Artículos Medicina y Ciencias de la Salud

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24/7 Physical Therapy Intervention With Adult Patients in a Chilean Intensive Care Unit: A Cost-Benefit Analysis in a Developing Country
(2020) Merino, Catalina; Velásquez, Mónica; Marmolejo, José Ignacio; Fu, Carolina
Objectives: Physiotherapy in an adult intensive care unit (ICU) affects health outcome. To justify the investment in ICU physical therapy, the cost savings associated with its benefits need to be established. The main objective of this study is to evaluate the potential cost savings of implementing 24-hour, 7-days-per-week physiotherapist (24/7-PT) in a Chilean public high-complex specialized ICU. Methods: Using clinical data from a literature review and a micro-costing technique, we conducted a cost-benefit analysis in the National Institute of Thorax in Chile. Our example scenario involves 697 theoretical admissions of adult patients with cardiovascular or respiratory diseases, and the costs and benefits by reduction of length of stay in ICU, days of mechanical ventilation, and days with respiratory infections during the first year and 5 years of admissions. A sensitivity analysis was considered according to the variability in total costs, production income, and clinical benefits. Results: Net cost savings generated in our example scenario demonstrate that the implementation of 24/7-PT produces a minimum saving for the institution of $16 242 during the first year and $69 351 over a 5-year interval considering individual income production. Out of the 30 scenarios included in the sensitivity analyses, 26 (87%) demonstrated net savings. Conclusions: A financial model, based on literature review and actual cost data, projects that 24/7-PT intervention is a costbenefit alternative in adult ICU patients with cardiovascular or respiratory diseases in Chile. It is necessary a scenario of at least 3 sessions per day with insurance payment for individual treatments to support the long-term implementation of a 24/7-PT program.
3D-printed hand prostheses function in adolescents with congenital hand amputation: a case series
(2020) Dote, Jacqueline; Nahuelhual, Paula; Cubillos, Rodrigo; Fuentes, Gabriel; Zuniga, Jorge
Objective: To describe the effect of the 3D-printed Cyborg Beast prosthesis on upper limbs function in adolescents with congenital hand amputation. Clinical Cases: Five patients aged between 12 and 17 years, with congenital hand amputation were selected. All patients were from the Teletón Institute in Santiago, Chile. The patients were trained for prosthesis use in four sessions. Hand function was evaluated without prosthesis, at 1 and 4 months of use with the modified Bilan 400 points scale, and upper limb function perception was evaluated with the ’Upper Extremity Functional Index (UEFI)’. At 1 month and 4 months of use, the percentage change for hand functionality for the unaffected limbs was between -11% and -4%; and -9% and -2% for the affected limb. The percentage change for the upper limbs perceived function was -62%. Conclusions: The use of the 3D-printed Cyborg Beast prosthesis was not a functional solution for the 5 patients included in this study. Future research is needed to improve the functionality of these types of 3D-printed hand prostheses.
4-Hydroxynonenal induces Cx46 hemichannel inhibition through its carbonylation
(2020) Retamal, Mauricio; Fiori, Mariana C.; Fernández-Olivares, Ainoa; Linsambarth, Sergio; Peña, Francisca; Quintana, Daisy; Stehberg, Jimmy; Altenberg, Guillermo A.
Hemichannels formed by connexins mediate the exchange of ions and signaling molecules between the cytoplasm and the extracellular milieu. Under physiological conditions hemichannels have a low open probability, but in certain pathologies their open probability increases, which can result in cell damage. Pathological conditions are characterized by the production of a number of proinflammatory molecules, including 4-hydroxynonenal (4-HNE), one of the most common lipid peroxides produced in response to inflammation and oxidative stress. The aim of this work was to evaluate whether 4-HNE modulates the activity of Cx46 hemichannels. We found that 4-HNE (100 μM) reduced the rate of 4′,6-diamino-2-fenilindol (DAPI) uptake through hemichannels formed by recombinant human Cx46 fused to green fluorescent protein, an inhibition that was reversed partially by 10 mM dithiothreitol. Immunoblot analysis showed that the recombinant Cx46 expressed in HeLa cells becomes carbonylated after exposure to 4-HNE, and that 10 mM dithiothreitol reduced its carbonylation. We also found that Cx46 was carbonylated by 4-HNE in the lens of a selenite-induced cataract animal model. The exposure to 100 μM 4-HNE decreased hemichannel currents formed by recombinant rat Cx46 in Xenopus laevis oocytes. This inhibition also occurred in a mutant expressing only the extracellular loop cysteines, suggesting that other Cys are not responsible for the hemichannel inhibition by carbonylation. This work demonstrates for the first time that Cx46 is post-translationally modified by a lipid peroxide and that this modification reduces Cx46 hemichannel activity.
5,926 hysterectomies: complications described by Clavien–Dindo classification
(2021) Alliende, Rodrigo; Carrasco, Álvaro; Levancini, Marco; Kovoor, Elias; Guzmán Rojas, Rodrigo; Miranda, Ignacio
Hysterectomy is the most common major gynaecological surgery. Due to its high volume, the analysis of its results is relevant. The objective of this study was to describe intraoperative complications and reoperations, for both benign and malignant causes, using the Clavien–Dindo classification (approved by local ethics committee, number 100220). Between 2000 and 2019, 5926 elective hysterectomies were performed, of which 90.2% were for benign aetiology and 9.8% for malignant causes. The abdominal route was 52.7%, vaginal 40.1% and laparoscopic 7.2%. Intraoperative complications and reoperations (grade III Clavien–Dindo) were 4% and 2.1%, respectively. Oncological surgery had significantly more intraoperative complications (10% vs. 3.4%) and reoperations (3.6% vs. 1.9%) than benign procedures. Noteworthy, intraoperative complications required a new operation in only 3.4% for malignant and 2.8% for benign surgery. Our data showed the relevance of detecting and rectifying intraoperative complications during surgery, which consequently leads to a lower reoperation rate, minimising postoperative morbidity and mortality for patients.
A 10-gene classifier for indeterminate thyroid nodules: development and multicenter accuracy study
(American Thyroid Association, 2017) González, Hernán; Martínez, José R.; Vargas, Sergio; Solar, Antonieta; Veliz, Loreto; Cruz, Francisco; Arias, Tatiana; Loyola, Soledad; Horvath, Eleonora; Tala, Hernán; Traipe, Eufrosina; Meneses, Manuel; Marín, Luis; Wohllk, Nelson; Diaz, René; Véliz, Jesús; Pineda, Pedro; Arroyo, Patricia; Mena, Natalia; Bracamonte, Milagros; Miranda, Giovanna; Bruce, Elsa; Urra, Soledad
BACKGROUND: In most of the world, diagnostic surgery remains the most frequent approach for indeterminate thyroid cytology. Although several molecular tests are available for testing in centralized commercial laboratories in the United States, there are no available kits for local laboratory testing. The aim of this study was to develop a prototype in vitro diagnostic (IVD) gene classifier for the further characterization of nodules with an indeterminate thyroid cytology. METHODS: In a first stage, the expression of 18 genes was determined by quantitative polymerase chain reaction (qPCR) in a broad histopathological spectrum of 114 fresh-tissue biopsies. Expression data were used to train several classifiers by supervised machine learning approaches. Classifiers were tested in an independent set of 139 samples. In a second stage, the best classifier was chosen as a model to develop a multiplexed-qPCR IVD prototype assay, which was tested in a prospective multicenter cohort of fine-needle aspiration biopsies. RESULTS: In tissue biopsies, the best classifier, using only 10 genes, reached an optimal and consistent performance in the ninefold cross-validated testing set (sensitivity 93% and specificity 81%). In the multicenter cohort of fine-needle aspiration biopsy samples, the 10-gene signature, built into a multiplexed-qPCR IVD prototype, showed an area under the curve of 0.97, a positive predictive value of 78%, and a negative predictive value of 98%. By Bayes' theorem, the IVD prototype is expected to achieve a positive predictive value of 64-82% and a negative predictive value of 97-99% in patients with a cancer prevalence range of 20-40%. CONCLUSIONS: A new multiplexed-qPCR IVD prototype is reported that accurately classifies thyroid nodules and may provide a future solution suitable for local reference laboratory testing.
A 12-month prospective study on the time to hospitalization and clinical management of a cohort of bipolar type I and schizoaffective bipolar patients
(Elsevier Masson SAS, 2019-09) Murru, Andrea; Verdolini, Norma; Anmella, Gerard; Pacchiarotti, Isabella; Samalin, Ludovic; Aedo, Alberto; Undurraga, Juan; Goikolea, José; Benedikt, Amann; Carvalho, Andre; Vieta, Eduard
Background: Schizoaffective disorder, bipolar type (SAD) and bipolar disorder I (BD) present a large clinical overlap. In a 1-year follow-up, we aimed to evaluate days to hospitalization (DTH) and predictors of relapse in a SAD-BD cohort of patients. Methods: A 1-year, prospective, naturalistic cohort study considering DTH as primary outcome and incidence of direct and indirect measures of psychopathological compensation as secondary outcomes. Kaplan-Meyer survival analysis with Log-rank Mantel-Cox test compared BD/SAD subgroups as to DTH. After bivariate analyses, Cox regression was performed to assess covariates possibly associated with DTH in diagnostic subgroups. Results: Of 836 screened patients, 437 were finally included (SAD = 105; BD = 332). Relapse rates in the SAD sample was n = 26 (24.8%) vs. n = 41 (12.3%) in the BD sample (p = 0.002). Mean ± SD DTH were 312.16 ± 10.6 (SAD) vs. 337.62 ± 4.4 (BD) days (p = 0.002). Patients with relapses showed more frequent suicide acts, violent behaviors, and changes in pharmacological treatments (all p < 0.0005) in comparison to patients without relapse. Patients without relapses had significantly higher mean number of treatments at T0 (p = 0.010). Cox regression model relating the association between diagnosis and DTH revealed that BD had higher rates of suicide attempts (HR = 13.0, 95%CI = 4.0-42.0, p < 0.0005), whereas SAD had higher rates of violent behavior during psychotic episodes (HR = 12.0, 95%CI = .3.3-43.5, p > 0.0005). Conclusions: SAD patients relapse earlier with higher hospitalization rates and violent behavior during psychotic episodes whereas bipolar patients have more suicide attempts. Psychiatric/psychological follow-up visits may delay hospitalizations by closely monitoring symptoms of self- and hetero-aggression.
A 19 Year Analysis of Small Mammals Associated with Human Hantavirus Cases in Chile
(2019) Torrez-Pérez, Fernando; Palma, Eduardo; Boric-Bargetto, Dusan; Vial, Cecilia; Ferrés, Marcela; Vial, Pablo; Martínez-Valdebenito, Constanza; Pavletic, Carlos; Parra, Alonso; Marquet, Pablo; Mertz, Gregory
Small mammals present in areas where hantavirus cardiopulmonary syndrome (HCPS) cases had occurred in central and southern Chile were captured and analyzed to evaluate theabundance of rodents and seroprevalence rates of antibodies to Andes orthohantavirus (ANDV). Sampling areas ranged from the Coquimbo to Aysén regions (30–45° S approx.) regions. Ninetytwo sites in peridomestic and countryside areas were evaluated in 19 years of sampling. An antibody against ANDV was detected by strip immunoassay in 58 of 1847 specimens captured using Sherman traps. Of the eleven species of rodents sampled, Abrothrix olivacea, Oligoryzomys longicaudatus and Abrothrix hirta were the most frequently trapped. O. longicaudatus had the highest seropositivity rate, and by logistic regression analysis, O. longicaudatus of at least 60 g had 80% or higher probability to be seropositive. Sex, age and wounds were significantly related to seropositivity only for O. longicaudatus. Across administrative regions, the highest seropositivity was found in the El Maule region (34.8–36.2° S), and the highest number of HCPS cases was registered in the Aysén region. Our results highlight the importance of long term and geographically extended studies, particularly for highly fluctuating pathogens and their reservoirs, to understand the implications of the dynamics and transmission of zoonotic diseases in human populations.
A 37-year-old woman with dyspnea and stridor
(American Thoracic Society, 2016) Gando, Sebastian; Garcia, Ana; Labarca, Gonzalo; Fernández-Bussy, Sebastián
A woman with morbid obesity and a diagnosis of asthma since childhood sought medical attention because of unrelenting dyspnea and nocturnal stridor. Spirometry revealed a restrictive pattern with amputation of inspiratory and expiratory maximum flow rates. She was referred for further diagnostic evaluation.
A Case of Interstitial Lung Disease With Apical Pleural Thickening: Idiopathic Pleuroparenchymal Fibroelastosis
(Sociedad Española de Neumología y Cirugia Torácica, 2014) Labarca, Gonzalo; Cabello, Hernán; Fernández‐Bussy, Sebastián; Cabello, Francisca; Díaz, Juan
Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a very rare, recently described condition, characterised by fibrotic thickening of the pleural and subpleural parenchyma, predominantly in the upper lobes.1 Clinical manifestations and lung function tests are similar to those observed in restrictive interstitial pneumonias, and in some of the cases described, there was a history of recurrent infections, such as allergic bronchopulmonary aspergillosis or cystic fibrosis.2,3 Radiological findings include intense pleural thickening associated with signs of fibrosis, particularly in the upper lobes, with loss of volume and structural distortion, as observed in the case presented here.
A case report of a primary synovial chondromatosis of temporomandibular joint, producing medial displacement of the articular disc
(2014) Droguett, C.; Fumeaux, J.E.; Skármeta, N.P.
Synovial chondromatosis in the temporomandibular joint (TMJ) is a rare benign cartilaginous metaplasia characterized by the formation of loose bodies within the synovial joint space. This condition presents a specific triad of semiological characteristics featuring pain, swelling, and limitation of function. We will present a clinical case of a 49 years-old female patient who presented to the clinica Davila’s maxillofacial service with severe functional alterations in her right TMJ. Clinically, the patient had a maximum aperture of 15 mm wide, alteration of mandibular dynamics and preauricular pain. Posterior conducting a complete clinical examination and conclusive magnetic resonance imaging (MRI) findings it was decided to perform surgery on the joint. Articular cavity was exposed through a preauriclar approach, where the joint capsule presented no evident alteration. After opening the capsule, we were able to identify and extract multiple cartilaginous bodies both above and below the disc space. The articular surfaces were in good condition, while the articular disc was shifted to the medial portion of the cavity. The removal of the loose bodies was held the meniscopexy of the articular disc with a small joint anchor. The immediate post-operative period was uneventful, and the patient did not present any alteration with respect to motor function of facial expression. At the 6-week control, we recorded an increase in maximum mouth opening of 30 mm and a reduction of the pain. Six months later, we recorded an even wider mouth opening with no signs or evidence of recurrence
A case report of granuloma faciale, an uncommon cutaneous vasculitis
(2019) Arellano, Javier; Vargas, Pablo; Pulgar, Constanza; Neely, Gabriel; Corredoira, Yamile
Granuloma faciale is an uncommon benign dermatosis, with unknown etiology, usually asymptomatic, characterized by chronic inflammation localized in sun-exposed areas of the face with a characteristic histological pattern. Although response to treatment is variable, there are multiple therapeutic alternatives that have been reported to be effective in some patients, including systemic treatments with steroids and dapsone or also topical treatments like intralesional corticosteroid, cryotherapy and calcineurin inhibitors, such as tacrolimus. We present the case of an adult patient with an asymptomatic erythematous-violet plaque on the right cheek, with progressive slow growth over two years, clinically and histologically and pathologically compatible with a facial granuloma. The patient responded well to intralesional corticosteroids.
A case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer
(2021) Cordova-Delgado, Miguel; Bravo, María Loreto; Cumsille, Elisa; Hill, Charlotte N.; Muñoz-Medel, Matías; Pinto, Mauricio P.; Retamal, Ignacio N.; Lavanderos, María A.; Miquel, Juan Francisco; Rodriguez-Fernandez, Maria; Liao, Yuwei; Li, Zhiguang; Corvalán, Alejandro H.; Armisén, Ricardo; Garrido, Marcelo; Quiñones, Luis A.; Owen, Gareth I.
Background: Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.7%). No guidelines have been development for platinum. Herein, we present association between clinical factors and common SNPs in the development of grade 3–4 toxicity. Methods: Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in GSTP1, ERCC2, ERCC1, TP53, UMPS, SHMT1, MTHFR, ABCC2 and DPYD were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms. Results: Reported grade ≤ 2 and 3–4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected DPYD SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70–10.95, p = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19–1.08; p = 0.071). Combination of paired SNPs demonstrated significant associations in DPYD (rs1801265), UMPS (rs1801019), ABCC2 (rs717620) and SHMT1 (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs DPYD (rs1801265) + ABCC2 (rs717620), and DPYD (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity. Conclusion: Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.
A Chair-based Abbreviated Repositioning Maneuver (ChARM) for fast treatment of posterior BPPV
(2019) Michael, Pia; Muñoz, Daniel; Tuma, Anton; Gárate, Matías; Barraza, Cristian; Nuñez, Marcia; Breinbauer, Hayo
Purpose: To assess the effectiveness of a variation of the Epley maneuver, which we have titled "Chair-based Abbreviated Repositioning maneuver (ChARM)", in solving cases of benign positional paroxysmal vertigo (BPPV) of the posterior canal. ChARM addresses multiple issues of highly overloaded medical centers that delay its due and timely resolution. For example it does not necessitate an examination bed/table and requires only a backed chair, and less than 3 min to be performed. In combination with a recently published abbreviated diagnostic maneuver it can solve BPPV cases within few minutes of single medical visit. Methods: Patients being diagnosed with posterior BPPV by means of an abbreviated diagnostic maneuver were recruited. Immediately after diagnosis, a single attempt of ChARM was conducted. The patient was followed for 48 h and at 1 month after these procedures to assess the persistence of symptomatology. Results: 124 patients were treated with ChARM immediately after diagnosis during their very first medical visit. 92 patients (74.2%) solved their symptomatology completely after a single attempt of ChARM. The absence of symptoms persisted during the 30 days of follow-up. Discussion: ChARM showed high success rates in solving posterior BPPV. The entire diagnostic-treatment procedure takes less than 5 min to perform and may allow direct treatment of patients, thereby avoiding unnecessary referrals or full vestibular testing. These abbreviated tools may be particularly useful in primary care settings or heavily overloaded otolaryngology or neurology departments.
A changing etiologic scenario in liver transplantation for hepatocellular carcinoma in a multicenter cohort study from Latin America
(2018) Pinero, Federico; Costa, Paulo; Longatto Boteon, Yuri; Hoyos Duque, Sergio; Marciano, Sebastián; Anders, Margarita; Varóng, Adriana; Zerega, Alina; Poniachik, Jaime; Soza, Alejandro; Padilla Machaca, Martín; Menéndez, Josemaría; Zapata, Rodrigo; Vilatoba, Mario; Muñoz, Linda; Maraschio, Martín; Podestá, Luis G.; McCormack, Lucas; Gadano, Adrian; Boinc, Ilka S.F. Fatima; García, Parente; Silva, Marcelo; On behalf of the Latin American Liver Research, Education, Awareness Network (LALREAN)
Background and aim: Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC) and liver transplantation (LT). Our study focused on changing trendsof liver related HCC etiologies during the last years in Latin America. Methods: From a cohort of 2761 consecutive adult LT patients between 2005 and 2012 in 17 different centers, 435 with HCC were included. Different periods including years 2005—2006, 2007—2008, 2009—2010 and 2011—2012 were considered. Etiology of liver disease was confirmed in the explant. Results: Participating LT centers per country included 2 from Brazil (n = 191), 5 transplant programs from Argentina (n = 98), 2 from Colombia (n = 65), 4 from Chile (n = 49), 2 from Mexico (n = 12), and 1 from Peru (n = 11) and Uruguay (n = 9). Chronic hepatitis C infection was the leading cause of HCC in the overall cohort (37%), followed by HBV (25%) and alcoholic liver disease (17%). NAFLD and cryptogenic cirrhosis accounted for 6% and 7%, respectively. While HCV decreased from 48% in 2005—06 to 26% in 2011—12, NAFLD increased from 1.8% to 12.8% during the same period, accounting for the third cause of HCC. This represented a 6-fold increase in NAFLD-HCC, whereas HCV had a 2-fold decrease. Patients with NAFLD were older, had lower pre-LT serum AFP values and similar 5-year survival and recurrence rates than non-NAFLD. Conclusion: There might be a global changing figure regarding etiologies of HCC in Latin America. This epidemiological change on the incidence of HCC in the world, although it has been reported, should still be confirmed in prospective studies.
A Chilean Experience of Telestroke in a COVID-19 Pandemic Year
(2022) Delfino, Carlos; Mazzon, Enrico; Cavada, Gabriel; Muñoz Venturelli, Paula; Brunser, Alejandro; Jurado, Felipe; Lara, Lorena; Rocha, Diego; Arévalo, Mirya; Rojas, Diego; Mansilla, Eloy
Background and purpose: Telemedicine for stroke patients' care (telestroke [TS]) has grown notably in recent decades and may offer advantages during health crisis. Hospital admissions related to stroke have decreased globally during the COVID-19 pandemic, but scarce information is available regarding the effect of COVID-19 in TS. Using a population-based TS registry, we investigated the impact of the first year of the COVID-19 pandemic throughout our TS network in Santiago, Chile. Methods: Stroke codes evaluated after the onset of COVID-19 restrictions in Chile (defined as March 15, 2020) were compared with those evaluated in 2019. We analyzed differences between number of stroke codes, thrombolysis rate, stroke severity, and time from the stroke onset to hospital admission. Results: We observed that the number of stroke codes and the number of patients undergoing reperfusion therapy did not change significantly (p = 0.669 and 0.415, respectively). No differences were found with respect to the median time from the stroke onset to admission (p = 0.581) or in National Institutes of Health Stroke Scale (NIHSS) scores (p = 0.055). The decision-making-to-needle time was significantly shorter in the COVID-19 period (median 5 min [IQR 3-8], p < 0.016), but no significant changes were found at the other times. Conclusions: This study demonstrates the potential of adapting TS to extreme situations such as the COVID-19 pandemic, as well as the importance of establishing networks that facilitate patient access to quality treatments.
A comparative analysis of health status of international migrants and local population in Chile: a population-based, cross-sectional analysis from a social determinants of health perspective
(2022) Oyarte, Marcela; Cabieses, Báltica; Rada, Isabel
Background: During recent decades intraregional migration has increased in Latin America. Chile became one of the main receiving countries and hosted diverse international migrant groups. Evidence have suggested a healthy migrant effect (HME) on health status, but it remains scarce, controversial and needs to be updated. This study performed a comprehensive analysis verifying the existence of HME and its association with social determinants of health (SDH). Methods: We analyzed data from the Chilean National Socioeconomic Characterization Survey (CASEN, version 2017). Unadjusted prevalence of health status indicators such as negative self-perceived health, chronic morbidity, disability, and activity limitations were described in both international migrants and local population. Adjusted associations between these outcomes and sets of demographics, socioeconomic, access to healthcare, psychosocial and migration-related SDH were tested using multivariate logistic regression in each population. The HME for each health outcome was also tested using multivariate logistic regression and sequentially adjusting for each set of SDH (ref = Chilean). Results: International migrants had lower unadjusted prevalence of all health indicators compared to Chileans. That is, unadjusted analysis revealed an apparent HME in all health outcomes. Age, unemployment, and health care system affiliation were associated with health outcomes in both populations. Psychosocial determinants were both risk and protective for the analysed health outcomes. After adjustment for each set of SDH, the immigrant health advantage was only significant for chronic morbidity. Being migrant was associated with 39% lower odds of having chronic diseases compared to locals (OR: 0.61; 95% CI: 0.44-0.84; P = 0.0003). For all other outcomes, HME disappeared after adjusting by SDH, particularly unemployment, type of health system and psychosocial factors. Conclusions: Testing the HME in Chile revealed an advantage for chronic morbidities that remained significant after adjustment for SDH. This analysis shed light on health disparities between international migrants and local population in the Latin American region, with special relevance of unemployment, type of health system and psychosocial SDH. It also informed about differential exposures faced during migration process that could dissolve the HME over time. Evidence from this analytical approach is useful for informing health planning and intersectoral solutions from a SDH perspective.
A Comprehensive Analysis of the Effect of A>I(G) RNA-Editing Sites on Genotoxic Drug Response and Progression in Breast Cancer
(2024) Bernal, Yanara; Blanco, Alejandro; Sagredo, Eduardo; Oróstica, Karen; Alfaro, Ivan; Marcelain, Katherine; Armisén, Ricardo
Dysregulated A>I(G) RNA editing, which is mainly catalyzed by ADAR1 and is a type of post-transcriptional modification, has been linked to cancer. A low response to therapy in breast cancer (BC) is a significant contributor to mortality. However, it remains unclear if there is an association between A>I(G) RNA-edited sites and sensitivity to genotoxic drugs. To address this issue, we employed a stringent bioinformatics approach to identify differentially RNA-edited sites (DESs) associated with low or high sensitivity (FDR 0.1, log2 fold change 2.5) according to the IC50 of PARP inhibitors, anthracyclines, and alkylating agents using WGS/RNA-seq data in BC cell lines. We then validated these findings in patients with basal subtype BC. These DESs are mainly located in non-coding regions, but a lesser proportion in coding regions showed predicted deleterious consequences. Notably, some of these DESs are previously reported as oncogenic variants, and in genes related to DNA damage repair, drug metabolism, gene regulation, the cell cycle, and immune response. In patients with BC, we uncovered DESs predominantly in immune response genes, and a subset with a significant association (log-rank test p < 0.05) between RNA editing level in LSR, SMPDL3B, HTRA4, and LL22NC03-80A10.6 genes, and progression-free survival. Our findings provide a landscape of RNA-edited sites that may be involved in drug response mechanisms, highlighting the value of A>I(G) RNA editing in clinical outcomes for BC.
A core outcome set for trials in miscarriage management and prevention: An international consensus development study
(2023) Dhillon-Smith, Rima K.; Melo, Pedro; Devall, Adam James; Smith, Paul Philip; Al-Memar, Maya; Barnhart, Kurt; Condous, George; Christiansen, Ole Bjarne; Goddijn, Mariëtte; Jurkovic, Davor; Lissauer, David; Maheshwari, Abha; Oladapo, Olufemi
Objective: To develop core outcome sets (COS) for miscarriage management and prevention. Design: Modified Delphi survey combined with a consensus development meeting. Setting: International. Population: Stakeholder groups included healthcare providers, international experts, researchers, charities and couples with lived experience of miscarriage from 15 countries: 129 stakeholders for miscarriage management and 437 for miscarriage prevention. Methods: Modified Delphi method and modified nominal group technique. Results: The final COS for miscarriage management comprises six outcomes: efficacy of treatment, heavy vaginal bleeding, pelvic infection, maternal death, treatment or procedure-related complications, and patient satisfaction. The final COS for miscarriage prevention comprises 12 outcomes: pregnancy loss <24 weeks' gestation, live birth, gestation at birth, pre-term birth, congenital abnormalities, fetal growth restriction, maternal (antenatal) complications, compliance with intervention, patient satisfaction, maternal hospitalisation, neonatal or infant hospitalisation, and neonatal or infant death. Other outcomes identified as important were mental health-related outcomes, future fertility and health economic outcomes. Conclusions: This study has developed two core outcome sets, through robust methodology, that should be implemented across future randomised trials and systematic reviews in miscarriage management and prevention. This work will help to standardise outcome selection, collection and reporting, and improve the quality and safety of future studies in miscarriage.
A description of Chilean food and nutrition health policies
(2021) Rodríguez-Osiac, Lorena; Pinheiro Fernandes, Anna; Mujica-Coopman, María; Caro-Moya, Patricia; Navarro-Rosenblatt, Deborah;
Background: Chile has implemented numerous successful food and nutrition initiatives since the early 20th century, aiming to address malnutritionin all its forms. Aim: To summarize the major nutrition and food-related policies, strategies, and programs implemented in Chile, using the NOURISHING Framework. Material and Methods: The NOURISHING framework proposes a methodology for reporting, monitoring, and categorizing actions to promote healthier eating in three main domains: food environment, food system and behavior change communication. The data collection was carried out reviewing the databases of the Chilean Ministries of Health, Education and Social Development, and the Parliament. Information about nutrition related public health policies, strategies or programs was obtained from peer reviewed articles, official reports, official State websites, as well as interviews with former and current stakeholders. Results: Chile has mandatory nutritional labeling that was updated to front-of-package warning labels about critical nutrients. In addition, the advertising of unhealthy foods and breast milk substitutes is restricted, among other food and nutrition policies. Nevertheless, strategies related to mass and social media communication campaigns, or periodic education and information interventions still need to be implemented. Conclusions: Using the NOURISHING framework, a comprehensive summary and description of nutrition and food public health policies implemented in Chile is described. An overview of the policy changes required according to the nutritional transition in Chile is provided.
A dual mechanism fully blocks ethanol relapse: Role of vagal innervation
(2022) Quintanilla, María; Ezquer, Fernando; Morales, Paola; Santapau, Daniela; Ezquer, Marcelo; Herrera, Mario; Israel, Yedy
Previous studies showed that vagotomy markedly inhibits alcohol self-administration. Present studies hypothesised that vagotomy significantly adds to the inhibition of alcohol relapse induced by drugs that reduce the alcohol-induced hyperglutamatergic state (e.g., N-acetylcysteine + acetylsalicylic acid). The alcohol relapse paradigm tested gauges the elevated alcohol intake observed in animals that had consumed ethanol chronically, were subjected to a prolonged alcohol deprivation and are subsequently allowed ethanol re-access. Ethanol-drinker rats (UChB) were exposed to 10% and 20% ethanol and water concurrently for 4 months, were alcohol deprived for 14 days and were thereafter allowed re-access to the ethanol solutions. An initial binge-like drinking episode is observed upon ethanol re-access, followed by a protracted elevated ethanol intake that exceeds the predeprivation intake baseline. Prior to ethanol re-access, animals were (i) administered N-acetylcysteine (40 mg/kg/day) + acetylsalicylic acid (15 mg/kg/day), (ii) were bilaterally vagotomised, (iii) were exposed to both treatments or (iv) received no treatments. The initial binge-like relapse intake and a protracted elevated ethanol intake observed after repeated ethanol deprivations/re-access cycles were inhibited by 50%-70% by the administration of N-acetylcysteine + acetylsalicylic acid and by 40%-70% by vagotomy, while the combined vagotomy plus N-acetylcysteine + acetylsalicylic acid treatment inhibited both the initial binge-like intake and the protracted ethanol intake by >95% (p < 0.001), disclosing a dual mechanism of ethanol relapse and subsequent inhibition beyond that induced by either treatment alone. Future exploration into the mechanism by which vagal activity contributes to ethanol relapse may have translational promise.

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