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OBJECTIVE: To describe our experience with treprostinil, evaluate correlations with cardiac function, and assess for adverse effects in neonates with congenital diaphragmatic hernia-related pulmonary hypertension (CDH-PH). STUDY DESIGN: A retrospective review of a single-center prospective registry at a quaternary care children's hospital. Patients included in the study had CDH-PH treated with treprostinil between April 2013 and September 2021. Assessed outcomes were brain-type natriuretic peptide levels and quantitative echocardiographic parameters collected at baseline, 1 week, 2 weeks, and 1 month after treprostinil initiation. Right ventricular (RV) function was assessed by tricuspid annular plane systolic excursion Z-score and speckle tracking echocardiography (global longitudinal and free wall strain). Septal position and left ventricular (LV) compression were assessed by eccentricity index and M-mode Z-scores. RESULTS: Fifty-one patients were included, with an average expected/observed lung-to-head ratio of 28.4 ± 9.0%. Most patients required extra-corporeal membrane oxygenation (n = 45, 88%). Survival to hospital discharge was 31/49 (63%). Treprostinil was initiated at a median age of 19 days with a median effective dose of 34 ng/kg/minute. Median baseline brain-type natriuretic peptide level decreased from 416.9 pg/mL to 120.5 pg/mL after 1 month. Treprostinil was associated with improved tricuspid annular plane systolic excursion Z-score, RV global longitudinal strain, RV free wall strain, LV eccentricity index, and LV diastolic and systolic dimensions, reflecting less compression by the RV, regardless of ultimate patient survival. No serious adverse effects were recorded. CONCLUSIONS: In neonates with CDH-PH, treprostinil administration is well tolerated and is associated with improved RV size and function.

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BACKGROUND/HYPOTHESIS: The Latarjet procedure changes the anatomy of the shoulder, moving the coracoid process distally through an incision in the subscapularis muscle. Some authors have studied the effect of this surgery on shoulder rotator strength. Our hypothesis is that the Latarjet procedure decreases elbow supination and flexion strength. METHODS: A retrospective case series, evaluating patients submitted to the Latarjet procedure between May 2013 and June 2017. Movements of the elbow (supination, pronation, flexion and extension) and shoulder (internal and external rotation) were evaluated bilaterally using a Biodex System 3 isokinetic dynamometer (Biodex Medical Systems, New York) in concentric/concentric mode. RESULTS: We evaluated 20 patients with an average follow-up of 36 months. In the elbow, we observed a 9.1% decrease in supination strength at a speed of 60°/s (p=0.044), without statistical difference at 120°/s (p=0.570). In the shoulder, there was a 13.5% decrease in external rotation strength at 60°/s and 4.5% at 180°/s (p=0.009 and p=0.040, respectively). The other movements did not demonstrate any statistically significant differences. CONCLUSION: After the Latarjet procedure, the supination strength at 60°/s was decreased, as was the external rotation strength of the shoulder at 60°/s and 180°/s. We did not observe any reduction in strength for shoulder flexion or internal shoulder rotation. LEVEL OF EVIDENCE: IV, case series.

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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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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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BACKGROUND: In low- and middle-income countries emergency surgery represents a higher proportion of the total number of surgeries and is associated with greater morbidity/mortality. Study aims were to determine if emergency department length of stay (ED-LOS) was associated with adverse perioperative outcomes and if such association varied across patient's risk categories. METHODS: A retrospective cohort study was conducted of adult patients who underwent orthopedic or abdominal emergency surgery at two Colombian University hospitals. The population comprised a mix of a representative sample of eligible cases, with unselected patients (2/3), enriched with a high-risk subset (1/3). ED-LOS was defined as the interval between emergency department arrival and surgery start time. Our primary outcome was an adverse perioperative outcome during hospitalization, which was a composite of in-hospital mortality or severe complications such as major cardiovascular adverse events, infection, renal failure and bleeding. RESULTS: Among 1487 patients analyzed, there were 519 adverse perioperative outcomes including 150 deaths. In the unselected sample (n = 998) 17.9% of patients presented an adverse perioperative outcome with a mortality of 4.9%. The median ED-LOS was 24.6 (IQR 12.5-53.2) hours. ED-LOS was associated with age, comorbidities and known risk factors for 30-day mortality. Patients developing an adverse perioperative outcome started surgery 27.1 h later than their counterparts. Prolonged ED-LOS increased the risk of an adverse perioperative outcome in patients without risk factors (covariate-adjusted OR = 2.52), while having 1-2 or 3+ risk factors was negatively associated (OR = 0.87 and 0.72, respectively, p < 0.001 for the interaction). CONCLUSION: Prolonged ED-LOS is associated with increased adverse perioperative outcome for patients without risk factors for mortality, but seems protective and medically justified for more complex cases.

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The distribution of orthopoxviruses (OPXVs) across the North American continent is suggested to be widespread in a wide range of mammalian hosts on the basis of serosurveillance studies. To address the question of whether carnivores in northwestern Mexico are exposed to naturally circulating OPXVs, wild carnivores were collected by live trapping within four different habitat types during fall of 2013 and spring of 2014 within the Janos Biosphere Reserve in northwestern Chihuahua, Mexico. A total of 51 blood samples was collected for testing. Anti-OPXV immunoglobulin G enzymelinked immunosorbent assay, western blot, and rapid fluorescent focus inhibition test (RFFIT) assays were conducted. About 47% (24/51) of the carnivores tested were seropositive for anti-OPXV binding antibodies and had presence of immunodominant bands indicative of OPXV infection. All samples tested were negative for rabies virus neutralizing antibodies by RFFIT, suggesting that the OPXV antibodies were due to circulating OPXV, and not from exposure to oral rabies vaccine (vacciniavectored rabies glycoprotein vaccine) bait distributed along the US-Mexico border. Our results indicated that there may be one or more endemic OPXV circulating within six species of carnivores in northwestern Mexico.

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[This corrects the article DOI: 10.1155/2010/834060.].

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Resumen Introducción: Un estilo de vida saludable es determinante para la salud cardiovascular. Existe controversia en los efectos vasculares benéficos del ejercicio físico. Objetivo: Evaluar el comportamiento de los parámetros de rigidez vascular en una población sana que practica ejercicio aeróbico rutinario en comparación con una población sana sedentaria. Métodos: Estudio de 32 sujetos sanos, pareados por edad y sexo: 12 hombres y 20 mujeres (46,3 ± 9,7 años), en el cual se evaluaron y compararon los parámetros de rigidez arterial (presión sistólica y diastólica braquial, índices de aumentación braquial y central, velocidad de onda de pulso, presión sistólica y diastólica central, y presión de pulso braquial y central). Las mediciones se hicieron con el método no invasivo-oscilométrico, Arteriograph® (TensioMed Budapest Hungría, Ltd.). Resultados: Se compararon los parámetros de rigidez arterial entre los dos grupos (16 sujetos activos vs. 16 sedentarios), y se encontraron diferencias significativas en los siguientes: frecuencia cardiaca de 53,25 ± 8,0 lpm vs. 59,75± 8,6 lpm (p = 0,034), presión arterial diastólica braquial de 70,0 (4,5) mm Hg vs. 77,5 (8,3) mm Hg (p = 0,043), presión arterial diastólica central de 70,0 (4,5) mm Hg vs. 77,5 (8,1) mm Hg (p = 0,043) y velocidad de onda de pulso de 6,70 (1,1) m/s vs. 7,75 (1,1) m/s (p = 0,001). Conclusiones: La actividad física aeróbica rutinaria tiene un efecto benéfico sobre la rigidez vascular en una población sana, a expensas de una disminución significativa de la velocidad de onda de pulso, la frecuencia cardiaca y la presión arterial diastólica (braquial y central). Estos hallazgos ayudan a explicar los beneficios del ejercicio aeróbico sobre el sistema cardiovascular.

Abstract Introduction: A healthy lifestyle is key for cardiovascular health. There is controversy about beneficial vascular effects of physical exercise. Motivation: To assess the behaviour of vascular stiffness parametres in a healthy population group that practices routine aerobic exercise in comparison with another group of healthy population with a sedentary lifestyle. Methods: Study of 32 healthy individuals, paired according to age and gender: 12 men and 20 women (46.3±9.7 years old); the study assessed and compared arterial stiffness parametres (brachial systolic and diastolic blood pressure, brachial and central augmentation index, pulse wave velocity, central systolic and diastolic blood pressure and brachial and central pulse pressure).Measurements were conducted using the noninvasive oscillometric method Arteriograph® (TensioMed Budapest Hungary, Ltd.). Results: Arterial stiffness parametres were compared between both groups (16 active individuals vs. 16 sedentary ones), and the following significant differences were found: heart rate 53.25 ± 8.0 bpm vs. 59.75 ± 8.6 bpm (p = 0.034), brachial diastolic blood pressure of 70.0 (4.5) mmHg vs. 77.5 (8.3) mmHg (p = 0.043), central diastolic blood pressure of 70.0 (4.5) mmHg vs. 77.5 (8.1) mmHg (p = 0.043) and pulse wave velocity of 6.70 (1.1) m/s vs. 7.75 (1.1) m/s (p = 0.001). Conclusions: Routine aerobic exercise has a beneficial effect on vascular stiffness in a healthy population group, at the expense of a significant decrease in pulse wave velocity, heart rate and diastolic blood pressure (both brachial and central). These findings help explain the benefits of aerobic exercise on the cardiovascular system.

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