Short-Term Effectiveness and Reduction in Insulin Requirements in Patients With Type 2 Diabetes Treated With IdegLira in a Real-World Setting.

Background: Type 2 diabetes mellitus (T2DM) is a chronic, highly prevalent disease with a significant impact on health. Appropriate treatment requires effective and timely escalation to achieve metabolic control. To evaluate the effectiveness and safety of IDegLira on adults with T2DM previously treated with oral antidiabetics and/or insulin in a real-life setting. Methods: An observational study in a real-world setting was conducted. Patients were selected from the outpatient clinic of two centers dedicated to specialized diabetes care. Main outcomes were HbA1c, body weight, insulin dose changes, hypoglycemia, and other adverse events. Results: 67 T2DM patients treated with IDegLira were monitored between 3 and 7 months. At the end of foll ow-up, the median change in HbA1c was -1.05% (CI95% -1.45, -0.65), and a decrease in insulin requirement was also observed (mean difference -10 TDD units (CI95% - 17 to -2.5). No treatment discontinuation was reported, hypoglycemia events were reported in 3 patients at the end of follow-up versus 8 patients at baseline. Conclusions: This real-life study shows the effectiveness in glycemic control of IDegLira use in T2DM patients who do not achieve goals with other therapies, with an adequate safety profile. The findings need to be confirmed with evaluation of therapeutic results in larger cohorts.

The effectiveness of a comprehensive diabetes program for glycemic control and adherence, and the selection of candidates for sensor-augmented insulin pump therapy.

OBJECTIVE: This study aimed to estimate the effectiveness of a comprehensive diabetes program (CDP) in terms of glycemic control, adherence, and the selection of candidates for sensor-augmented insulin pump therapy (SAP). METHODS: We compared diabetes control before and 6 months after CDP. The program was based on disease management using a logical model dealing with the following: case management, education and coaching, nutritional assessment, and mental health. RESULTS: The CDP improved glycemic control, HbA1c decreased by 0.56% (p-value=0.004; 95% CI: 0.14-0.98) and 19.1% of the patients reached the HbA1c goal without hypoglycemia. The CDP reduced by 52.4% the indication for SAP due to better glycemic control (36.4%) or non-adherence issues (63.6%); the remaining 47.6% persisted with poor glycemic control despite good adherence and were scaled to SAP. Among the 30 suitable candidates for SAP therapy, 60% did not reach the HbA1c goal and 40% had either hypoglycemic episodes (severe or persistent) or dawn phenomenon. The overall non-adherence rate was 33.3%. CONCLUSIONS: CDP optimized the selection of suitable candidates for SAP by improving glycemic control and identifying adherence issues early. These results provide evidence of the impact of the implementation of patient selection and educational protocols in the real-life setting of a highly experienced clinic.

The effectiveness of a comprehensive diabetes program for glycemic control and adherence, and the selection of candidates for sensor-augmented insulin pump therapy.

OBJECTIVE: This study aimed to estimate the effectiveness of a comprehensive diabetes program (CDP) in terms of glycemic control, adherence, and the selection of candidates for sensor-augmented insulin pump therapy (SAP). METHODS: We compared diabetes control before and 6 months after CDP. The program was based on disease management using a logical model dealing with the following: case management, education and coaching, nutritional assessment, and mental health. RESULTS: The CDP improved glycemic control, HbA1c decreased by 0.56% (p-value=0.004; 95% CI: 0.14-0.98) and 19.1% of the patients reached the HbA1c goal without hypoglycemia. The CDP reduced by 52.4% the indication for SAP due to better glycemic control (36.4%) or non-adherence issues (63.6%); the remaining 47.6% persisted with poor glycemic control despite good adherence and were scaled to SAP. Among the 30 suitable candidates for SAP therapy, 60% did not reach the HbA1c goal and 40% had either hypoglycemic episodes (severe or persistent) or dawn phenomenon. The overall non-adherence rate was 33.3%. CONCLUSIONS: CDP optimized the selection of suitable candidates for SAP by improving glycemic control and identifying adherence issues early. These results provide evidence of the impact of the implementation of patient selection and educational protocols in the real-life setting of a highly experienced clinic.

COVID-19 y tiroides. Revisión de la literatura y recomendaciones para pacientes con enfermedad tiroidea / Thyroid and COVID-19. Review and recommendations for patients with thyroid disease

Resumen Las enfermedades de la tiroides, tanto benignas como malignas, son altamente prevalentes a nivel mundial, por lo que es muy probable que durante la pandemia por SARS-CoV-2 veamos pacientes con ambas enfermedades. Esto exige el conocimiento de las implicaciones potenciales de este nuevo virus en el funcionamiento de la glándula, en los tratamientos usuales para estas enfermedades y en consideraciones especiales para este grupo poblacional. A la fecha no hay evidencia que soporte que las enfermedades tiroideas aumenten el riesgo de infección o severidad de la enfermedad; sin embargo, es posible que durante infecciones severas por SARS-CoV-2 en personas con o sin antecedente de enfermedad tiroidea puedan presentar alteración de las pruebas tiroideas, aunque transitoriamente y sin requerimiento de tratamiento específico. Es fundamental que los pacientes continúen con sus tratamientos ambulatorios y se difiera, en la medida de lo posible, los procedimientos quirúrgicos o la administración de yodo radioactivo hasta que se considere seguro realizarlos.

Abstract Both benign and malignant thyroid diseases are highly prevalent worldwide, so it is highly likely that during the COVID-19 pandemic we will see patients with this comorbidity. This requires knowledge of the potential implications of this new virus in the functioning of the gland, the usual treatments for these diseases and special recommendations in this population. To date, there is no evidence to support that thyroid diseases increase the risk of infection or the disease severity. However, it is possible that during severe SARS-CoV-2 infections in people with or without history of thyroid disease, the thyroid tests may be altered, although transitory and does not require specific treatment. It is essential for patients to continue with their outpatient treatments and defer as far as possible surgical procedures or administration of radioactive iodine until it is considered safe to perform.

COVID-19 y diabetes. Retos, Implicaciones y manejo durante la pandemia / COVID-19 and Diabetes. Challenges, Implications and treatment during the pandemic

Resumen Desde finales del año 2019 un nuevo coronavirus, SARS-CoV-2, se extendió desde China hacia el resto del mundo, causando la pandemia de una enfermedad denominada COVID-19. Una enfermedad sistémica que en algunos casos produce neumonía severa que incluso puede progresar a falla respiratoria aguda y finalmente la muerte. Entre las comorbilidades que se han asociado con un aumento en la mortalidad por SARS-CoV-2 se encuentra la diabetes. En general, se estima que tener diabetes aumenta un 18 % el riesgo de infecciones respiratorias, en parte por el impacto que genera sobre la inmunidad innata o adquirida, lo que estaría contribuyendo a una presentación clínica más severa del SARS-CoV-2 al comparar con población sin diabetes. Considerando que existe una asociación entre mal control glucémico y mayor severidad clínica de la infección por COVID-19, se deben hacer importantes consideraciones sobre el manejo farmacológico brindado a los pacientes; el perfilamiento dependerá de las condiciones de cada paciente, de la severidad de la enfermedad y del tipo de manejo instaurado ya sea ambulatorio o intrahospitalario.

Abstract Since the end of the year 2019 a new coronavirus called Severe Acute Respiratory Syndrome (SARS-CoV-2) has spread from China to the rest of the world, causing the pandemic of the disease called COVID-19. A systemic disease that in some cases produces severe pneumonia that can even progress to acute respiratory failure and eventually death. Among the comorbidities that have been associated with an increase in mortality from SARS-CoV-2, diabetes is one of them. In general, it is estimated that having diabetes increases the risk of respiratory infections by 18 %, in part, due to the impact on innate and acquired immunity, which would be contributing to a more severe clinical presentation of SARS-CoV-2 when compared with population without diabetes. Considering that there is an association between worse glycemic control and higher clinical severity of COVID-19 infection, important considerations must be made regarding the type of pharmacological management that is provided to patients; the profiling will depend on the conditions of each patient, the severity of the disease, and the type of management either as outpatient or in-hospital.

[Clinical impact of ertapenem de-escalation in critically-ill patients with Enterobacteriaceae infections]. / Impacto clínico del desescalamiento a ertapenem en pacientes críticos con infecciones por Enterobacteriaceae.

BACKGROUND: Ertapenem has proven to be effective for extended-spectrum beta-lactamases-producing Enterobacteriaceae but lacks activity against non-fermenters; de-escalation to this antibiotic may reduce the selection of resistance to Pseudomonas aeruginosa and improve clinical outcomes. AIM: To evaluate the clinical impact of de-escalation from broad-spectrum anti-pseudomonal agents to ertapenem, a non-pseudomonal antibiotics for Enterobacteriaceae infections in critically-ill patients. METHODS: We conducted a prospective cohort study in adult patients admitted to intensive care units (ICUs) who had Enterobacteriaceae infections and were de-escalated from empiric anti-pseudomonal coverage to non-pseudomonal antibiotics. Cox proportional hazards models were performed comparing all-cause mortality and length of hospital stay between patients who remained on anti-pseudomonal coverage versus those who were de-escalated to ertapenem. RESULTS: 105 patients in the anti-pseudomonal group were compared to 148 patients in the ertapenem de-escalation group. De-escalation was associated with lower all-cause mortality compared to patients who remained on anti-pseudomonal coverage (adjusted Hazard Ratio 0.24; 95% CI: 0.12-0.46). The length of ICU stay was similar between the groups. DISCUSSION: ICU patients with Enterobacteriaceae infections de-escalated to ertapenem therapy had better outcomes compared to patients who remained on broad-spectrum, anti-pseudomonal therapy, suggesting that de-escalation is a safe approach amongst ICU patients.

Impacto clínico del desescalamiento a ertapenem en pacientes críticos con infecciones por Enterobacteriaceae / Clinical impact of ertapenem de-escalation in critically-ill patients with Enterobacteriaceae infections

Resumen Introducción: Ertapenem ha demostrado eficacia frente a Enterobacteriaceae productoras de β-lactamasas de espectro extendido, pero carece de actividad contra bacterias no fermentadoras; el desescalamiento a este antimicrobiano cuando no existe la presencia de P. aeruginosa podría reducir la presión selectiva contra esta bacteria y mejorar los resultados clínicos. Objetivo: Evaluar el impacto clínico del desescalamiento de antimicrobianos con cobertura anti-pseudomonas a ertapenem, un agente sin este espectro, en pacientes críticos con infecciones por Enterobacteriaceae. Métodos: Se realizó un estudio de cohorte prospectivo en adultos admitidos a Unidades de Cuidado Intensivo (UCI) con infecciones por Enterobacteriaceae, que habían sido desescalados de una cobertura anti-pseudomonas, a un antimicrobiano sin la misma (ertapenem). Se realizó un modelo de riesgo proporcional de Cox comparando mortalidad por cualquier causa y duración de estancia hospitalaria entre aquellos pacientes que permanecieron con cobertura anti-pseudomonas versus aquellos que fueron desescalados a ertapenem. Resultados: 105 pacientes en el grupo anti-pseudomonas fueron comparados con 148 pacientes del grupo de desescalamiento a ertapenem. El desescalamiento estuvo asociado con una menor mortalidad por cualquier causa comparado con los pacientes que permanecieron con cobertura anti-pseudomonas (hazard ratio ajustado 0,24; IC 95%: 0,12-0,46). La estancia hospitalaria en UCI fue similar en ambos grupos. Discusión: Los pacientes de UCI con infecciones por Enterobacteriaceae desescalados a terapia con ertapenem, tuvieron mejores resultados clínicos comparados con aquellos que permanecieron en terapia anti-pseudomonas, sugiriendo que el desescalamiento es una práctica segura en esta población.

Background: Ertapenem has proven to be effective for extended-spectrum beta-lactamases-producing Enterobacteriaceae but lacks activity against non-fermenters; de-escalation to this antibiotic may reduce the selection of resistance to Pseudomonas aeruginosa and improve clinical outcomes. Aim: To evaluate the clinical impact of de-escalation from broad-spectrum anti-pseudomonal agents to ertapenem, a non-pseudomonal antibiotics for Enterobacteriaceae infections in critically-ill patients. Methods: We conducted a prospective cohort study in adult patients admitted to intensive care units (ICUs) who had Enterobacteriaceae infections and were de-escalated from empiric anti-pseudomonal coverage to non-pseudomonal antibiotics. Cox proportional hazards models were performed comparing all-cause mortality and length of hospital stay between patients who remained on anti-pseudomonal coverage versus those who were de-escalated to ertapenem. Results: 105 patients in the anti-pseudomonal group were compared to 148 patients in the ertapenem de-escalation group. De-escalation was associated with lower all-cause mortality compared to patients who remained on anti-pseudomonal coverage (adjusted Hazard Ratio 0.24; 95% CI: 0.12-0.46). The length of ICU stay was similar between the groups. Discussion: ICU patients with Enterobacteriaceae infections de-escalated to ertapenem therapy had better outcomes compared to patients who remained on broad-spectrum, anti-pseudomonal therapy, suggesting that de-escalation is a safe approach amongst ICU patients.

Role of myeloperoxidase in abdominal aortic aneurysm formation: mitigation by taurine.

Oxidative stress plays a fundamental role in abdominal aortic aneurysm (AAA) formation. Activated polymorphonuclear leukocytes (or neutrophils) are associated with AAA and express myeloperoxidase (MPO), which promotes inflammation, matrix degradation, and other pathological features of AAA, including enhanced oxidative stress through generation of reactive oxygen species. Both plasma and aortic MPO levels are elevated in patients with AAA, but the role of MPO in AAA pathogenesis has, heretofore, never been investigated. Here, we show that MPO gene deletion attenuates AAA formation in two animal models: ANG II infusion in apolipoprotein E-deficient mice and elastase perfusion in C57BL/6 mice. Oral administration of taurine [1% or 4% (wt/vol) in drinking water], an amino acid known to react rapidly with MPO-generated oxidants like hypochlorous acid, also prevented AAA formation in the ANG II and elastase models as well as the CaCl2 application model of AAA formation while reducing aortic peroxidase activity and aortic protein-bound dityrosine levels, an oxidative cross link formed by MPO. Both MPO gene deletion and taurine supplementation blunted aortic macrophage accumulation, elastin fragmentation, and matrix metalloproteinase activation, key features of AAA pathogenesis. Moreover, MPO gene deletion and taurine administration significantly attenuated the induction of serum amyloid A, which promotes ANG II-induced AAAs. These data implicate MPO in AAA pathogenesis and suggest that studies exploring whether taurine can serve as a potential therapeutic for the prevention or treatment of AAA in patients merit consideration.NEW & NOTEWORTHY Neutrophils are abundant in abdominal aortic aneurysm (AAA), and myeloperoxidase (MPO), prominently expressed in neutrophils, is associated with AAA in humans. This study demonstrates that MPO gene deletion or supplementation with the natural product taurine, which can scavenge MPO-generated oxidants, can prevent AAA formation, suggesting an attractive potential therapeutic strategy for AAA.

Optical and nuclear imaging of glioblastoma with phosphatidylserine-targeted nanovesicles.

Multimodal tumor imaging with targeted nanoparticles potentially offers both enhanced specificity and sensitivity, leading to more precise cancer diagnosis and monitoring. We describe the synthesis and characterization of phenol-substituted, lipophilic orange and far-red fluorescent dyes and a simple radioiodination procedure to generate a dual (optical and nuclear) imaging probe. MALDI-ToF analyses revealed high iodination efficiency of the lipophilic reporters, achieved by electrophilic aromatic substitution using the chloramide 1,3,4,6-tetrachloro-3α,6α-diphenyl glycoluril (Iodogen) as the oxidizing agent in an organic/aqueous co-solvent mixture. Upon conjugation of iodine-127 or iodine-124-labeled reporters to tumor-targeting SapC-DOPS nanovesicles, optical (fluorescent) and PET imaging was performed in mice bearing intracranial glioblastomas. In addition, tumor vs non-tumor (normal brain) uptake was compared using iodine-125. These data provide proof-of-principle for the potential value of SapC-DOPS for multimodal imaging of glioblastoma, the most aggressive primary brain tumor.

[Prevalence and risk factors for extended-spectrum ß-lactamase-producing Escherichia coli causing community-onset urinary tract infections in Colombia]. / Prevalencia y factores de riesgo para infecciones del tracto urinario de inicio en la comunidad causadas por Escherichia coli productor de betalactamasas de espectro extendido en Colombia.

INTRODUCTION: Urinary tract infections (UTI) are common in the community. However, information of resistant isolates in this context is limited in Latin America. This study aims to determine the prevalence and risk factors associated with community-onset UTI (CO-UTI) caused by extended-spectrum ß-lactamase (ESBL)-Producing Escherichia coli in Colombia. MATERIALS AND METHODS: A case-control study was conducted between August and December of 2011 in three Colombian tertiary-care institutions. All patients who were admitted to the Emergency Department with a probable diagnosis of CO-UTI were invited to participate. All participating patients were asked for a urine sample. ESBL confirmatory test, antibiotic susceptibility, and molecular epidemiology were performed in these E.coli isolates (Real Time-PCR for bla genes, repetitive element palindromic PCR [rep-PCR], multilocus sequence typing [MLST] and virulence factors by PCR). Clinical and epidemiological information was recorded, and a statistical analysis was performed. RESULTS: Of the 2124 recruited patients, 629 had a positive urine culture, 431 of which grew E.coli; 54 were positive for ESBL, of which 29 were CTX-M-15. The majority of ESBL isolates were susceptible to ertapenem, phosphomycin and amikacin. Complicated UTI was strongly associated with ESBL-producing E.coli infections (OR=3.89; 95%CI: 1.10-13.89; P=.03). CTX-M-15-producing E.coli showed 10 different pulsotypes, 65% were PT1 or PT4, and corresponded to ST131. Most of these isolates had 8 out of the 9 analysed virulence factors. DISCUSSION: E.coli harbouring blaCTX-M-15 associated with ST131 is still frequent in Colombia. The presence of complicated CO-UTI increases the risk of ESBL-producing E.coli, and must be taken into account in order to provide an adequate empirical therapy.

Variation in human cancer cell external phosphatidylserine is regulated by flippase activity and intracellular calcium.

Viable cancer cells expose elevated levels of phosphatidylserine (PS) on the exoplasmic face of the plasma membrane. However, the mechanisms leading to elevated PS exposure in viable cancer cells have not been defined. We previously showed that externalized PS may be used to monitor, target and kill tumor cells. In addition, PS on tumor cells is recognized by macrophages and has implications in antitumor immunity. Therefore, it is important to understand the molecular details of PS exposure on cancer cells in order to improve therapeutic targeting. Here we explored the mechanisms regulating the surface PS exposure in human cancer cells and found that differential flippase activity and intracellular calcium are the major regulators of surface PS exposure in viable human cancer cells. In general, cancer cell lines with high surface PS exhibited low flippase activity and high intracellular calcium, whereas cancer cells with low surface PS exhibited high flippase activity and low intracellular calcium. High surface PS cancer cells also had higher total cellular PS than low surface PS cells. Together, our results indicate that the amount of external PS in cancer cells is regulated by calcium dependent flippase activity and may also be influenced by total cellular PS.

Introduction of software tools for epidemiological surveillance in infection control in Colombia.

INTRODUCTION: Healthcare-Associated Infections (HAI) are a challenge for patient safety in the hospitals. Infection control committees (ICC) should follow CDC definitions when monitoring HAI. The handmade method of epidemiological surveillance (ES) may affect the sensitivity and specificity of the monitoring system, while electronic surveillance can improve the performance, quality and traceability of recorded information. OBJECTIVE: To assess the implementation of a strategy for electronic surveillance of HAI, Bacterial Resistance and Antimicrobial Consumption by the ICC of 23 high-complexity clinics and hospitals in Colombia, during the period 2012-2013. METHODS: An observational study evaluating the introduction of electronic tools in the ICC was performed; we evaluated the structure and operation of the ICC, the degree of incorporation of the software HAI Solutions and the adherence to record the required information. RESULTS: Thirty-eight percent of hospitals (8/23) had active surveillance strategies with standard criteria of the CDC, and 87% of institutions adhered to the module of identification of cases using the HAI Solutions software. In contrast, compliance with the diligence of the risk factors for device-associated HAIs was 33%. CONCLUSIONS: The introduction of ES could achieve greater adherence to a model of active surveillance, standardized and prospective, helping to improve the validity and quality of the recorded information.

INTRODUCCIÓN: Las infecciones asociadas a la atención en salud (IAAS) son un reto para la seguridad del paciente. Los comités de infecciones hospitalarios (CIH) deben realizar una vigilancia epidemiológica (VE) de las IAAS siguiendo los criterios de los Centros para el Control y Prevención de Enfermedades - EE.UU (CDC). La VE manual afecta la sensibilidad y especificidad del sistema de vigilancia, mientras que la VE electrónica mejora el desempeño, calidad y trazabilidad de la información registrada. OBJETIVO: Evaluar la implementación de una estrategia para la VE electrónica de las IAAS, resistencia bacteriana, consumo de antimicrobianos y características de los CIH en 23 clínicas y hospitales de alta complejidad en Colombia, en el periodo 2012-2013. MÉTODOS: Se realizó un estudio observacional descriptivo de la introducción de herramientas informáticas en los CIH, evaluando la estructura y funcionamiento de los CIH, el grado de incorporación del software HAI Solutions y la cumplimiento al registro de la información requerida. RESULTADOS: El 38% de las clínicas y hospitales (8/23) presentaron estrategias de vigilancia epidemiológica activa con criterios estándar del CDC. El 87% de las instituciones se adhirieron al módulo de captación de casos del software HAI Solutions, y el cumplimiento del diligenciamiento de los factores de riesgo de las IAAS asociadas a dispositivos fue del 33%. CONCLUSIONES: La introducción del modelo de VE electrónica podría lograr un mayor cumplimiento a un modelo de vigilancia epidemiológica activo, estandarizado y prospectivo, contribuyendo al mejoramiento en la validez y calidad de la información registrada.

Imaging and Therapy of Pancreatic Cancer with Phosphatidylserine-Targeted Nanovesicles.

Pancreatic cancer remains one of the most intractable cancers, with a dismal prognosis reflected by a 5-year survival of ~6%. Since early disease symptoms are undefined and specific biomarkers are lacking, about 80% of patients present with advanced, inoperable tumors that represent a daunting challenge. Despite many clinical trials, no single chemotherapy agent has been reliably associated with objective response rates above 10% or median survival longer than 5 to 7 months. Although combination chemotherapy regimens have in recent years provided some improvement, overall survival (8-11 months) remains very poor. There is therefore a critical need for novel therapies that can improve outcomes for pancreatic cancer patients. Here, we present a summary of the current therapies used in the management of advanced pancreatic cancer and review novel therapeutic strategies that target tumor biomarkers. We also describe our recent research using phosphatidylserine-targeted saposin C-coupled dioleoylphosphatidylserine nanovesicles for imaging and therapy of pancreatic cancer.

Introduction of software tools for epidemiological surveillance in infection control in Colombia / Introducción de herramientas informáticas para la vigilancia epidemiológica en el control de infecciones en Colombia

Introduction: Healthcare-Associated Infections (HAI) are a challenge for patient safety in the hospitals. Infection control committees (ICC) should follow CDC definitions when monitoring HAI. The handmade method of epidemiological surveillance (ES) may affect the sensitivity and specificity of the monitoring system, while electronic surveillance can improve the performance, quality and traceability of recorded information. Objective: To assess the implementation of a strategy for electronic surveillance of HAI, Bacterial Resistance and Antimicrobial Consumption by the ICC of 23 high-complexity clinics and hospitals in Colombia, during the period 2012-2013. Methods: An observational study evaluating the introduction of electronic tools in the ICC was performed; we evaluated the structure and operation of the ICC, the degree of incorporation of the software HAI Solutions and the adherence to record the required information. Results: Thirty-eight percent of hospitals (8/23) had active surveillance strategies with standard criteria of the CDC, and 87% of institutions adhered to the module of identification of cases using the HAI Solutions software. In contrast, compliance with the diligence of the risk factors for device-associated HAIs was 33%.

Introducción: Las infecciones asociadas a la atención en salud (IAAS) son un reto para la seguridad del paciente. Los comités de infecciones hospitalarios (CIH) deben realizar una vigilancia epidemiológica (VE) de las IAAS siguiendo los criterios de los Centros para el Control y Prevención de Enfermedades - EE.UU (CDC). La VE manual afecta la sensibilidad y especificidad del sistema de vigilancia, mientras que la VE electrónica mejora el desempeño, calidad y trazabilidad de la información registrada. Objetivo: Evaluar la implementación de una estrategia para la VE electrónica de las IAAS, resistencia bacteriana, consumo de antimicrobianos y características de los CIH en 23 clínicas y hospitales de alta complejidad en Colombia, en el periodo 2012-2013. Métodos: Se realizó un estudio observacional descriptivo de la introducción de herramientas informáticas en los CIH, evaluando la estructura y funcionamiento de los CIH, el grado de incorporación del software HAI Solutions y la cumplimiento al registro de la información requerida. Resultados: El 38% de las clínicas y hospitales (8/23) presentaron estrategias de vigilancia epidemiológica activa con criterios estándar del CDC. El 87% de las instituciones se adhirieron al módulo de captación de casos del software HAI Solutions, y el cumplimiento del diligenciamiento de los factores de riesgo de las IAAS asociadas a dispositivos fue del 33%. Conclusiones: La introducción del modelo de VE electrónica podría lograr un mayor cumplimiento a un modelo de vigilancia epidemiológica activo, estandarizado y prospectivo, contribuyendo al mejoramiento en la validez y calidad de la información registrada.

Astrocyte contributions to flow/pressure-evoked parenchymal arteriole vasoconstriction.

Basal and activity-dependent cerebral blood flow changes are coordinated by the action of critical processes, including cerebral autoregulation, endothelial-mediated signaling, and neurovascular coupling. The goal of our study was to determine whether astrocytes contribute to the regulation of parenchymal arteriole (PA) tone in response to hemodynamic stimuli (pressure/flow). Cortical PA vascular responses and astrocytic Ca(2+) dynamics were measured using an in vitro rat/mouse brain slice model of perfused/pressurized PAs; studies were supplemented with in vivo astrocytic Ca(2+) imaging. In vitro, astrocytes responded to PA flow/pressure increases with an increase in intracellular Ca(2+). Astrocytic Ca(2+) responses were corroborated in vivo, where acute systemic phenylephrine-induced increases in blood pressure evoked a significant increase in astrocytic Ca(2+). In vitro, flow/pressure-evoked vasoconstriction was blunted when the astrocytic syncytium was loaded with BAPTA (chelating intracellular Ca(2+)) and enhanced when high Ca(2+) or ATP were introduced to the astrocytic syncytium. Bath application of either the TRPV4 channel blocker HC067047 or purinergic receptor antagonist suramin blunted flow/pressure-evoked vasoconstriction, whereas K(+) and 20-HETE signaling blockade showed no effect. Importantly, we found TRPV4 channel expression to be restricted to astrocytes and not the endothelium of PA. We present evidence for a novel role of astrocytes in PA flow/pressure-evoked vasoconstriction. Our data suggest that astrocytic TRPV4 channels are key molecular sensors of hemodynamic stimuli and that a purinergic, glial-derived signal contributes to flow/pressure-induced adjustments in PA tone. Together our results support bidirectional signaling within the neurovascular unit and astrocytes as key modulators of PA tone.

SapC-DOPS nanovesicles induce Smac- and Bax-dependent apoptosis through mitochondrial activation in neuroblastomas.

BACKGROUND: High toxicity, morbidity and secondary malignancy render chemotherapy of neuroblastoma inefficient, prompting the search for novel compounds. Nanovesicles offer great promise in imaging and treatment of cancer. SapC-DOPS, a stable nanovesicle formed from the lysosomal protein saposin C and dioleoylphosphatidylserine possess strong affinity for abundantly exposed surface phosphatidylserine on cancer cells. Here, we show that SapC-DOPS effectively targets and suppresses neuroblastoma growth and elucidate the molecular mechanism of SapC-DOPS action in neuroblastoma in vitro. METHODS: In vivo targeting of neuroblastoma was assessed in xenograft mice injected intravenously with fluorescently-labeled SapC-DOPS. Xenografted tumors were also used to demonstrate its therapeutic efficacy. Apoptosis induction in vivo was evaluated in tumor sections using the TUNEL assay. The mechanisms underlying the induction of apoptosis by SapC-DOPS were addressed through measurements of cell viability, mitochondrial membrane potential (ΔΨM), flow cytometric DNA fragmentation assays and by immunoblot analysis of second mitochondria-derived activator of caspases (Smac), Bax, Cytochrome c (Cyto c) and Caspase-3 in the cytosol or in mitochondrial fractions of cultured neuroblastoma cells. RESULTS: SapC-DOPS showed specific targeting and prevented the growth of human neuroblastoma xenografts in mice. In neuroblastoma cells in vitro, apoptosis occurred via a series of steps that included: (1) loss of ΔΨM and increased mitochondrial superoxide formation; (2) cytosolic release of Smac, Cyto c, AIF; and (3) mitochondrial translocation and polymerization of Bax. ShRNA-mediated Smac knockdown and V5 peptide-mediated Bax inhibition decreased cytosolic Smac and Cyto c release along with caspase activation and abrogated apoptosis, indicating that Smac and Bax are critical mediators of SapC-DOPS action. Similarly, pretreatment with the mitochondria-stabilizing agent bongkrekic acid decreased apoptosis indicating that loss of ΔΨM is critical for SapC-DOPS activity. Apoptosis induction was not critically dependent on reactive oxygen species (ROS) production and Cyclophilin D, since pretreatment with N-acetyl cysteine and cyclosporine A, respectively, did not prevent Smac or Cyto c release. CONCLUSIONS: Taken together, our results indicate that SapC-DOPS acts through a mitochondria-mediated pathway accompanied by an early release of Smac and Bax. Specific tumor-targeting capacity and anticancer efficacy of SapC-DOPS supports its potential as a dual imaging and therapeutic agent in neuroblastoma therapy.

SapC-DOPS nanovesicles: a novel targeted agent for the imaging and treatment of glioblastoma.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor. Classified by the World Health Organization (WHO) as grade IV astrocytoma, GBMs are extremely aggressive, almost always recur, and despite our best efforts, remain incurable. This review describes the traditional treatment approaches that led to moderate successes in GBM patients, discusses standard imaging modalities, and presents data supporting the use of SapC-DOPS, a novel proteoliposomal formulation with tumoricidal activity, as a promising diagnostic imaging tool and an innovative anti-cancer agent against GBM.

SapC-DOPS nanovesicles as targeted therapy for lung cancer.

Lung cancer is the deadliest type of cancer for both men and women. In this study, we evaluate the in vitro and in vivo efficacy of a biotherapeutic agent composed of a lysosomal protein (Saposin C, SapC) and a phospholipid (dioleoylphosphatidylserine, DOPS), which can be assembled into nanovesicles (SapC-DOPS) with selective antitumor activity. SapC-DOPS targets phosphatidylserine, an anionic phospholipid preferentially exposed in the surface of cancer cells and tumor-associated vasculature. Because binding of SapC to phosphatidylserine is favored at acidic pHs, and the latter characterizes the milieu of many solid tumors, we tested the effect of pH on the binding capacity of SapC-DOPS to lung tumor cells. Results showed that SapC-DOPS binding to cancer cells was more pronounced at low pH. Viability assays on a panel of human lung tumor cells showed that SapC-DOPS cytotoxicity was positively correlated with cell surface phosphatidylserine levels, whereas mitochondrial membrane potential measurements were consistent with apoptosis-related cell death. Using a fluorescence tracking method in live mice, we show that SapC-DOPS specifically targets human lung cancer xenografts, and that systemic therapy with SapC-DOPS induces tumor apoptosis and significantly inhibits tumor growth. These results suggest that SapC-DOPS nanovesicles are a promising treatment option for lung cancer.

Dissemination of high-risk clones of extensively drug-resistant Pseudomonas aeruginosa in colombia.

The ability of Pseudomonas aeruginosa to develop resistance to most antimicrobials represents an important clinical threat worldwide. We report the dissemination in several Colombian hospitals of two predominant lineages of extensively drug-resistant (XDR) carbapenemase-producing P. aeruginosa strains. These lineages belong to the high-risk clones sequence type 111 (ST111) and ST235 and harbor blaVIM-2 on a class 1 integron and blaKPC-2 on a Tn4401 transposon, respectively. Additionally, P. aeruginosa ST1492, a novel single-locus variant of ST111, was identified. Clonal dissemination and the presence of mobile genetic elements likely explain the successful spread of XDR P. aeruginosa strains in Colombia.

Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors.

Brain tumors, either primary (e.g., glioblastoma multiforme) or secondary (metastatic), remain among the most intractable and fatal of all cancers. We have shown that nanovesicles consisting of Saposin C (SapC) and dioleylphosphatidylserine (DOPS) are able to effectively target and kill cancer cells both in vitro and in vivo. These actions are a consequence of the affinity of SapC-DOPS for phosphatidylserine, an acidic phospholipid abundantly present in the outer membrane of a variety of tumor cells and tumor-associated vasculature. In this study, we first characterize SapC-DOPS bioavailability and antitumor effects on human glioblastoma xenografts, and confirm SapC-DOPS specificity towards phosphatidylserine by showing that glioblastoma targeting is abrogated after in vivo exposure to lactadherin, which binds phosphatidylserine with high affinity. Second, we demonstrate that SapC-DOPS selectively targets brain metastases-forming cancer cells both in vitro, in co-cultures with human astrocytes, and in vivo, in mouse models of brain metastases derived from human breast or lung cancer cells. Third, we demonstrate that SapC-DOPS have cytotoxic activity against metastatic breast cancer cells in vitro, and prolong the survival of mice harboring brain metastases. Taken together, these results support the potential of SapC-DOPS for the diagnosis and therapy of primary and metastatic brain tumors.