti-desmoglein, anti-desmoplakin, anti-envoplakin and pemphigoid ampule antigen. Thus, the presence of multicentric Castleman disease associated with paraneoplastic pemphigus was established. (Acta Med Colomb 2021; 46. DOI: https://doi.org/10.36104/amc.2021.1964)

Resumen La enfermedad de Castleman es un trastorno linfoproliferativo no clonal con amplia gama de manifestaciones clínicas. Se presenta el caso de paciente masculino con cuadro clínico consistente en astenia, adinamia, hiporexia, pérdida ponderal, úlceras orales y genitales, prurito ocular e hi peremia conjuntival. El examen físico evidenció hiperemia conjuntival, úlceras orales y genitales. La tomografía axial computarizada contrastada de tórax y abdomen reveló múltiples adenopatías mediastinales, retroperitoneales y masa sólida de 94 x 51 milímetros de localización retroperitoneal. Se realizó biopsia de la masa previamente descrita, que reportó enfermedad de Castleman variante hialino vascular. También se indicó biopsia de lesión escrotal cuyo análisis histopatológico fue compatible con pénfigo, además la fluorescencia inmunológica directa fue positiva en los espacios intercelulares de la epidermis al igual que inmunoprecipitación con anticuerpos anti-desmogleina, anti-desmoplaquina, anti-envoplaquina y antígeno del penfigoide ampollar. Por lo anteriormente descrito se definió la existencia de enfermedad de Castleman multicéntrica asociada a pénfigo paraneoplásico. (Acta Med Colomb 2021; 46. DOI: https://doi.org/10.36104/amc.2021.1964)

[Outpatient cephalosporin use in a Colombian population: prescription-indication study]. / Uso ambulatorio de cefalosporinas en una población colombiana: estudio de prescripción-indicación.

BACKGROUND: Misuse of cephalosporins can lead to bacterial resistance. AIM: To determine the prescription profile and indication of cephalosporins in the patients affiliated to the Colombian Health System. METHODS: Cross-sectional study. From a population database, a random sample of patients treated in an outpatient consultation was obtained, to identify the indications of the prescribed cephalosporins in their clinical record. Pharmacological variables, and those related to non-indicated formulations were evaluated according to the clinical practice guidelines. RESULTS: In 381 patients, the mean age was 41.2 ± 15.4 years, and 61.4% (n = 234) were women. Cefalexin was the most widely used (n=318; 83.5%), with a mean duration of treatment of 7.3 ± 3.2 days; followed by cefradine (n = 43; 11.3%), and ceftriaxone (n = 20; 5.2%). The most common uses were for skin and soft tissue infections (n = 177; 46.4% of which 47.5% were purulent), urinary tract infections (n = 70; 18.4%), upper respiratory airway infections (n = 57; 15.0%) and sexually transmitted diseases (n = 21; 5.5%). The use was considered indicated in 169 patients (44.4%), but only 103 (60.9%) had prescriptions that met the dosage recommendations from the clinical practice guidelines. CONCLUSIONS: More than half of the patients prescribed with cephalosporins in the outpatient setting had prescriptions considered not indicated, particularly for their use in purulent skin and soft tissue infections.

Factores asociados a complicaciones infecciosas posoperatorias en pacientes con urolitiasis / Factors Associated with Postoperative Infectious Complications in Patients with Urolitiasis

Introducción Se encuentran múltiples tratamientos para la urolitiasis, los cuales dependen en gran medida del tamaño y la ubicación de la litiasis. Dentro de las opciones terapéuticas se encuentran la expulsión activa, utilización de ondas de choque, las ureterolitotomias, y procedimientos endoscópicos, todas con diferentes tasas de efectividad y riesgo de complicación infecciosa. El objetivo del estudio fue evaluar los factores asociados a la complicación infecciosa posterior al procedimiento urológico en pacientes con urolitiasis. Métodos Estudio de casos y controles anidado a una cohorte de pacientes programados para procedimientos urológicos como tratamiento para la urolitiasis durante el periodo 2015 - 2019. Se consideraron casos, aquellos con complicación infecciosa posoperatoria dentro de los 30 días posteriores al procedimiento urológico. Los controles se seleccionaron de la cohorte inicial y fueron los pacientes que no presentaron complicación infecciosa. Resultados En el periodo de estudio, fueron atendidos 350 pacientes con litiasis renal, con un total de 1258 cálculos. El número promedio de cálculos por paciente fue de 3,59; la prevalencia de litiasis bilateral fue del 57%, siendo similar la cantidad de cálculos en el lado izquierdo (promedio = 1,4) y en el derecho (promedio = 1,44). La tasa de complicación infecciosa posquirúrgica fue del 4% (n= 14) y se asoció con la presencia de al menos un cálculo mayor de 20 mm (OR 4,49 IC95% 1,39­14,52). Conclusión La tasa de complicación infecciosa posoperatoria en pacientes con urolitiasis y programados para procedimientos urológicos es baja. Una longitud del cálculo mayor de 20 mm es un factor asociado a la infección posoperatoria.

Introduction There are multiple treatments for urolithiasis, which largely depend on the size and location of the lithiasis. Among the therapeutic options are active expulsion, use of shock waves, urolithotomies, and endoscopic procedures, all with different rates of effectiveness and risk of infectious complications. The objective of the study was to evaluate the factors associated with the infectious complication after the urological procedure in patients with urolithiasis. Methods Case-control study nested in a cohort of patients scheduled for urological procedures as treatment for urolithiasis during the period 2015-2019. Cases were considered, those with postoperative infectious complication within 30 days after the urological procedure. The controls were selected from the initial cohort and were the patients who did not present an infectious complication. Results During the study period, 350 patients with kidney stones were treated, with a total of 1258 stones. The average number of stones per patient was 3.59; the prevalence of bilateral lithiasis was 57%, the number of stones being similar on the left side (average = 1.4) and on the right (average = 1.44). The postoperative infectious complication rate was 4% (n = 14) and was associated with the presence of at least one stone larger than 20 mm (OR 4.49 95% CI 1.39 - 14.52). Conclusion The postoperative infectious complication rate in patients with urolithiasis and scheduled for urological procedures is low. A stone length greater than 20 mm is a factor associated with postoperative infection.

Data analysis of incomplete repeated measures using a multivariate extension of the Brown-Forsythe procedure / Análisis de datos de medidas repetidas incompletas usando una extensión multivariante del enfoque de Brown-Forsythe

BACKGROUND: A multivariate extension of the Brown-Forsythe (MBF) procedure can be used for the analysis of partially repeated measure designs (PRMD) when the covariance matrices are arbitrary. However, the MBF procedure requires complete data over time for each subject, which is a significant limitation of this procedure. This article provides the rules for pooling the results obtained after applying the same MBF analysis to each of the imputed datasets of a PRMD. METHOD: Montecarlo methods are used to evaluate the proposed solution (MI-MBF), in terms of control of Type I and Type II errors. For comparative purposes, the MBF analysis based on the complete original dataset (OD-MBF) and the covariance pattern model based on an unstructured matrix (CPM-UN) were studied. RESULTS: Robustness and power results showed that the MI-MBF method performed slightly worse than tests based on CPM-UN when the homogeneity assumption was met, but slightly better when that assumption was not met. We also note that without assuming equality of covariance matrices, little power was sacrificed by using the MI-MBF method in place of the OD-MBF method. CONCLUSIONS: The results of this study suggest that the MI-MBF method performs well and could be of practical use

ANTECEDENTES: para analizar diseños de medidas parcialmente repetidas (DMPR) con matrices de covarianza arbitrarias se puede usar una extensión multivariante del enfoque de Brown-Forsythe (MBF). Una importante limitación de este enfoque es que requiere datos completos para cada sujeto. Este artículo proporciona las reglas para agrupar los resultados obtenidos tras aplicar el análisis MBF a los diferentes conjuntos de datos imputados de un DMPR. MÉTODO: se aplican técnicas de Montecarlo para evaluar la solución propuesta (IM-MBF), en términos de control de los errores Tipo I y Tipo II. Con fines comparativos, también se evalúan los resultados obtenidos con el enfoque MBF basado en los datos originales (DO-MBF), así como con el modelo de patrones de covarianza basado en asumir una matriz no estructurada (MPC-NE). RESULTADOS: cuando se cumple el supuesto de homogeneidad, el desempeño de la prueba IM-MBF es ligeramente inferior al obtenido con la prueba MPC-NE, mientras que sucede lo contrario cuando se incumple dicho supuesto. También encontramos que se pierde poca potencia usando el enfoque MI-MBF, en lugar del enfoque DO-MBF, cuando las matrices de covarianza son heterogéneas. CONCLUSIONES: los resultados sugieren que el enfoque MI-MBF funciona bien y podría ser de uso práctico

Disposición de danofloxacina en plasma y en tejidos comestibles de pollos parrilleros / Disposition of danofloxacin in plasma and edible tissues of broiler chickens / Disposição de danofloxacina em plasma e em tecidos comestíveis de frangos de corte

Resumen Se estudió la disposición de danofloxacina en pollos parrilleros, con el objetivo de establecer parámetros farmacocinéticos en plasma y tejidos y estimar un periodo de retiro. Se dividieron 42 pollos adultos en 14 grupos de 3 individuos cada uno, que recibieron una dosis oral única de 5 mg/kg de danofloxacina, luego de un periodo de ayuno comprendido entre las 12 h previas y las 3 h posteriores a la administración. Cada lote se sacrificó en tiempos preestablecidos, y se obtuvieron muestras de sangre, músculo e hígado en un periodo de hasta 120 h postaplicación. El ensayo consistió en la extracción líquido-líquido del analito, su separación y la cuantificación por cromatografía líquida de alta performance (HPLC). Los promedios de concentración plasmática y tisular por tiempo se analizaron con el programa PK Solution. Mediante el programa WT 1.4 se calculó el periodo de retiro, con base en los límites máximos de residuos (LMR) de 200 y 400 μg/kg, establecidos para músculo e hígado de pollo, respectivamente. La danofloxacina exhibe una rápida absorción, con lo cual logra una Cmáx de 1,1 μg/ml en un Tmáx de 1 h; presenta un t½β (h) de 7,64; 6,16 y 12,77 h en plasma, hígado y músculo, respectivamente; un Vd de 5,51 L/kg; cocientes tejido/plasma de 0,48 y 6,61 en músculo e hígado, respectivamente, y niveles hasta 72 h. Con el análisis de las concentraciones residuales se estima un periodo de resguardo de 1,4 y 3,34 d, para músculo e hígado, respectivamente.

Abstract This paper aimed to study the disposition of danofloxacin in broiler chickens in order to establish pharmacokinetic parameters in plasma and tissues and to estimate a withdrawal period. 42 adult chickens were divided into 14 groups of 3 individuals each, who received a single oral dose of 5 mg/kg of danofloxacin after a fasting period of 12 h before and 3 h post-administration. Each batch was sacrificed at pre-established times, and blood, muscle, and liver samples were obtained over a period of up to 120 h post-application. The assay consisted of the liquid-liquid extraction of analyte and its separation and quantification by high-performance liquid chromatography (HPLC). Time averages for plasma and tissue concentration were analyzed using the PK Solution software. Withdrawal period was calculated using the WT 1.4 program, based on maximum residue limits (MRL) of 200 and 400 μg/kg, established for chicken muscle and liver, respectively. Danofloxacin exhibits a rapid absorption, resulting in a Cmax of 1.1 μg/ml with a Tmax of 1 h; t½β (h) was 7.64; 6.16 and 12.77 in plasma, liver, and muscle, respectively; a Vd of 5.51 L/kg; tissue/plasma ratios of 0.48 and 6.61 in muscle and liver, respectively, and levels up to 72 h. Based on residual concentration analysis, a withdrawal period of 1.4 and 3.34 d was estimated for muscle and liver, respectively.

Resumo Estudou-se a disposição de danofloxacina em frangos de corte, com o objetivo de establecer parâmetros farmacocinéticos em plasma e tecidos e estimar um periodo de retiro. 42 frangos adultos foram divididos em 14 grupos de 3 indivíduos cada um, que receberam uma dose oral única de 5 mg/kg de danofloxacina, depois de um periodo de jejum compreendido entre as 12 horas prévias e as 3 horas posteriores à administração. Cada lote foi sacrificado em tempos pré-estabelecidos, e foram obtidas amostras de sangue, músculo e fígado em um periodo de até 120 horas pós-aplicação. O ensaio consistiu na extração líquido-líquido do analito, sua separação e a quantificação por cromatografía líquida de alta performance (HPLC). As médias de concentração plasmática e tisular por tempo foram analisadas com o programa PK Solution. Mediante o programa WT 1.4 calculou-se o periodo de retiro, com base nos limites máximos de resíduos (LMR) de 200 e 400 μg/kg, estabelecidos para músculo e fígado de frango, respectivamente. A danofloxacina exibe uma rápida absorção, com a qual consegue uma Cmáx de 1,1 μg/ml em um Tmáx de 1 h; apresenta um t½β (h) de 7,64; 6,16 e 12,77 h em plasma, fígado e músculo, respectivamente; um Vd de 5,51 L/kg; cocientes tecido/plasma de 0,48 e 6,61 em músculo e fígado, respectivamente, e níveis até 72 h. Com a análise das concentrações residuais se estima um periodo de resguardo de 1,4 e 3,34 d, para músculo e fígado, respectivamente.

Farmacocinética plasmática y urinaria de marbofloxacina intramuscular en caninos / Plasma and urine pharmacokinetics of intramuscular marbofloxacin in canines / Farmacocinética plasmática e urinária de marbofloxacina intramuscular em caninos

Resumen: Se estudió la disposición plasmática y urinaria de marbofloxacina en caninos (n = 6) tras la aplicación intramuscular de 2 mg/kg. En distintos tiempos posadministración se tomaron muestras de sangre hasta las 24 h, y de orina solo en los caninos machos (n = 4) a las 4, 8, 12 y 24 h. Se realizó una extracción líquido-líquido del analito con agua, metanol y centrifugado a 13.500 r. p. m. a 4 °C. La separación y cuantificación se realizó por HPLC mediante la elusión isocrática en fase reversa, utilizando columna C-18, detector de fluorescencia a 295 nm de excitación y 490 nm de emisión y fase móvil compuesta por agua, acetonitrilo y trietilamina. Las concentraciones plasmáticas temporales se analizaron con el software no compartimental PK Solution 2.0. Los resultados conseguidos indican pronta absorción, rápida y amplia distribución. El Cl y los valores conseguidos de t1/2β y TMR indican lenta depuración y prolongada permanencia. El ensayo determinó concentraciones plasmáticas perdurables hasta 24 h, y que exceden la CMI de patógenos relevantes. El cociente ABC/CMI indica eficacia frente a microorganismos con CMI ≤ 0,15 μg/ml. Las concentraciones urinarias de marbofloxacina son más significativas que las plasmáticas. No obstante, se requieren nuevos estudios que avalen su empleo con la dosis y vía de aplicación ensayada.

Abstract: Plasma and urinary disposition of marbofloxacin was studied in canines (n = 6) after intramuscular administration of 2 mg/kg. At different times post-administration, blood samples were collected until 24 h, and urine samples, only from male dogs (n = 4) at 4; 8; 12, and 24 h. Liquid-liquid extraction of analyte with water, methanol, and centrifugation at 13500 rpm at 4 °C were performed. Separation and quantification were made using HPLC by reverse phase isocratic elution with a C18 column, fluorescence detector at 295 nm excitation and 490 nm emission, and a mobile phase consisting of water, acetonitrile, and triethylamine. Temporary plasma concentrations were analyzed with non-compartmental PK Solution 2.0 software. The results obtained indicate rapid absorption, as well as rapid and wide distribution. Cl and values of t1/2β and MRT indicate slow clearance and prolonged stay. The study evidenced plasma concentrations up to 24 h, which exceed the MIC of relevant pathogens. The AUC/MIC ratio indicates efficacy against microorganisms with MIC ≤ 0.15 μg/ml. Urinary levels of marbofloxacin are more significant than plasmatic levels. However, new studies are required to assess their use with the tested dose and route of application.

Resumo: Se estudou a disposição plasmática e urinária de marbofloxacina em caninos (n = 6) após a aplicação intramuscular de 2 mg/kg. Em diferentes tempos pós-administração se tomaram amostras de sangue hasta as 24 h, e de urina somente nos caninos machos (n = 4) a as 4; 8; 12 e 24 h. Se realizou uma extração líquido-líquido do analito com água, metanol e centrifugado a 13500 r. p. m. a 4 °C. A separação e quantificação se realizou por HPLC mediante a eluição isocrática em fase reversa, utilizando coluna C-18, detector de fluorescencia a 295 nm de excitação e 490 nm de emissão e fase móvel composta por água, acetonitrilo e trietilamina. As concentrações plasmáticas temporárias se analisaram com o software não compartimental PK Solution 2.0. Os resultados conseguidos indicam pronta absorção, rápida e ampla distribuição. O Cl e os valores conseguidos de t1/2β e TMR indicam lenta depuração e prolongada permanência. O ensaio determinou concentrações plasmáticas perduráveis hasta 24 h, e que excedem a CMI de patógenos relevantes. O cociente ABC/CMI indica eficácia frente a micro-organismos com CMI ≤ 0,15 μg/ml. Os níveis urinários de marbofloxacina são mais significativos que os plasmáticos. Não obstante, se requerem novos estudos que avalizem seu uso com a dose e via de aplicação ensaiada.

The role of the open abdomen procedure in managing severe abdominal sepsis: WSES position paper.

The open abdomen (OA) procedure is a significant surgical advance, as part of damage control techniques in severe abdominal trauma. Its application can be adapted to the advantage of patients with severe abdominal sepsis, however its precise role in these patients is still not clear. In severe abdominal sepsis the OA may allow early identification and draining of any residual infection, control any persistent source of infection, and remove more effectively infected or cytokine-loaded peritoneal fluid, preventing abdominal compartment syndrome and deferring definitive intervention and anastomosis until the patient is appropriately resuscitated and hemodynamically stable and thus better able to heal. However, the OA may require multiple returns to the operating room and may be associated with significant complications, including enteroatmospheric fistulas, loss of abdominal wall domain and large hernias. Surgeons should be aware of the pathophysiology of severe intra-abdominal sepsis and always keep in mind the option of using open abdomen to be able to use it in the right patient at the right time.

Multilevel bootstrap analysis with assumptions violated / Análisis bootstrap multinivel con supuestos incumplidos

Background: Likelihood-based methods can work poorly when the residuals are not normally distributed and the variances across clusters are heterogeneous. Method: The performance of two estimation methods, the non-parametric residual bootstrap (RB) and the restricted maximum likelihood (REML) for fitting multilevel models are compared through simulation studies in terms of bias, coverage, and precision. Results: We find that (a) both methods produce unbiased estimates of the fixed parameters, but biased estimates of the random parameters, although the REML was more prone to give biased estimates for the variance components; (b) the RB method yields substantial reductions in the difference between nominal and actual confidence interval coverage, compared with the REML method; and (c) for the square root of the mean squared error (RMSE) of the fixed effects, the RB method performed slightly better than the REML method. For the variance components, however, the RB method did not offer a systematic improvement over the REML method in terms of RMSE. Conclusions: It can be stated that the RB method is, in general, superior to the REML method with violated assumptions (AU)

Antecedentes: los métodos basados en la verosimilitud pueden trabajar con dificultad cuando los errores no se distribuyen normalmente y las varianzas a través de los grupos son heterogéneas. Método: el desempeño de dos métodos de estimación, el bootstrap residual (BR) no paramétrico y el de la máxima verosimilitud restringida (MVR), para ajustar modelos multinivel es comparado mediante estudios de simulación en términos de sesgo, cobertura y precisión. Resultados: encontramos que: (a) ambos métodos proporcionan estimaciones no sesgadas de los efectos fijos, pero sesgadas de los efectos aleatorios, aunque el método MVR es más propenso a generar estimaciones sesgadas para los componentes de la varianza; (b) el método BR depara diferencias más pequeñas entre las tasas de cobertura real y nominal de los intervalos de confianza que el método MVR; y (c) los valores de la raíz del error cuadrático medio (RECM) para los efectos fijos son algo más pequeños bajo el método BR que bajo el método REML. Sin embargo, en lo referido a los componentes de la varianza, el método de BR no ofrece una mejora sistemática sobre el método MVR en términos de RECM. Conclusiones: en general, se puede afirmar que el método BR resulta superior al método MVR con supuestos incumplidos (AU)