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.

Objective This study investigated the role of oxidative damage and nitric oxide (NO) synthases in the fetal heart using a model of intrauterine growth restriction induced by uteroplacental circulation restriction (UCR). Methods New Zealand white rabbits kept under 12-h light cycles, with food and water provided ad libitum, were subjected at day 25 of pregnancy to 40–50% uteroplacental artery ligation. We analyzed the gene expression of enzymes linked to nitric oxide synthesis (iNOS, eNOS, HO-1, and ARG-2), hypoxia inducible factor 1 alpha (HIF-1α), and the state of oxidative stress (protein carbonyl levels) in fetal heart homogenates. Additionally, we studied the histological morphology of the fetal heart. Results We found that fetal growth restriction was associated with a significant reduction in heart weight but a normal heart/body weight ratio in UCR animals. Hematoxylin and eosin staining showed normal left and right ventricular thickness but increased vessel dilatation with hyperemia in the hearts of the UCR group. We observed HIF-1α, eNOS, p-eNOS, and iNOS induction concomitant with intensified protein carbonyl levels but observed no changes in HO-1 or ARG-2 expression, suggesting increased NO and oxidative stress in the hearts of UCR animals. Conclusion Uteroplacental circulation restriction increased NO-linked enzymes, oxidative damage, and dilated coronary vessels in fetal hearts.

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.

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

Objective: Telemedicine arises as an attractive intervention for reducing the waiting time for appointments with medical specialists in Chile. Successful implementation of this technology requires safeguarding the patient/clinician trust relationship; however, no studies have been conducted to evaluate quality perception of a telemedicine program in Chile. To assess patient satisfaction with the Teleneurology program at the Hospital Higueras Talcahuano (HHT), addressing patient/clinician trust relationship. Results: A perception survey was constructed with 23 questions, distributed into 5 key areas (items) of user satisfaction. Its face validity was performed by five neurology specialists from the Teleneurology unit of HHT. The survey was applied to 167 patients of the HHT, recruited between 2018 and 2019, for conducting a pilot cross-sectional descriptive study to assess internal consistency (Cronbach alpha) and reliability (factorial analysis of main components). The survey showed an internal consistency of 0.88. Removing any of the items maintained its reliability in values over 0.8. All items showed point biserial correlations greater than 0.30. Overall, the survey constructed and evaluated in this study showed high internal consistency and reliability values, which will allow its application in further studies of quality assessment of the Teleneurology unit of HHT.

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.

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.

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.

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/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.