Female sex does not influence 30-day stroke and mortality rates after carotid endarterectomy.

BACKGROUND: Sex-based differences in outcomes for the treatment of carotid arterial disease remains a controversial topic. The main objective of this study was to determine if gender differences influence 30-day stroke and mortality rates after carotid endarterectomy (CEA) in a large series of patients. METHODS: This is a retrospective study of all patients undergoing endarterectomy performed by a single surgeon between January 1, 1993 and December 15, 2010. The analysis included data from 1,046 CEAs (683 men and 363 women). RESULTS: There were no differences found in 30-day stroke, death, or combined stroke and death rates between women and men. The 30-day stroke rate was 1.6% for women and 1.8% for men (P = 0.98), with no significant differences between asymptomatic patients (1.7% for women vs. 1.2% for men; P = 0.70) or symptomatic patients (1.6% for women vs. 2.1% for men; P = 0.74). The 30-day mortality rate was 0.8% for women and 0.9% for men (P = 0.85) with no significant differences between asymptomatic patients (0.8% for women vs. 1.2% for men; P = 0.77) and symptomatic patients (0.8% for women vs. 0.7% for men; P = 0.84). There was a similar low risk for the combined outcome of stroke and death (1.9% for women vs. 2.2% for men; P = 0.92), with no differences between asymptomatic patients (1.7% for women vs. 1.6% for men; P = 0.89) or symptomatic patients (2.1% for women vs. 2.5% for men; P = 0.84). CONCLUSIONS: Female sex does not influence 30-day stroke and mortality rates after CEA, regardless of preoperative symptom status.

CoVITEST: A Fast and Reliable Method to Monitor Anti-SARS-CoV-2 Specific T Cells From Whole Blood.

Cellular and humoral immune responses are essential for COVID-19 recovery and protection against SARS-CoV-2 reinfection. To date, the evaluation of SARS-CoV-2 immune protection has mainly focused on antibody detection, generally disregarding the cellular response, or placing it in a secondary position. This phenomenon may be explained by the complex nature of the assays needed to analyze cellular immunity compared with the technically simple and automated detection of antibodies. Nevertheless, a large body of evidence supports the relevance of the T cell's role in protection against SARS-CoV-2, especially in vulnerable individuals with a weakened immune system (such as the population over 65 and patients with immunodeficiencies). Here we propose to use CoVITEST (Covid19 anti-Viral Immunity based on T cells for Evaluation in a Simple Test), a fast, affordable and accessible in-house assay that, together with a diagnostic matrix, allows us to determine those patients who might be protected with SARS-CoV-2-reactive T cells. The method was established using healthy SARS-CoV-2-naïve donors pre- and post-vaccination (n=30), and further validated with convalescent COVID-19 donors (n=51) in a side-by-side comparison with the gold standard IFN-γ ELISpot. We demonstrated that our CoVITEST presented reliable and comparable results to those obtained with the ELISpot technique in a considerably shorter time (less than 8 hours). In conclusion, we present a simple but reliable assay to determine cellular immunity against SARS-CoV-2 that can be used routinely during this pandemic to monitor the immune status in vulnerable patients and thereby adjust their therapeutic approaches. This method might indeed help to optimize and improve decision-making protocols for re-vaccination against SARS-CoV-2, at least for some population subsets.

Prevalencia de aspergilosis broncopulmonar alérgica en niños con fibrosis quística / Prevalence of bronchopulmonary aspergillosis in children with cystic fibrosis

La aspergilosis broncopulmonar alérgica (ABPA) es una reacción de hipersensibilidad secundaria al Aspergillus fumigatus (Af) que complica la evolución en fibrosis quística (FQ). Existen pocos estudios pediátricos de su prevalencia publicados en el mundo y en Chile se desconoce. El objetivo de este trabajo fue estimar la prevalencia de ABPA en niños con FQ en un hospital de referencia, explorar factores de riesgo y describir los criterios diagnósticos, tratamiento y evolución. Se incluyeron retrospectivamente los niños con FQ atendidos en un hospital terciario en Santiago de Chile (Hospital Roberto del Río) entre los años 2011 a 2019, se identificaron aquellos con diagnóstico de ABPA. Se registraron criterios diagnósticos según la Cystic Fibrosis Foundation, presencia de factores de riesgo, tratamientos recibidos y efectos adversos. De 65 pacientes con FQ atendidos en este período, la prevalencia de ABPA fue del 12%. El promedio de edad al diagnóstico fue ± 11 años (5-17 años), predominando la edad adolescente y el género masculino. El 50% cumplieron con los criterios clásicos, el 87,5% usaron antibióticos y el 62,5% corticoides inhalados. La respuesta favorable al tratamiento inicial con corticoides y antifúngico vía oral fue 62,5%, con una exacerbación al momento del estudio. El 25% se comportaron como refractario y el 12,5% respondieron a tratamiento con pulsos de metilprednisolona. El 37,5% presentaron eventos adversos relacionados a corticoides. La prevalencia de ABPA observada es comparable a las series publicadas. Se necesitan trabajos prospectivos para conocer la prevalencia nacional y su tendencia a lo largo de los años, identificando factores de riesgo.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity response to Aspergillus fumigatus (Af) and worsens outcome in children with cystic fibrosis (CF). Its prevalence varies in the literature, but we do not know it in Chile. The aim of the study was to know the prevalence of ABPA in children with CF and to describe risk factors, diagnostic criteria, treatment and outcome. We included all patients with CF seen in a tertiary hospital in Santiago, Chile (Hospital Roberto del Río), between 2011 and 2019; ABPA cases (CF Foundation diagnostic criteria) were identified for the estimation of the prevalence. Risk factors, diagnostic criteria and treatment were recorded, as proposed by the Cystic Fibrosis Foundation. A total of 65 patients with CF were identified in the study period, with a prevalence of 12% (8 cases). Mean age at diagnosis ± 11 years (5-17), more frequent in adolescence and male. CF Foundation criteria diagnostic were identified in 50% of cases, with high frequency of antibiotic use (87,5%) and inhaled steroids (62,5%). Positive oral steroids and antifungal treatment response was 62,5%. Refractary response was 25% and 12,5% needed intravenous metilprednisolone pulses. A 37,5% of cases presented adverse effects to steroids. Prevalence of ABPA is comparable to literature. A prospective study is needed to identified national prevalence and trends, identifying risks factors.

Estrogen and progesterone up-regulate glucose transporter expression in ZR-75-1 human breast cancer cells.

Breast cancer incidence increases in women receiving combined estrogen and progesterone therapy. Breast tumors show increased expression of the glucose transporter GLUT1. We determined the effect of these hormones on GLUT1-4 expression and deoxyglucose transport in ZR-75-1 breast cancer cells. Immunoblotting, immunocytochemistry, flow cytometry, and RT-PCR showed that GLUT1 expression is up-regulated by progesterone and, to a greater degree, combined therapy. GLUT2 expression is unaffected by hormonal treatment. GLUT3 protein and RNA is up-regulated by progesterone and combined therapy, and GLUT4 protein expression is up-regulated by all hormonal treatments. Deoxyglucose transport studies revealed the presence of three transport components with characteristics corresponding to GLUT1/4, GLUT2, and GLUT3. 17beta-Estradiol produced a slight increase in transport at the Michaelis constant (Km) corresponding to GLUT3. Progesterone produced a small increase in transport at the Km corresponding to GLUT1/4, and combined 17beta-estradiol and progesterone produced a small increase in transport at the Km corresponding to GLUT3 and a large increase in transport at the Km corresponding to GLUT1/4. This indicates that 17beta-estradiol and progesterone differentially regulate GLUT1-4 expression and that these changes correlate to changes in glucose uptake. We postulate that combined hormone replacement therapy provides a survival advantage to developing ZR-75 breast cancer cells.

Differential regulation of glucose transporter expression by estrogen and progesterone in Ishikawa endometrial cancer cells.

Estrogen replacement therapy and other unopposed estrogen treatments increase the incidence of endometrial abnormalities, including cancer. However, this effect is counteracted by the co-administration of progesterone. In the endometrium, glucose transporter (GLUT) expression and glucose transport are known to fluctuate throughout the menstrual cycle. Here, we determined the effect of estrogen and progesterone on the expression of GLUT1-4 and on the transport of deoxyglucose in Ishikawa endometrial cancer cells. Cells were incubated with estrogen, progesterone or combined estrogen and progesterone for 24 h and the effect on the expression of GLUT1-4 and on deoxyglucose transport was determined. We show that GLUT1 expression is upregulated by estrogen and progesterone individually, but that combined estrogen and progesterone treatment reverses this increase. Hormonal treatments do not affect GLUT2, GLUT3 or GLUT4 expression. Transport studies demonstrate that estrogen increases deoxyglucose transport at Michaelis-Menten constants (Kms) corresponding to GLUT1/4, an effect which disappears when progesterone is added concomitantly. These data demonstrate that different hormonal treatments differentially regulate GLUT expression and glucose transport in this endometrial cancer cell line. This regulation mirrors the role played by estrogen and progesterone on the incidence of cancer in this tissue and suggests that GLUT1 may be utilized by endometrial cancer cells to fuel their demand for increased energy requirement.

Mechanistic insights and functional determinants of the transport cycle of the ascorbic acid transporter SVCT2. Activation by sodium and absolute dependence on bivalent cations.

We characterized the human Na(+)-ascorbic acid transporter SVCT2 and developed a basic model for the transport cycle that challenges the current view that it functions as a Na(+)-dependent transporter. The properties of SVCT2 are modulated by Ca(2+)/Mg(2+) and a reciprocal functional interaction between Na(+) and ascorbic acid that defines the substrate binding order and the transport stoichiometry. Na(+) increased the ascorbic acid transport rate in a cooperative manner, decreasing the transport K(m) without affecting the V(max), thus converting a low affinity form of the transporter into a high affinity transporter. Inversely, ascorbic acid affected in a bimodal and concentration-dependent manner the Na(+) cooperativity, with absence of cooperativity at low and high ascorbic acid concentrations. Our data are consistent with a transport cycle characterized by a Na(+):ascorbic acid stoichiometry of 2:1 and a substrate binding order of the type Na(+):ascorbic acid:Na(+). However, SVCT2 is not electrogenic. SVCT2 showed an absolute requirement for Ca(2+)/Mg(2+) for function, with both cations switching the transporter from an inactive into an active conformation by increasing the transport V(max) without affecting the transport K(m) or the Na(+) cooperativity. Our data indicate that SVCT2 may switch between a number of states with characteristic properties, including an inactive conformation in the absence of Ca(2+)/Mg(2+). At least three active states can be envisioned, including a low affinity conformation at Na(+) concentrations below 20 mM and two high affinity conformations at elevated Na(+) concentrations whose Na(+) cooperativity is modulated by ascorbic acid. Thus, SVCT2 is a Ca(2+)/Mg(2+)-dependent transporter.

Vitamin C is an essential antioxidant that enhances survival of oxidatively stressed human vascular endothelial cells in the presence of a vast molar excess of glutathione.

Cellular glutathione levels may exceed vitamin C levels by 10-fold, generating the question about the real antioxidant role that low intracellular concentrations of vitamin C can play in the presence of a vast molar excess of glutathione. We characterized the metabolism of vitamin C and its relationship with glutathione in primary cultures of human endothelial cells oxidatively challenged by treatment with hydrogen peroxide or with activated cells undergoing the respiratory burst, and analyzed the manner in which vitamin C interacts with glutathione to increase the antioxidant capacity of cells. Our data indicate that: (i) endothelial cells express transporters for reduced and oxidized vitamin C and accumulate ascorbic acid with participation of glutathione-dependent dehydroascorbic acid reductases, (ii) although increased intracellular levels of vitamin C or glutathione caused augmented resistance to oxidative stress, 10-times more glutathione than vitamin C was required, (iii) full antioxidant protection required the simultaneous presence of intracellular and extracellular vitamin C at concentrations normally found in vivo, and (iv) intracellular vitamin C cooperated in enhancing glutathione recovery after oxidative challenge thus providing cells with enhanced survival potential, while extracellular vitamin C was recycled through a mechanism involving the simultaneous neutralization of oxidant species. Therefore, in endothelial cells under oxidative challenge, vitamin C functions as an essential cellular antioxidant even in the presence of a vast molar excess of glutathione.

Tomografía axial computada y resonancia nuclear magnética en pacientes pediátricos: avances y nuevos desafíos / Computed axial tomography and magnetic resonance imaging in pediatric patients: advances and new challenges

The introduction of computed axial tomography (CAT) and magnetic resonance imaging (NMR) in the study of pediatric patients has led to a growing need for sedation and anaesthesia in imaging units. Scientific societies for Pediatrics, Radiology, and Anaesthesia have jointly prepared guides and recommendations establishing standards which regulate procedures, in attempts to guarantee efficiency, security, and economy. Many centers have compiled experiences and developed protocols to report on techniques and behaviors which have permitted a better understanding of patient needs and reduction of numbers of unsuccessful procedures. At present there exist a variety of techniques for sedation and anaesthesia which conform to these standards. Ultimately, present evidence suggest that assistence rendered by anaesthesiologist physician. Training of personnel reduces variability in success of the procedures as well as their costs, and the best decision which guarantees efficiency and security is that which is made on a individual basis considering the characteristics of the patient, availability of trained personnel, equipment, and experience of the health professional in charge.

La introducción de la tomografía axial computada y la resonancia nuclear magnética en el estudio del paciente pediátrico se tradujo en una creciente necesidad se sedación y anestesia en las unidades de imagenología. Las sociedades científicas, de Pediatría, Radiología y Anestesiología, en conjunto han elaborado guías y recomendaciones donde establecen los estándares que norman los procedimientos buscando garantizar eficacia, seguridad y economía. Muchos centros han recopilado experiencias y desarrollado protocolos para uniformar técnicas y conductas, lo que ha permitido un mayor entendimiento de las necesidades de los pacientes y una disminución en el número de los procedimientos fallidos. Actualmente, existen variadas técnicas de sedación y anestesia que cumplen con dichos estándares. Por último, la evidencia actual señala que la asistencia otorgada por un anestesiólogo es más segura que la del médico no anestesiólogo; que el entrenamiento del personal reduce la variabilidad del procedimiento y los costos, y que la decisión que mejor garantiza la eficacia y seguridad es aquella que se hace en forma individualizada, considerando las características del paciente, la disponibilidad de personal entrenado y equipos y la experiencia del profesional a cargo.

Evaluación de la terapia de reemplazo hormonal en usuarias del programa climaterio a nivel de atención primaria, Antofagasta, 2002 / Evaluation of hormone replacement therapy in users of the climacteric program at the basic treatment level, Antofagasta, 2002

The benefits of hormone replacement therapy (HRT) have been widely demonstrated, and in theory, all climacteric women should receive it, except for those who demonstrate absolute contraindications. A study was made of 83 active users of HRT in the Climacteric Subprogram at a primary Treatment Clinic at Antofagasta. The average age of this group was 56 years, with an average age at menopause of 47 years and initiation of HRT treatment of 50 years. The range of time of therapy was from 3 to 5 years. Farlupost (37 percent) and Killios (24 percent) were the types of hormonal treatment most utilized. A rate of 92 percent of physiological menopause was observed, and predominant pretherapy symptoms included fluhing (42 percent), bone pain (18 percent), and headache (18 percent). With development of therapy, 72.3 percent reported being asymptomatic, and the remainig individuals had bone pain (35 percent), flushing (31 percent), headache (13 percent), sweating (13 percent), and insomnia (8 percent). A total of 94 percent would not elect to suspend the HRT for fear of reappearance of symptoms, with the only cause for abandoning the treatment being bleeding. During the study, 67.4 percent took supplementary calcium and 39 percent carried out physical exercise, primmarily walking. Improvement in family relations was cited by 43.4 percent, improved self esteem in 54.2 percent and sexual improvement in 37.3 percent.

Están ampliamente demostrados los beneficios de la terapia de reemplazo hormonal (TRH) y, en teoría, todas las mujeres climatéricas deberían recibirla, a menos que presenten contraindicaciones absolutas. Se estudió a 83 usuarias activas con terapia de reemplazo hormonal (TRH) del Subprograma Climaterio en un Consultorio de Atención Primaria de Antofagasta. El promedio de edad actual en este grupo de 56 años, con edad media de menopausia de 47 años e inicio de TRH de 50 años. El rango de tiempo de terapia fue de 3 a 5 años. Farlupost (37 percent) y Killios (24 por ciento) fueron los tipos de terapia hormonal más utilizados. Se constató un 92 por ciento de menopausia fisiológica y la sintomatología predominante preterapia fue bochornos (42 por ciento), dolor óseo (18 por ciento) y cefalea (18 por ciento). En la evolución con terapia el 72,3 por ciento refirió encontrarse asintomática, mientras que persistieron dolor óseo (35 por ciento), bochornos (31 por ciento), cefalea (13 por ciento), sudoración (13 por ciento) e insomnio (8 por ciento). Un 94 por ciento no suspendería la TRH temiendo la reaparición de síntomas y la única causal de abandono aludida fue el sangramiento. Al momento del estudio el 67,4 por ciento toma suplemento de calcio y un 39,7 por ciento realiza actividad física, principalmente caminata. Se asoció mejoría en el ámbito familiar en un 43,4 por ciento, autoestima en 54,2 por ciento y sexual en 37,3 por ciento.