Dr. Alvarado-Livacic, Cristobal

Oxidative stress produces macromolecules dysfunction and cellular damage. Renal ischemia-reperfusion injury (IRI) induces oxidative stress, inflammation, epithelium and endothelium damage, and cessation of renal function. The IRI is an inevitable process during kidney transplantation. Preliminary studies suggest that aminoguanidine (AG) is an antioxidant compound. In this study, we investigated the antioxidant effects of AG (50 mg/kg, intraperitoneal) and its association with molecular pathways activated by IRI (30 min/48 h) in the kidney. The antioxidant effect of AG was studied measuring GSSH/GSSG ratio, GST activity, lipoperoxidation, iNOS, and Hsp27 levels. In addition, we examined the effect of AG on elements associated with cell survival, inflammation, endothelium, and mesenchymal transition during IRI. AG prevented lipid peroxidation, increased GSH levels, and recovered the GST activity impaired by IRI. AG was associated with inhibition of iNOS, Hsp27, endothelial activation (VE-cadherin, PECAM), mesenchymal markers (vimentin, fascin, and HSP47), and inflammation (IL-1β, IL-6, Foxp3, and IL-10) upregulation. In addition, AG reduced kidney injury (NGAL, clusterin, Arg-2, and TFG-β1) and improved kidney function (glomerular filtration rate) during IRI. In conclusion, we found new evidence of the antioxidant properties of AG as a renoprotective compound during IRI. Therefore, AG is a promising compound to treat the deleterious effect of renal IRI.

Background/Aims: Renal ischemia and reperfusion injury (IRI) involves oxidative stress, disruption of microvasculature due to endothelial cell damage, loss of epithelial cell polarity secondary to cytoskeletal alterations, inflammation, and the subsequent transition into a mesenchymal phenotype. Ischemic preconditioning (IPC) has been proposed as a therapeutic strategy to avoid/ameliorate the IRI. Since previous results showed that IPC could have differential effects in kidney cortex vs. kidney medulla, in the present study we analyzed the effectiveness and molecular mechanisms implicated in IPC in both kidney regions. Methods: We evaluated 3 experimental groups of BALB/c male mice: control (sham surgery); renal ischemia (30 min) by bilateral occlusion of the renal pedicle and reperfusion (48 hours) (I/R); and renal IPC (two cycles of 5 min of ischemia and 5 min of reperfusion) applied just before I/R. Acute kidney injury was evaluated by glomerular filtration rate (GFR), Neutrophil Gelatinase-Associated Lipocalin (NGAL) blood level, and histologic analysis. Oxidative stress was studied measurement the Glutathione S-Transferase (GST) activity, GSH/GSSG ratio, and lipoperoxidation levels. Inflammatory mediators (IL-1β, IL-6, Foxp3, and IL-10) were quantified by qRT-PCR. The endothelial (PECAM-1), epithelial (AQP-1), mesenchymal (Vimentin, Fascin, and Hsp47), iNOS, clusterin, and Hsp27 expression were evaluated (qRT-PCR and/or Western blot). Results: The IPC protocol prevented the decrease of GFR, reduced the plasma NGAL, and ameliorated morphological damage in the kidney cortex after I/R. The IPC also prevented the downregulation of GST activity, lipoperoxidation and ameliorated the oxidized glutathione. In addition, IPC prevented the upregulation of vimentin, fascin, and Hsp47, which was associated with the prevention of the downregulation of AQP1 after I/R. The protective effect of IPC was associated with the upregulation of Hsp27, Foxp3, and IL-10 expression in the renal cortex. However, the upregulation of iNOS, IL-1β, IL-6, and clusterin by I/R were not modified by IPC. Conclusion: IPC conferred better protection in the kidney cortex as compared to the kidney medulla. The protective effect of IPC was associated with amelioration of oxidative stress, tubular damage, and the induction of markers of Treg lymphocytes activity in the cortical region. Further studies are needed to evaluate if lower tubular cell stress/damage after I/R may explain the preferential induction of Treg response in the kidney cortex induced by IPC.

Background: In those patients who do not have timely access to primary angioplasty, the pharmaco-invasive approach, that is, the use of thrombolysis as a bridging measure prior to the coronary angiography, is a safe alternative. Aim: To describe the features of patients with an acute ST-elevation myocardial infarction (STEMI) treated with a pharmaco-invasive strategy. Material and Methods: Descriptive observational study of 144 patients with mean age of 46 years with STEMI who received a dose of thrombolytic prior to their referral for primary angioplasty at a public hospital between 2018 and 2021. Results: There were no differences the clinical presentation according to the Killip score at admission between thrombolyzed and non-thrombolyzed patients (p = ns). Fifty-three percent of non-thrombolyzed patients were admitted with an occluded vessel (TIMI 0) compared with 27% of thrombolyzed patients (p < 0.001). The thrombolyzed group required significantly less use of thromboaspiration (3.5 and 8.4% respectively; p = 0.014). Despite this, 91 and 92% of non-thrombolyzed and thrombolyzed patients achieved a post-angioplasty TIMI 3 flow. Long-term survival was 91 and 86% in thrombolyzed and non-thrombolyzed patients, respectively (p = ns). Conclusions: The pharmaco-invasive strategy is a safe alternative when compared to primary angioplasty in centers that don`t have timely access to Interventional Cardiology.

La Telemedicina es la entrega remota de servicios de atención médica e información clínica utilizando tecnología de telecomunicaciones. La pandemia de SARS-CoV-2 ha catalizado la adopción de esta estrategia. En esta revisión analizamos su desarrollo local, considerando como modelo la Unidad de Teleprocesos del hospital Las Higueras de Talcahuano (HHT) en conjunto con la Unidad de Neurología (UN). Demostramos alta satisfacción usuaria, reducción en lista de espera de primera consulta, cobertura de la enfermedad neurológica ambulatoria y alto nivel de resolutividad. Esta experiencia ofrece una alternativa para mejorar la resolutividad médica a nivel nacional y mejorar la eficacia del sistema de salud especialmente en los nuevos escenarios causados por la pandemia. Finalmente, exponemos nuestras nuevas acciones centradas en educación, seguimiento de pacientes SARS-CoV-2 positivos y contactos estrechos, ampliación de prestaciones telemédicas a domicilio y creación de plataforma web junto a la comunidad.

Introduction: Extracorporeal membrane oxygenation (ECMO) is the first-line therapy for temporary mechanical circulatory support allowing cardiac and pulmonary recovery or as a bridge to further therapeutic alternatives. The aim of this study was to report clinical outcomes in adult patients with refractory cardiac failure after open-heart surgery undergoing ECMO in a single center with an ECMO unit in Chile. Methods: We retrospectively analyzed adults with refractory cardiac failure after open-heart surgery who required a venoarterial (VA) ECMO between 2016 and 2021. Results: Of 16 patients with VA ECMO, 60% were men (n=10), 90% had hypertension (n=14), 69% had < 30% of left ventricular ejection fraction (n=11), and the mean European System for Cardiac Operative Risk Evaluation II score was 12 ± 11%. ECMO support with central cannulation accounts for 81% (n=13), and an intra-aortic balloon pump was used in nine patients (56%). The mean time of support was 4.7 ± 2.6 days (1.5 – 12 days). ECMO weaning was achieved in 88% of patients, and in-hospital mortality was 44% (n=7) after discharge. The freedom from all-cause mortality at one year of follow-up of the entire cohort was 38% (n=6). Conclusion: VA ECMO is now a well-known life-saving therapeutic option, but mortality and morbidity remain high. Implementation of an ECMO program with educational training is mandatory in order to find the proper balance between patient benefits, ethical considerations, and public health financial input in South America

Background: Chile has a shortage of medical experts, including neurologists. The remote neurology program at Las Higueras Hospital in Talcahuano (HHT) was implemented in 2015 to decrease the number of patients waiting for their first appointment. Methods: This retrospective study analyzed a cohort of 2,904 ambulatory patients evaluated in the teleneurology program at the HHT between 2015 and 2019 who were referred from 16 primary and 3 tertiary healthcare centers. Results: Out of the 2,904 patients included in the study, 1,020 patients (35%) were male, and 1,884 (65%) were female. In total, 1,346 (46.0%) patients were under 60 years old (408 male and 938 female), and 1,558 (54%) were over 60 years old (612 male and 946 female). The patients were referred to a neurologist in the teleneurology program from different primary healthcare centers (93.5%) and tertiary healthcare centers (6.5%). The most common diseases diagnosed through teleneurology were, in decreasing order, headache (29.4%), Alzheimer's disease and other dementias (15.9%), and epilepsy (11.4%). From July 2018, we analyzed the patients' destination after the first teleneurology consultation. In the cohort of 634 patients who had their first consultation via the teleneurology program, 547 (86.3%) were instructed to continue follow-up via telemedicine. Conclusions: Data from this study show, for the first time in Chile, the significant contribution of the teleneurology program at the HHT to the diagnosis of a broad range of diseases in a substantial number of patients referred from primary and tertiary healthcare centers.

Background: The quality assessment of the home-based isolation and care program (HBIC) relies heavily on patient satisfaction and length of stay. COVID-19 patients who were isolated and received HBIC were monitored through telephone consultations (TC), in-person TC visits, and a self-reporting application. By evaluating patient satisfaction and length of stay in HBIC, healthcare providers could gauge the effectiveness and efficiency of the HBIC program. Methods: A cross-sectional study design enrolled 444 HBIC patients who answered a structured questionnaire. A binary logistic regression model assessed the association between independent variables and patient satisfaction. The length of stay in HBIC was analyzed using Cox regression analysis. The data collection started on April (1–30), 2022, in Addis Ababa, Ethiopia. Results: The median age was 34, and 247 (55.6%) were females. A greater proportion (313, 70.5%) of the participants had high satisfaction. Higher frequency of calls (&gt;3 calls) (AOR = 2.827, 95% CI = 1.798, 4.443, p = 0.000) and those who were symptomatic (AOR = 2.001, 95% CI = 1.289, 3.106, p = 0.002) were found to be significant factors for high user satisfaction. Higher frequency of calls (&gt;3 calls) (AHR = 0.537, 95% CI = 0.415, 0.696, p = 0.000) and more in-person visits (&gt;1 visit) (AHR = 0.495, 95% CI = 0.322, 0.762, p = 0.001) had greater chances to reduce the length of stay in the COVID-19 HBIC. Conclusion: 70.5% of the participants had high satisfaction with the system, and frequent phone call follow-ups on patients’ clinical status can significantly improve their satisfaction and length of recovery. An in-person visit is also an invaluable factor in a patient’s recovery.

Introducción: En los pacientes críticos con COVID-19 ocurren una serie de alteraciones metabólicas, las cuales afectan directamente el estado nutricional del paciente. Para mejorar la sobrevida de los pacientes con COVID-19, se hace relevante el tratamiento nutricional oportuno, idealmente dentro de las primeras 24-48 horas de la admisión a la UCI. El objetivo de este estudio fue reportar la evolución, desde el ingreso hasta el egreso, del balance nitrogenado, diversos parámetros bioquímicos y el estado nutricional de los pacientes con neumonía por COVID-19. Método: Estudio observacional retrospectivo de temporalidad longitudinal, se realizó en la UCI del Hospital Las Higueras de Talcahuano, Chile. Se incluyeron a 33 pacientes al ingreso y al egreso de la UCI. Resultados: Se reportó un incremento significativo del balance nitrogenado al egreso de los pacientes de UCI, sin embargo, no se registraron cambios en la media de talla, peso, IMC, prevalencia de desnutrición durante la estancia en la UCI. La prevalencia de desnutrición moderada y severa fue de un 14,0%, valor inferior al 45,0% informado en pacientes con COVID-19. Conclusión: En este estudio se reportó que la implementación del protocolo y la terapia nutricionales durante la pandemia de COVID-19 se asoció a un aumento del balance nitrogenado y un mejor control glicémico en los pacientes que egresan de la UCI por neumonía de COVID-19.

Backround: There is a shortage of medical specialists in Chile, including neurologists; currently, there are 56,614 patients waiting for a first adult Neurology appointment in the country. The Teleneurology Program at the Hospital Las Higueras de Talcahuano (HHT) was implemented in 2015 to help reduce both the number of patients waiting for a first consultation and their waiting times. Methods: This retrospective study analyzed a cohort of 8269 patients referred to the HHT Neurology clinic between 2013 and 2018, from primary, secondary, and tertiary health centers. Cox regression analyses were performed to determine the factors influencing each outcome (number of patients waiting for a consultation and waiting time), such as age, gender, referral health establishment and the type of consultation (whether in situ at the HHT or by synchronic telepresence through the Teleneurology Program). Results: Out of the 8269 patients included in the study, 1743 consulted the neurologist through the Teleneurology Program, while 6526 received a consultation in situ at the HHT. Since its implementation (2015) until the end of 2018, the Teleneurology program contributed to decrease the number of patients waiting for their first appointment from 3084 to 298. Waiting time for the first consultation was 60% shorter for patients enrolled in the Teleneurology program than those with consultation in situ at HHT (6.23 ± 6.82 and 10.47 ± 8.70 months, respectively). Similar differences were observed when sorting patient data according to the referral health center. Cox regression analysis showed that patients waiting for a traditional in situ first adult Neurology consultation at the HHT had a higher risk (OR = 6.74) of waiting 90% longer than patients enrolled in the Teleneurology Program, without significant differences due to gender or age. Conclusions: Data from this study show a significant contribution of the Teleneurology Program at the HHT to decrease the number of patients waiting for a first consultation with a neurologist, as well as shorter waiting times, when derived from primary and secondary health centers.

Introduction: The use of biological valves in the aortic position has become more liberal in recent years due to improvements in prostheses and the possibility of performing valve-in-valve procedures, thus avoiding anticoagulation. Methods: We retrospectively evaluated 246 adults in whom the Crown PRTTM biological valve was used in the aortic position, including elective and emergency cases, isolated and combined surgeries (CS). We also evaluated mortality at 1, 3, and 5 years of follow-up. Results: In this study, CS involved 94 patients (38%), while 39 patients (16%) underwent urgent or emergency procedures, which included cases of aortic dissection and endocarditis. Approximately 69% of the patients received a valve more significant than 21 mm. A minimally invasive surgical approach was employed in 42 patients (17%). The in-hospital mortality for the entire patient population was 3.6% (n = 9), with isolated aortic valve replacement (AVR) accounting for 3.3% (n = 5) and CS for another 4.3% (n = 4). The mortality for isolated AVR and CS in elective situations was n = 2 (1.3%) and n = 1 (1.1%), respectively. During the follow-up period, only seven patients required reoperation, with two patients (0.8%) experiencing structural valve deterioration and five other patients (2.1%) requiring reoperation due to prosthetic valve endocarditis. Conclusion: The use of the Crown valve in the aortic position appears to be safe regarding postoperative morbidity and mortality. Further studies are necessary to assess its applicability in younger patients and predict its performance in the event of a valve-in-valve procedure.