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Information regarding the efficacy of the recombinant adenovirus type-5-vectored (CanSino Bio) vaccine against the COVID-19 disease in a real-life setting is limited. A retrospective cohort study was carried out in the teaching university community of the metropolitan area of Monterrey, Mexico, through a four-section survey, and during the COVID-19 delta wave. Determination of IgG antibodies against SARS-CoV-2 spike (S) protein was performed in a subset of participants vaccinated with CanSino Bio. A total of 7468 teachers responded to the survey, and 6695 of them were fully vaccinated. Of those, 72.7% had CanSino Bio, 10.3% Pfizer, 8.4% AstraZeneca, 1.2% Moderna, and 2.7% others. Symptomatic breakthrough infections were recorded in those vaccinated with CanSino Bio (4.1%), AstraZeneca (2.1%), and Pfizer (2.2%). No difference was found between CanSino Bio and other vaccines regarding hospitalization, the need for mechanical ventilation, and death. For CanSino Bio recipients, anti-S antibodies were >50 AU/mL in 73.2%. In conclusion, primary breakthrough symptomatic infections were higher in the CanSino vaccinated group compared to other brands. Individuals with a previous infection had higher antibody levels than those who were reinfected and without infection. A boosted dose of CanSino is recommended for those individuals without a previous infection.
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OBJECTIVE: Firearm violence has a high economic impact, representing the third most expensive injury and associated with the fourth highest hospitalisation cost. This study was performed to determine the clinical and epidemiological characteristics of patients with injuries due to firearm projectile during a period of increased violence related to organised crime in our country. METHODS: A retrospective study (2010-2017) was conducted to analyse the clinical data of patients admitted due to firearm projectile injury. Clinical and epidemiological characteristics of each patient were recorded, and patients were stratified by sex and age. Compared low-energy versus high-energy gunshot injuries, complications and treatment. RESULTS: A total of 1309 gunshot wounds in appendicular skeleton and spine fractures. The mean age of the patients was 29±11.5 years. Upper extremities wounds in 358 cases, lower extremities wounds in 727 cases and 224 fractures in spine region. There were no significant differences between low-velocity and high-velocity projectiles in anatomic affected region, complications and treatment. CONCLUSIONS: We concluded that firearm projectiles cause a variety of injuries both in soft and bone tissues and caused a major rate of complications in our patients even with low- or high-energy weapons. The majority of patients affected were the civilian population. Most patients with gunshot wounds were young males. We observed a low mortality rate in our patients. LEVEL OF EVIDENCE: III; retrospective cohort study.
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Fracturas Óseas , Heridas por Arma de Fuego , Adolescente , Adulto , Fracturas Óseas/complicaciones , Hospitalización , Humanos , Masculino , Estudios Retrospectivos , Violencia , Heridas por Arma de Fuego/complicaciones , Heridas por Arma de Fuego/epidemiología , Adulto JovenRESUMEN
INTRODUCCIÓN: Un trauma penetrante puede dañar una variedad de órganos. Dado que el hígado es un órgano sólido inelástico, no tiene la tolerancia al estiramiento necesaria para hacer frente a una herida por proyectil de arma de fuego (GSW). MÉTODOS: Este fue un estudio retrospectivo, observacional y descriptivo de 53 registros clínicos de pacientes ingresados en el Departamento de Cirugía por trauma hepático (LT) por un GSW. RESULTADOS: Del total de historias clínicas analizadas, el 89% de los pacientes presentaron una lesión asociada con LT. La lesión orgánica asociada más frecuente fue la torácica, específicamente la lesión pulmonar, en el 58%. El predictor más importante de mortalidad fue una estancia en la unidad de cuidados intensivos (UCI), que aumentó el riesgo unas 21 veces. CONCLUSIÓN: Una estadía en la UCI, seguida de la presencia de fracturas, fue el predictor más importante de mortalidad. Se necesitan nuevas medidas de pronóstico para contrarrestar las variables que ha creado el aumento de GSW, además de disminuir el tiempo de espera desde el evento traumático hasta el tratamiento relevante. INTRODUCTION: A penetrating trauma can damage a variety of organs. Since the liver is an inelastic solid organ, it does not have the necessary stretch tolerance to cope with a gunshot wound (GSW). METHODS: This was a retrospective, observational, and descriptive study of 53 clinical records of patients admitted to the Department of Surgery for liver trauma (LT) by a GSW. RESULTS: Of the total clinical records analyzed, 89% of the patients presented a lesion associated with LT. The most common associated organic lesion was thoracic, specifically lung injury, in 58%. The most important predictor of mortality was a stay in the intensive care unit (ICU), which increased the risk about 21 times. CONCLUSION: A stay in the ICU, followed by the presence of fractures, was the most important predictor of mortality. New prognostic measures are needed to counteract the variables that the increase in GSWs has created, in addition to decreasing the waiting time from the traumatic event to relevant treatment.
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Heridas por Arma de Fuego , Humanos , Unidades de Cuidados Intensivos , Hígado/cirugía , Estudios Retrospectivos , Heridas por Arma de Fuego/cirugíaAsunto(s)
COVID-19 , Infecciones del Sistema Respiratorio , Cara , Humanos , SARS-CoV-2 , Salas de EsperaRESUMEN
BACKGROUND: Ischemia-reperfusion (IR) injury is the main cause of delayed graft function in solid organ transplantation. Hypoxia-inducible factors (HIFs) control the expression of genes related to preconditioning against IR injury. During normoxia, HIF-α subunits are marked for degradation by the egg-laying defective nine homolog (EGLN) family of prolyl-4-hydroxylases. The inhibition of EGLN stabilizes HIFs and protects against IR injury. The aim of this study was to determine whether the EGLN inhibitors sodium (S)-2-hydroxyglutarate [(S)-2HG] and succinic acid (SA) have a nephroprotective effect against renal IR injury in Wistar rats. METHODS: (S)-2HG was synthesized in a 22.96% yield from commercially available L-glutamic acid in a two-step methodology (diazotization/alkaline hydrolysis), and its structure was confirmed by nuclear magnetic resonance and polarimetry. SA was acquired commercially. (S)-2HG and SA were independently evaluated in male and female Wistar rats respectively after renal IR injury. Rats were divided into the following groups: sham (SH), nontoxicity [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg], IR, and compound+IR [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg]; independent SH and IR groups were used for each assessed compound. Markers of kidney injury (BUN, creatinine, glucose, and uric acid) and liver function (ALT, AST, ALP, LDH, serum proteins, and albumin), proinflammatory cytokines (IL-1ß, IL-6, and TNF-α), oxidative stress biomarkers (malondialdehyde and superoxide dismutase), and histological parameters (tubular necrosis, acidophilic casts, and vascular congestion) were assessed. Tissue HIF-1α was measured by ELISA and Western blot, and the expression of Hmox1 was assessed by RT-qPCR. RESULTS: (S)-2HG had a dose-dependent nephroprotective effect, as evidenced by a significant reduction in the changes in the BUN, creatinine, ALP, AST, and LDH levels compared with the IR group. Tissue HIF-1α was only increased in the IR group compared to SH; however, (S)-2HG caused a significant increase in the expression of Hmox1, suggesting an early accumulation of HIF-1α in the (S)-2HG-treated groups. There were no significant effects on the other biomarkers. SA did not show a nephroprotective effect; the only changes were a decrease in creatinine level at 12.5 mg/kg and increased IR injury at 50 mg/kg. There were no effects on the other biochemical, proinflammatory, or oxidative stress biomarkers. CONCLUSION: None of the compounds were hepatotoxic at the tested doses. (S)-2HG showed a dose-dependent nephroprotective effect at the evaluated doses, which involved an increase in the expression of Hmox1, suggesting stabilization of HIF-1α. SA did not show a nephroprotective effect but tended to increase IR injury when given at high doses.
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INTRODUCTION: Essential amino acid α-keto acid analogs are used in the treatment of chronic kidney disease to delay the symptoms of uremia. However, it is unknown whether essential amino acid α-keto acid analogs affect the oxidative stress and the inflammation in acute renal injury such as those produced by ischemia-reperfusion. OBJECTIVE: To evaluate the effect of essential amino acid α-keto acid analogs on renal ischemia-reperfusion injury in Wistar rats. MATERIALS AND METHODS: Rats were divided into 11 groups (n=6/group): Two groups received physiological saline with or without ischemia-reperfusion injury (45 min/24 h), six groups received essential amino acid α-keto acid analogs (400, 800, or 1,200 mg/kg/24 h/7d) with or without ischemia-reperfusion injury (essential amino acid α-keto acid analogs + ischemia-reperfusion), and two groups received allopurinol (50 mg/kg/24 h/7d) with or without ischemia-reperfusion injury. Biochemical markers included creatinine and blood urea nitrogen (BUN), proinflammatory cytokines (IL-1ß, IL-6, and TNF-α), renal damage markers (cystatin C, KIM-1, and NGAL), and markers of oxidative stress such as malondialdehyde (MDA) and total antioxidant activity. RESULTS: The essential amino acid α-keto acid analog- and allopurinol-treated groups had lower levels of creatinine, BUN, renal damage markers, proinflammatory cytokines, and MDA than their corresponding ischemia-reperfusion groups. These changes were related to the essential amino acid α-keto acid analogs dosage. Total antioxidant activity was lower in essential amino acid α-keto acid analog- and allopurinol-treated groups than in the corresponding ischemia-reperfusion groups. CONCLUSIONS: This is a new report on the nephroprotective effects of essential amino acid α-keto acid analogs against ischemia-reperfusion injury. Essential amino acid α-keto acid analogs decreased the levels of biochemical markers, kidney injury markers, proinflammatory cytokines, and MDA while minimizing total antioxidant consumption.
Introducción. Los α-cetoanálogos de aminoácidos esenciales se utilizan en el tratamiento de la enfermedad renal crónica para retrasar los síntomas de la uremia. Sin embargo, se desconoce si los α-cetoanálogos de aminoácidos esenciales afectan el estrés oxidativo y la inflamación en la lesión renal aguda tal como en la producida por la isquemia-reperfusión. Objetivo. Evaluar el efecto de las α-cetoanálogos de aminoácidos esenciales sobre la lesión renal por isquemia-reperfusión en ratas Wistar. Materiales y métodos. Se emplearon 11 grupos de ratas (n=6): dos grupos recibieron solución salina fisiológica con lesión isquemia-reperfusión o sin ella (45 min/24 h), seis grupos recibieron α-cetoanálogos de aminoácidos esenciales (400, 800 o 1.200 mg/kg/24 h/7d) con lesión isquemia-reperfusión o sin ella (α-cetoanálogos de aminoácidos esenciales + isquemia-reperfusión), y dos grupos recibieron (50 mg/kg/24 h/7d) con lesión isquemia-reperfusión o sin ella. Los marcadores bioquímicos incluyeron creatinina y nitrógeno ureico en sangre (BUN), citocinas proinflamatorias (IL-1ß, IL-6 y TNF-α), marcadores de daño renal (cistatina C, KIM-1 y NGAL) y marcadores del estrés oxidativo como el malondialdehído (MDA) y la actividad antioxidante total. Resultados. Los grupos tratados con α-cetoanálogos de aminoácidos esenciales y alopurinol tuvieron niveles inferiores de creatinina, BUN, marcadores de daño renal, citocinas proinflamatorias, actividad antioxidante total y MDA que los grupos isquemia-reperfusión correspondientes. Estos cambios se asociaron con la dosis. La actividad antioxidante total fue menor en los grupos tratados con α-cetoanálogos de aminoácidos esenciales que en los grupos isquemia-reperfusión correspondientes. Conclusiones. Este es un nuevo informe de los efectos nefroprotectores de las α-cetoanálogos de aminoácidos esenciales contra la lesión isquemia-reperfusión. Los α-cetoanálogos de aminoácidos esenciales disminuyeron los niveles de los marcadores bioquímicos, de los de lesión renal, de las citocinas proinflamatorias y el MDA, a la vez que minimizaron el consumo total de antioxidantes.
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Aminoácidos Esenciales/uso terapéutico , Antioxidantes/uso terapéutico , Cetoácidos/uso terapéutico , Riñón/irrigación sanguínea , Daño por Reperfusión/tratamiento farmacológico , Alopurinol/uso terapéutico , Aminoácidos Esenciales/administración & dosificación , Animales , Antioxidantes/análisis , Biomarcadores , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Cistatina C/sangre , Citocinas/sangre , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Cetoácidos/administración & dosificación , Riñón/patología , Lipocalina 2/sangre , Masculino , Malondialdehído/sangre , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas Wistar , Daño por Reperfusión/sangre , Daño por Reperfusión/patología , Daño por Reperfusión/prevención & controlRESUMEN
Introduction: Essential amino acid α-keto acid analogs are used in the treatment of chronic kidney disease to delay the symptoms of uremia. However, it is unknown whether essential amino acid α-keto acid analogs affect the oxidative stress and the inflammation in acute renal injury such as those produced by ischemia-reperfusion. Objective: To evaluate the effect of essential amino acid α-keto acid analogs on renal ischemia-reperfusion injury in Wistar rats. Materials and methods: Rats were divided into 11 groups (n=6/group): Two groups received physiological saline with or without ischemia-reperfusion injury (45 min/24 h), six groups received essential amino acid α-keto acid analogs (400, 800, or 1,200 mg/kg/24 h/7d) with or without ischemia-reperfusion injury (essential amino acid α-keto acid analogs + ischemia-reperfusion), and two groups received allopurinol (50 mg/kg/24 h/7d) with or without ischemia-reperfusion injury. Biochemical markers included creatinine and blood urea nitrogen (BUN), proinflammatory cytokines (IL-1ß, IL-6, and TNF-α), renal damage markers (cystatin C, KIM-1, and NGAL), and markers of oxidative stress such as malondialdehyde (MDA) and total antioxidant activity. Results: The essential amino acid α-keto acid analog- and allopurinol-treated groups had lower levels of creatinine, BUN, renal damage markers, proinflammatory cytokines, and MDA than their corresponding ischemia-reperfusion groups. These changes were related to the essential amino acid α-keto acid analogs dosage. Total antioxidant activity was lower in essential amino acid α-keto acid analog- and allopurinol-treated groups than in the corresponding ischemia-reperfusion groups. Conclusions: This is a new report on the nephroprotective effects of essential amino acid α-keto acid analogs against ischemia-reperfusion injury. Essential amino acid α-keto acid analogs decreased the levels of biochemical markers, kidney injury markers, proinflammatory cytokines, and MDA while minimizing total antioxidant consumption.
Introducción. Los α-cetoanálogos de aminoácidos esenciales se utilizan en el tratamiento de la enfermedad renal crónica para retrasar los síntomas de la uremia. Sin embargo, se desconoce si los α-cetoanálogos de aminoácidos esenciales afectan el estrés oxidativo y la inflamación en la lesión renal aguda tal como en la producida por la isquemia-reperfusión. Objetivo. Evaluar el efecto de las α-cetoanálogos de aminoácidos esenciales sobre la lesión renal por isquemia-reperfusión en ratas Wistar. Materiales y métodos. Se emplearon 11 grupos de ratas (n=6): dos grupos recibieron solución salina fisiológica con lesión isquemia-reperfusión o sin ella (45 min/24 h), seis grupos recibieron α-cetoanálogos de aminoácidos esenciales (400, 800 o 1.200 mg/kg/24 h/7d) con lesión isquemia-reperfusión o sin ella (α-cetoanálogos de aminoácidos esenciales + isquemia-reperfusión), y dos grupos recibieron (50 mg/kg/24 h/7d) con lesión isquemia-reperfusión o sin ella. Los marcadores bioquímicos incluyeron creatinina y nitrógeno ureico en sangre (BUN), citocinas proinflamatorias (IL-1ß, IL-6 y TNF-α), marcadores de daño renal (cistatina C, KIM-1 y NGAL) y marcadores del estrés oxidativo como el malondialdehído (MDA) y la actividad antioxidante total. Resultados. Los grupos tratados con α-cetoanálogos de aminoácidos esenciales y alopurinol tuvieron niveles inferiores de creatinina, BUN, marcadores de daño renal, citocinas proinflamatorias, actividad antioxidante total y MDA que los grupos isquemia-reperfusión correspondientes. Estos cambios se asociaron con la dosis. La actividad antioxidante total fue menor en los grupos tratados con α-cetoanálogos de aminoácidos esenciales que en los grupos isquemia-reperfusión correspondientes. Conclusiones. Este es un nuevo informe de los efectos nefroprotectores de las α-cetoanálogos de aminoácidos esenciales contra la lesión isquemia-reperfusión. Los α-cetoanálogos de aminoácidos esenciales disminuyeron los niveles de los marcadores bioquímicos, de los de lesión renal, de las citocinas proinflamatorias y el MDA, a la vez que minimizaron el consumo total de antioxidantes.
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Isquemia , Daño por Reperfusión , Estrés Oxidativo , Insuficiencia Renal Crónica , Inflamación , Modelos TeóricosRESUMEN
BACKGROUND: The wounds caused by the firearm projectile are published to date in a public health problem in the world. As an example, we mentioned the injuries caused by firearms are the first cause of death in the age group between 1 to 19 years in the United States, as in Mexico. OBJECTIVE: Analysis of the prognostic factors of mortality and evaluation of the evolution in patients with TPD due to abdominal HPPAF. METHOD: Retrospective, observational, descriptive study. Helped by 49 clinical files of patients who were admitted to the department of surgery of the University Hospital José Eleuterio González, between 2011 to 2015 and whose diagnosis was due to pancreatic trauma (TP), duodenal trauma (TD) or pancreatoduodenal trauma (TPD) by wounds caused by the firearm projectile. RESULTS: During a collection period of 5 years, a total of 49 clinical records applicable to the study were obtained according to the inclusion criteria, of which 36 (73%) suffered only from TD, 37 (75%) from TP and 24 (49%) about TPD. Significant differences were obtained for mortality associated with TD and TPD, but not for TP. The most affected organ as a lesion associated with a TPD was the liver, followed by thoracic structures and the stomach. The most significant risk factor for mortality was a prolonged stay in the intensive care unit. CONCLUSIONS: Data obtained are consistent with those consulted, providing new reproducible statistics for future studies regarding the increasing violence in our country and around the world.
ANTECEDENTES: Las heridas por proyectil de arma de fuego constituyen un problema de salud pública en el mundo. Como ejemplo mencionamos que este tipo de lesiones son la primera causa de muerte en el grupo de edad de 1 a 19 años en los EE.UU., al igual que en México. OBJETIVO: Análisis de los factores pronósticos de mortalidad y evaluación de la evolución en pacientes con TPD por HPPAF abdominal. MÉTODO: Estudio retrospectivo, observacional y descriptivo, realizado con 49 expedientes clínicos de pacientes que fueron admitidos en el departamento de cirugía del Hospital Universitario José Eleuterio González entre los años 2011 y 2015, cuyo diagnostico fue herida por proyectil de arma de fuego con trauma pancreático (TP), duodenal (TD) o pancreatoduodenal (TPD). RESULTADOS: Durante un periodo de recolección de 5 años se obtuvieron 49 expedientes clínicos aplicables al estudio según los criterios de inclusión, de los cuales 36 pacientes (73%) sufrieron únicamente TD, 37 (75%) TP y 24 (49%) TPD. Se obtuvieron diferencias significativas para la mortalidad asociada a TD y TPD, pero no para TP. El órgano más afectado como lesión asociada a un TPD fue el hígado, seguido de las estructuras torácicas y el estómago. El factor de riesgo para mortalidad más significativo fue una estancia prolongada en la unidad de cuidados intensivos. CONCLUSIONES: Los datos conseguidos concuerdan con los consultados, otorgando nueva estadística reproducible para futuros estudios respecto a la violencia creciente en nuestro país y alrededor del mundo.
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Duodeno/lesiones , Páncreas/lesiones , Heridas por Arma de Fuego/mortalidad , Femenino , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Hígado/lesiones , Masculino , Pronóstico , Estudios Retrospectivos , Estómago/lesiones , Traumatismos TorácicosRESUMEN
Objective: Oral antiplatelet drugs are a key to modern pharmacotherapy in cardiovascular atherothrombotic diseases. Clopidogrel (CLO) constitutes the main preventive treatment of atherothrombosis. However, a considerable inter-individual variation in CLO response has been documented, resulting in suboptimal therapy and an increased risk of recurrent adverse effects in some patients. The enzyme CYP2C19 has been reported to be the CYP isoform that activates CLO to its active metabolite. Several single nucleotide polymorphisms in the CYP2C19 gene have been identified as strong predictors of CLO-impaired pharmacological response. At least 16 variants have been associated with changes in CYP2C19 activity. Materials and Methods: The following research was composed of a total of 102 subjects with high cardiovascular risk in the northeast of Mexico, with a maintenance dose of 75 mg of CLO per day. The platelet reactivity was measured with VerifyNow P2Y12 assay, while the presence of CYP2C19*2 was identified by real-time polymerase chain reaction. Results: Patients were categorized by CYP2C19 metabolizer status based on *2 genotypes using the common consensus star allele nomenclature as normal metabolizer (G/G), intermediate metabolizer (G/A), and poor metabolizer (A/A), respectively. The phenotype frequency for CYP2C19*2 was 74.5% (G/G), 21.6% (G/A), and 3.9% (A/A). The subjects with the A allele presented ≥235 P2Y12 reaction unit levels, classifying them how poor metabolizer. The prevalence of reduced CLO effectiveness was associated with the presence of CYP2C19*2 polymorphism among Mexican patients. Conclusion: The presence of the CYP2C19*2 allele is related to resistance to the antiplatelet effect of CLO (p = 0.003).
Objetivo: Los antiplaquetarios orales son clave en la farmacoterapia moderna de las enfermedades aterotrombóticas cardiovasculares. Clopidogrel (CLO) constituye el principal tratamiento preventivo de aterotrombosis (AT). Sin embargo, se ha documentado una considerable variación interindividual en la respuesta a CLO, lo que da como resultado una terapia subóptima y mayor riesgo de efectos adversos en algunos pacientes. La enzima CYP2C19 es la isoforma CYP que activa CLO a su metabolito activo. Se han identificado varios polimorfismos de un solo nucleótido en el gen CYP2C19 como fuertes predictores de respuesta farmacológica alterada a CLO. Al menos 16 variantes se han asociado con cambios en la actividad de CYP2C19. Método: Se reclutaron un total de 102 sujetos con alto riesgo cardiovascular del noreste de México, con dosis de mantenimiento de 75 mg de CLO/día. La reactividad plaquetaria se midió con el ensayo Verify Now P2Y12, la presencia de CYP2C19*2 se identificó mediante polymerase chain reaction en tiempo real. Resultado: Los pacientes fueron clasificados por el estado metabolizador CYP2C19*2 utilizando nomenclatura consenso, como metabolizador normal (G/G), metabolizador intermedio (G/A) y metabolizador pobre (A/A), respectivamente. La frecuencia del fenotipo para CYP2C19*2 fue 74.5% (G/G), 21.6% (G/A) y 3.9% (A/A). Los sujetos con alelo A presentaron ≥235 niveles P2Y12 reaction unit, clasificándolos como metabolizadores deficientes. La prevalencia de eficacia reducida a CLO se asoció con la presencia del polimorfismo CYP2C19*2 en pacientes mexicanos. Conclusiones: La presencia del alelo CYP2C19*2 se relaciona con resistencia al efecto antiagregante plaquetario del CLO (p = 0.003).
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Enfermedades Cardiovasculares/tratamiento farmacológico , Clopidogrel/administración & dosificación , Citocromo P-450 CYP2C19/genética , Inhibidores de Agregación Plaquetaria/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Enfermedades Cardiovasculares/fisiopatología , Clopidogrel/farmacología , Resistencia a Medicamentos/genética , Femenino , Humanos , Masculino , México , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/farmacología , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
abstract Objective: Oral antiplatelet drugs are a key to modern pharmacotherapy in cardiovascular atherothrombotic diseases. Clopidogrel (CLO) constitutes the main preventive treatment of atherothrombosis. However, a considerable inter-individual variation in CLO response has been documented, resulting in suboptimal therapy and an increased risk of recurrent adverse effects in some patients. The enzyme CYP2C19 has been reported to be the CYP isoform that activates CLO to its active metabolite. Several single nucleotide polymorphisms in the CYP2C19 gene have been identified as strong predictors of CLO-impaired pharmacological response. At least 16 variants have been associated with changes in CYP2C19 activity. Materials and Methods: The following research was composed of a total of 102 subjects with high cardiovascular risk in the northeast of Mexico, with a maintenance dose of 75 mg of CLO per day. The platelet reactivity was measured with VerifyNow P2Y12 assay, while the presence of CYP2C19*2 was identified by real-time polymerase chain reaction. Results: Patients were categorized by CYP2C19 metabolizer status based on *2 genotypes using the common consensus star allele nomenclature as normal metabolizer (G/G), intermediate metabolizer (G/A), and poor metabolizer (A/A), respectively. The phenotype frequency for CYP2C19*2 was 74.5% (G/G), 21.6% (G/A), and 3.9% (A/A). The subjects with the A allele presented ≥235 P2Y12 reaction unit levels, classifying them how poor metabolizer. The prevalence of reduced CLO effectiveness was associated with the presence of CYP2C19*2 polymorphism among Mexican patients. Conclusion: The presence of the CYP2C19*2 allele is related to resistance to the antiplatelet effect of CLO (p = 0.003).
Resumen Objetivo: Los antiplaquetarios orales son clave en la farmacoterapia moderna de las enfermedades aterotrombóticas cardiovasculares. Clopidogrel (CLO) constituye el principal tratamiento preventivo de aterotrombosis (AT). Sin embargo, se ha documentado una considerable variación interindividual en la respuesta a CLO, lo que da como resultado una terapia subóptima y mayor riesgo de efectos adversos en algunos pacientes. La enzima CYP2C19 es la isoforma CYP que activa CLO a su metabolito activo. Se han identificado varios polimorfismos de un solo nucleótido en el gen CYP2C19 como fuertes predictores de respuesta farmacológica alterada a CLO. Al menos 16 variantes se han asociado con cambios en la actividad de CYP2C19. Método: Se reclutaron un total de 102 sujetos con alto riesgo cardiovascular del noreste de México, con dosis de mantenimiento de 75 mg de CLO/día. La reactividad plaquetaria se midió con el ensayo Verify Now P2Y12, la presencia de CYP2C19*2 se identificó mediante polymerase chain reaction en tiempo real. Resultado: Los pacientes fueron clasificados por el estado metabolizador CYP2C19*2 utilizando nomenclatura consenso, como metabolizador normal (G/G), metabolizador intermedio (G/A) y metabolizador pobre (A/A), respectivamente. La frecuencia del fenotipo para CYP2C19*2 fue 74.5% (G/G), 21.6% (G/A) y 3.9% (A/A). Los sujetos con alelo A presentaron ≥235 niveles P2Y12 reaction unit, clasificándolos como metabolizadores deficientes. La prevalencia de eficacia reducida a CLO se asoció con la presencia del polimorfismo CYP2C19*2 en pacientes mexicanos. Conclusiones: La presencia del alelo CYP2C19*2 se relaciona con resistencia al efecto antiagregante plaquetario del CLO (p = 0.003).
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Inhibidores de Agregación Plaquetaria/administración & dosificación , Enfermedades Cardiovasculares/tratamiento farmacológico , Citocromo P-450 CYP2C19/genética , Clopidogrel/administración & dosificación , Resistencia a Medicamentos/genética , Inhibidores de Agregación Plaquetaria/farmacología , Enfermedades Cardiovasculares/fisiopatología , Factores de Riesgo , Polimorfismo de Nucleótido Simple , Alelos , Clopidogrel/farmacología , MéxicoRESUMEN
The amount of irreparable DNA damage is a function of the rate of cell division, and the association between sex hormones and the risk of breast cancer has been explained by an increase in cell division. Folate intake insufficiency leads to disturbances in DNA replication and DNA repair. We hypothesized that folate intake insufficiency and high serum concentrations of sex hormones act synergistically on the risk of breast cancer. The aim of this study was to investigate the interaction between sex hormones (exposure of interest A) and dietary folate intake (exposure of interest B) on the risk of breast cancer. We included 342 breast cancer primary postmenopausal cases and 294 controls obtained from a large population-based case-control study. Multiple conditional logistic regression models were used for the analysis and interactions were tested. The joint effect of the lowest dietary folate intake (T1 <â¯259.40â¯mg/d) and the highest serum concentration of testosterone (T3â¯≥â¯0.410 on the risk of breast cancer was odds ratioâ¯=â¯9.18 (95% confidence interval 2.56-32.88) when compared to the lowest-risk category, namely, the group of women with the highest dietary folate intake (T3 >â¯381.29â¯mg/d) and the lowest serum concentration of testosterone (T1â¯≤â¯0.25â¯pg/mL). There were some indications that the estimated join effect was greater than the product of the estimated effects alone (Pâ¯=â¯.001). These findings have important public health implications with respect to reducing the risk of the most frequent cancer in women worldwide.
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Neoplasias de la Mama/sangre , Neoplasias de la Mama/epidemiología , Dieta/métodos , Ácido Fólico/farmacología , Testosterona/sangre , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Ácido Fólico/administración & dosificación , Ácido Fólico/sangre , Humanos , México/epidemiología , Persona de Mediana Edad , RiesgoRESUMEN
BACKGROUND: Renal diseases represent a major public health problem. The demonstration that maladaptive repair of acute kidney injury (AKI) can lead to the development of chronic kidney disease (CKD) and end-stage renal disease has generated interest in studying the pathophysiological pathways involved. Animal models of AKI-CKD transition represent important tools to study this pathology. We hypothesized that the administration of multiple doses of folic acid (FA) would lead to a progressive loss of renal function that could be characterized through biochemical parameters, histological classification and nuclear magnetic resonance (NMR) profiling. METHODS: Wistar rats were divided into groups: the control group received a daily intraperitoneal (I.P.) injection of double-distilled water, the experimental group received a daily I.P. injection of FA (250 mg kg body weight-1). Disease was classified according to blood urea nitrogen level: mild (40-80 mg dL-1), moderate (100-200 mg dL-1) and severe (>200 mg dL-1). We analyzed through biochemical parameters, histological classification and NMR profiling. RESULTS: Biochemical markers, pro-inflammatory cytokines and kidney injury biomarkers differed significantly (P < 0.05) between control and experimental groups. Histology revealed that as damage progressed, the degree of tubular injury increased, and the inflammatory infiltrate was more evident. NMR metabolomics and chemometrics revealed differences in urinary metabolites associated with CKD progression. The main physiological pathways affected were those involved in energy production and amino-acid metabolism, together with organic osmolytes. These data suggest that multiple administrations of FA induce a reproducible model of the induction of CKD. This model could help to evaluate new strategies for nephroprotection that could be applied in the clinic.
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BACKGROUND: Periampullary neoplasms account for over 30,000 cancer-related deaths per year in the United States. Pancreaticoduodenectomy (PD) is considered the surgical standard and is the only curative treatment option for these pathologies. OBJECTIVE: The objective of this study was to report the prognostic factors in survival and surgical complications in PD. MATERIALS AND METHODS: A total of 178 cases are reported, several variables were reviewed and the same surgical technique was used by the same surgeon. RESULTS: A total of 151 PD were reviewed. The most common initial symptoms were jaundice, 111 (73%), abdominal pain, 20 (13%), and oral intolerance, 10 (6%). Poor prognostic factors for survival were the presence of a previous pathology, days of hospitalization, positive margins, and weight loss. DISCUSSION: With the experience gained, a decrease in surgical time, intraoperative bleeding, and transfusions performed was achieved. Our complication rate remained at 20%, lower than that reported in literature. CONCLUSION: PD is the only option of cure for patients with pancreatic and periampullary tumors. This procedure has been linked to high morbidity and mortality even in high-volume centers. A pancreatic fistula is the most feared complication; therefore, multiple pancreatojejunostomy techniques have been described in literature. It is important to continue reporting these cases to reach a consensus on this technique.
ANTECEDENTES: Las neoplasias periampulares suponen más de 30.000 muertes relacionadas con el cáncer por año en los EE.UU. La pancreaticoduodenectomía (PD) se considera el estándar quirúrgico y es la única opción de tratamiento curativo para esta enfermedad. OBJETIVO: Reportar los factores de pronóstico en la supervivencia y las complicaciones quirúrgicas de la PD. . MÉTODO: Se reportaron 178 casos; se revisaron varias variables y se utilizó la misma técnica quirúrgica por el mismo cirujano. RESULTADOS: Se revisaron 151 DP. Los síntomas iniciales más comunes fueron ictericia (111; 73%), dolor abdominal (20; 13%) e intolerancia oral (10; 6%). Los factores de pronóstico para la supervivencia fueron la presencia de patología previa, los días de hospitalización, los márgenes positivos y la pérdida de peso. DISCUSIÓN: Con la experiencia adquirida, se logró una disminución del tiempo quirúrgico, del sangrado intraoperatorio y de las transfusiones realizadas. Nuestra tasa de complicaciones se mantuvo en un 20%, inferior a la reportada en la literatura. CONCLUSIÓN: La PD es la única opción de curación para los pacientes con tumores pancreáticos y periampulares. Este procedimiento se ha relacionado con una alta morbilidad y mortalidad incluso en centros de alto volumen. La fístula pancreática es la complicación más temida, por lo que se han descrito numerosas técnicas de pancreatoyeyunostomía. Es importante seguir informando de estos casos para llegar a un consenso sobre esta técnica.
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Neoplasias del Conducto Colédoco/cirugía , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/mortalidad , Complicaciones Posoperatorias/mortalidad , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias Duodenales/mortalidad , Neoplasias Duodenales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Pronóstico , Estudios Retrospectivos , Factores de TiempoRESUMEN
Osteoarthritis (OA) is a degenerative joint disease that affects the soft tissues and bones of involved articulations as a result of deregulation between synthesis and extracellular matrix degradation in articular cartilage. The present study evaluated the effect of intra-articular injection of human amniotic membrane (AM) as a treatment in an OA animal model in the knee. Chemical OA was developed in the knees of New Zealand rabbits. Once OA was established, the right knees only were treated with an intra-articular injection of human AM, with the left knees considered as a negative control group. The evaluation was performed at 3 and 6 weeks post-treatment. At 3 weeks post-injection, the cartilage exhibited fibrillation, erosion, cracks and cell clusters in the negative control group, but not in the treated group (P=0.028). At 6 weeks post-injection, the left knees exhibited hypertrophy, cracks, cell clusters, decreased matrix staining and structure loss. However, the right knees exhibited cell clusters without evidence of disruption in cartilage integrity (P=0.015). These results suggested that the intra-articular injection of human AM delays histological changes of cartilage in OA.
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BACKGROUND: Mycetoma is a chronic, localized infection caused by fungi and bacteria. It usually affects the skin, subcutaneous tissue, and bone of exposed areas with deformity of the affected limb, ulcers, and fistula; however, pain is not severe, therefore the patient comes late to hospital for care. OBJECTIVE: To establish the diagnosis of mycetoma in the foot by imaging and identify the principal radiological signs. MATERIALS AND METHODS: Six patients with foot mycetoma were evaluated with plain x-ray, ultrasound, and magnetic resonance (MR) after confirming the diagnosis by histopathology and culture. RESULTS: All patients presented the MR "dot-in-circle" sign; four presented "punched out" bone lesions on plain x-ray. The six patients had fistulas, ulceration, a seropurulent exudate, edema, and a foot deformity. Four patients had N. brasiliensis infection with positive anti-Nocardia IgG antibodies, and only half presented bone lesions. CONCLUSION: Characteristic findings were foot deformity, edema, bone lesions, ulcers, fistulas and the presence of the "dot-in-circle" sign. We recommend a comprehensive study of patients with plain x-ray and MR.
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Enfermedades del Pie/diagnóstico por imagen , Micetoma/diagnóstico por imagen , Adolescente , Adulto , Anciano , Femenino , Enfermedades del Pie/diagnóstico , Enfermedades del Pie/microbiología , Humanos , Masculino , Persona de Mediana Edad , Micetoma/diagnóstico , Micetoma/microbiologíaRESUMEN
ANTECEDENTES: El preacondicionamiento isquémico remoto (PIR) en trasplante hepático ha sido sugerido en el ámbito experimental como estrategia para disminuir la lesión por isquemia- reperfusión. OBJETIVO: Evaluar el efecto del PIR sobre el injerto hepático en donante cadáver y el impacto de diversos mediadores inflamatorios en este proceso. MÉTODO: Se incluyeron 10 receptores de trasplante hepático, 5 controles y 5 con PIR, el cual fue realizado en los donantes cadavéricos mediante la aplicación de un torniquete neumático en ambos muslos por 10 minutos seguido de 10 minutos de reperfusión. Se determinaron interleucina (IL)-1, IL-6, factor de necrosis tumoral alfa (FNT-α), factor de crecimiento endotelial vascular (FCEV) y molécula de adhesión intracelular (ICAM)-1, parámetros hematológicos y bioquímicos en diversas fases del trasplante hepático. RESULTADOS: Se observó un aumento significativo de la aspartato aminotransferasa (AST), la alanino aminotransferasa (ALT) y la fosfatasa alcalina en las fases tempranas tras el trasplante hepático, y a las 72 horas los sujetos con PIR mostraron mejor respuesta, con recuperación de plaquetas, que persistió hasta los 3 meses en este grupo. La IL-6 participa en las fases tempranas de la lesión por isquemia- reperfusión, contrario al FNT-α, que se incrementa hasta el día 7, mientras que la ICAM-1 aumentó en todas las fases. CONCLUSIONES: En este estudio piloto, el PIR disminuyó el daño por lesión por isquemia- reperfusión, aunque el mayor efecto se observó después de 72 horas. BACKGROUND: Remote ischemic preconditioning (RIP) in liver transplantation has been suggested experimentally as a strategy to reduce ischemia-reperfusion injury. OBJECTIVE: Evaluate the effect of RIP on liver graft in cadaveric donors and the impact of various inflammatory mediators in this process. METHOD: Ten liver transplantation recipients, 5 controls and 5 PIR, were made in the cadaver donors by applying a pneumatic tourniquet in the upper third of both thighs for a period of 10 minutes followed by 10 minutes reperfusion. The determination of interleukine (IL)-1, IL-6, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), intracellular adhesion molecule (ICAM)-1 was performed as well as hematological and biochemical parameters at various stages of liver transplantation. RESULTS: Significant increase of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase in the early stages of post-liver transplantation were observed, after 72 hours subjects who received liver transplantation subjected to RIP they showed a better response, which was also evident in platelet recovery, which persisted until phase 3 months in this group. IL-6 appears to participate in the early stages of the ischemia-reperfusion injury, contrary to TNF-α that increases until day 7 while ICAM-1 was increased in all phases. CONCLUSIONS: In this pilot study the PIR decreased the damage by ischemia-reperfusion injury, although the greatest effect was observed after 72 hours.
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Precondicionamiento Isquémico/métodos , Trasplante de Hígado , Hígado/irrigación sanguínea , Supervivencia Tisular , Adulto , Citocinas/sangre , Femenino , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Masculino , Persona de Mediana Edad , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
BACKGROUND: Thyroxine (T4) has been positively associated with tumor cell proliferation, while the effect of triiodothyronine (T3) on cell proliferation has not been well-established because it differs according to the type of cell line used. In Mexico, it has been reported that 14.5% of adult women have some type of thyroid dysfunction and abnormalities in thyroid function tests have been observed in a variety of non-thyroidal illnesses, including breast cancer (BC). These abnormalities might change with body mass index (BMI) because thyroid hormones are involved in the regulation of various metabolic pathways and probably by menopausal status because obesity has been negatively associated with BC in premenopausal women and has been positively associated with BC in postmenopausal women. METHODS: To assess the association between serum thyroid hormone concentration (T4 and T3) and BC and the influence of obesity as an effect modifier of this relationship in premenopausal and postmenopausal women, we measured serum thyroid hormone and thyroid antibody levels in 682 patients with incident breast cancer (cases) and 731 controls, who participated in a population-based case-control study performed from 2004 to 2007 in three states of Mexico. We tested the association of total T4 (TT4) and total T3 (TT3) stratifying by menopausal status and body mass index (BMI), and adjusted for other health and demographic risk factors using logistic regressions models. RESULTS: Higher serum total T4 (TT4) concentrations were associated with BC in both premenopausal (odds ratio (OR) per standard deviation = 5.98, 95% CI 3.01-11.90) and postmenopausal women (OR per standard deviation = 2.81, 95% CI 2.17-3.65). In premenopausal women, the effect of TT4 decreased as BMI increased while the opposite was observed in postmenopausal women. The significance of the effect modification was marginal (p = 0.059) in postmenopausal women and was not significant in premenopausal women (p = 0.22). Lower TT3 concentrations were associated with BC in both premenopausal and postmenopausal women and no effect modification was observed. CONCLUSIONS: There is a strong association between BC and serum concentrations of TT3 and TT4; this needs to be further investigated to understand why it happens and how important it is to consider these alterations in treatment.
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Índice de Masa Corporal , Neoplasias de la Mama/epidemiología , Obesidad/epidemiología , Tiroxina/sangre , Triyodotironina/sangre , Adulto , Neoplasias de la Mama/sangre , Estudios de Casos y Controles , Femenino , Humanos , Incidencia , México/epidemiología , Persona de Mediana Edad , Obesidad/sangre , Posmenopausia/sangre , Premenopausia/sangreRESUMEN
INTRODUCTION: Kidney ischemia-reperfusion (I/R) injury is the main cause of delayed graft function in solid organ transplantation. Sonchus oleraceus is a plant with well-known antioxidant and anti-inflammatory activities; however, its effects on renal I/R are unknown. OBJECTIVE: To evaluate whether S. oleraceus extract (S.O.e.) has nephroprotective activity in an I/R model in Wistar rats. MATERIALS AND METHODS: Animal groups (n = 6): sham, I/R (45 min/15 h), S.O.e (300 mg/kg p.o.), and S.O.e + I/R (300 mg/kg, p.o.; 45 min/15 h). Renal function, proinflammatory cytokines, alanine aminotransferase, markers of oxidative stress, and histology were evaluated. RESULTS: None of the mediators evaluated differed significantly between the S.O.e and sham groups. Levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and proinflammatory cytokines were higher, and superoxide dismutase (SOD) was lower in the I/R group than in the sham group. Histology showed tubular epithelial necrosis in the medulla and cortex in the I/R group. In the S.O.e + I/R group, S.O.e pretreatment attenuated the I/R-induced increases in BUN, creatinine, MDA, and proinflammatory cytokines induced, SOD was maintained, and histology showed discontinuous necrosis in the medulla but no necrosis in the cortex. CONCLUSIONS: S.O.e was neither hepatotoxic nor nephrotoxic. S.O.e. pretreatment showed a nephroprotective effect against I/R.
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Riñón/irrigación sanguínea , Extractos Vegetales/farmacología , Insuficiencia Renal/prevención & control , Daño por Reperfusión/tratamiento farmacológico , Sonchus/química , Animales , Riñón/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Insuficiencia Renal/tratamiento farmacológico , Insuficiencia Renal/etiología , Daño por Reperfusión/patologíaRESUMEN
Con una prevalencia global reportada de entre 11-13%, la enfermedad renal crónica (ERC) ha sido reconocida como un gran desafío para los sistemas de salud por sus implicaciones económicas y sociales. Al tratarse de una enfermedad crónica e irreversible, el tratamiento está dirigido a disminuir su progresión. La cuantificación de creatinina sérica es el método de elección para su diagnóstico y clasificación; sin embargo, es conocido que esta prueba tiene una sensibilidad clínica limitada, lo que ha conducido a la búsqueda de nuevos marcadores que permitan un diagnóstico y monitoreo oportuno. Desde esta perspectiva, el empleo de la metabolómica y de modelos animales ha permitido la identificación y estudio de nuevos metabolitos, candidatos a ser utilizados como futuros biomarcadores en la práctica clínica. La presente revisión tuvo como objetivo hacer una análisis de los perfiles metabolómicos reportados para la ERC, tanto en modelos experimentales como en estudios realizados en seres humanos. De acuerdo a los datos obtenidos, los metabolitos implicados en las rutas metabólicas de aminas cuaternarias y aminoácidos como el TMNO, el indoxilsulfato y derivados de la dimetilarginina representan una alternativa prometedora para la identificación, clasificación y pronóstico de la ERC.
Chronic kidney disease (CKD) high global prevalence, estimated between 11 to 13%, has been recognized as a mayor health challenge for healthcare systems due to its relevant economic and social implications. Main medical intervention strategies are directed to delay the progression of CKD and prevent outcomes. Serum creatinine concentration has been used to classify CKD and define its progression stage; however, it is well known the low sensitivity shown by this test. This fact has conducted to the search for new markers in order to improve the disease diagnosis, monitoring and treatment. In this context, metabolomics science and animal models have allowed identification of new metabolites that can be used as future biomarkers into clinical practice. This review aims to summarize the metabolomics profiles reported in different experimental models and clinical research on CKD. According with the data obtained, metabolites related with quaternary amines and aminoacid metabolic pathways like TMNO, indoxyl sulfate and dimethylarginine, suggest a promising alternative for identification, classification and prognosis of CKD.
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BACKGROUND: Through experience it has been accepted that bile in normal conditions remains sterile. Bactibilia is a common finding in individuals at high risk or with complicated cholecystolithiasis, however few data prevails about the prevalence of bactibilia in patients operated on for uncomplicated laparoscopic cholecystectomy. There is s common usage of preoperative and postoperative antibiotics in the different patients without the existence of any actual bacteriologic and epidemiologic evidence. MATERIAL AND METHODS: 183 patients with diagnosis of cholecystolithiasis postoperated of laparoscopic cholecystectomy had their bile sent to bacteriology. RESULTS: Bactibilia was identified in 31.95% of the cultures of mild cholecystitis and in 35.71% for moderate (p<.0001). A total of 125 negative cultures were obtained (68.3) and 58 positive (31.69%) with a prevalence of enterobacteria group (43.10%) and Enterococcus (27.58). CONCLUSIONS: Comparing the groups according to severity there is a significant difference with regard to the presence of bactibilia, in addition to the bacterial groups cultivated. Fluoroquinolones and metronidazole is an option for the treatment of patients with the suspicion of bactibilia. The use of antibiotics is not justified in patients at low risk.