Artículos Medicina y Ciencias de la Salud

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Chromosome-Mediated Colistin Resistance in Clinical Isolates of Klebsiella pneumoniae and Escherichia coli: Mutation Analysis in the Light of Genetic Background
(2023) Riquelme, María; Martinez, Rodrigo; Brito, Bárbara; García, Patricia; Legarraga, Paulette; Wozniak, Aniela
Purpose: Colistin resistance mechanisms involving mutations in chromosomal genes associated with LPS modification are not completely understood. Mutations in genes coding for the MgrB regulator frequently account for colistin resistance in Klebsiella pneumoniae, whereas mutations in genes coding for PhoPQ and PmrAB are frequent in E. coli. Our aim was to perform a genetic analysis of chromosomal mutations in colistin-resistant (MIC ≥4 µg/mL) clinical isolates of K. pneumoniae (n = 8) and E. coli (n = 7) of different STs. Methods: Isolates were obtained in a 3-year period in a university hospital in Santiago, Chile. Susceptibility to colistin, aminoglycosides, cephalosporins, carbapenems and ciprofloxacin was determined through broth microdilution. Whole genome sequencing was performed for all isolates and chromosomal gene sequences were compared with sequences of colistin-susceptible isolates of the same sequence types. Results: None of the isolates carried mcr genes. Most of the isolates were susceptible to all the antibiotics analyzed. E. coli isolates were ST69, ST127, ST59, ST131 and ST14, and K. pneumoniae isolates were ST454, ST45, ST6293, ST380 and ST25. All the isolates had mutations in chromosomal genes analyzed. K. pneumoniae had mutations mainly in mgrB gene, whereas E. coli had mutations in pmrA, pmrB and pmrE genes. Most of the amino acid changes in LPS-modifying enzymes of colistin-resistant isolates were found in colistin-susceptible isolates of the same and/or different ST. Eleven of them were found only in colistin-resistant isolates. Conclusion: Colistin resistance mechanisms depend on genetic background, and are due to chromosomal mutations, which implies a lower risk of transmission than plasmid-mediated genes. Colistin resistance is not associated with multidrug-resistance, nor to high-risk sequence types.
Changes in tobacco imagery and smokers' depiction in Spanish top-grossing films before and after the implementation of a comprehensive tobacco control policy in Spain
(2023) Feliu, Ariadna; Quintero, Alex; Peruga, Armando; Carnicer, Dolors; Antón, Laura; Rey, Juan; Fernández, Esteve
Introduction: As more restrictions on tobacco marketing communication are implemented, tobacco marketing has persisted through smoking in films. Our aims were to assess changes in tobacco imagery exposure in Spanish top-grossing films before and after the banning of tobacco advertising in Spain, and to determine whether the depiction of smoking characters has changed over the years. Methods: A repeated cross-sectional study measured the tobacco content in the 10 Spanish top-grossing films in 2005, 2010 and 2015 (n=30) before and after a complete tobacco advertising ban. We conducted a descriptive and regression analysis of changes in tobacco impressions by year. Results: The 30 films contained 1378 tobacco occurrences (90.2% positive for tobacco) with a median length of eight seconds onscreen. Total tobacco occurrences deemed positive for tobacco interests significantly increased in 2010 and 2015 compared to 2005. However, we observed decreased odds of tobacco brands appearances (OR=0.25; p<0.001) in 2010 and of implied tobacco use (OR=0.44; p=0.002), and tobacco brands appearances (OR=0.36; p<0.001) in 2015 compared to 2005. There was a change of pattern in the type of role smokers played from a leading role to a supporting one (p<0.001). The population reach of positive for tobacco occurrence in Spanish top-grossing films decreased from 15.9 (95% CI: 15.86-15.86) per 1000 spectators in 2005 to 0.8 (95% CI: 0.82-0.82) in 2015. Conclusions: The implementation of a ban on complete tobacco product advertising was followed by a decrease in tobacco incidents across top-grossing Spanish films. Yet, exposure to smoking in films is still unacceptably high.
Antibiotic Consumption During the Coronavirus Disease 2019 Pandemic and Emergence of Carbapenemase-Producing Klebsiella pneumoniae Lineages Among Inpatients in a Chilean Hospital: A Time-Series Study and Phylogenomic Analysis
(2023) Allel, Kasim; Peters, Anne Sophie; Conejeros, José; Martínez, José; Spencer, Maria; Riquelme, Roberto; Rivas Jiménez, Lina María; Rojas, Pamela; Orellana, Cristian; García, Patricia; Araos Bralic, Rafael Ignacio; McGovern, Olivia; Patel, Twisha; Arias, Cesar; Lessa, Fernanda; Undurraga, Eduardo; Munita, Jose M.
Background: The impact of coronavirus disease 2019 (COVID-19) on antimicrobial use (AU) and resistance has not been well evaluated in South America. These data are critical to inform national policies and clinical care. Methods: At a tertiary hospital in Santiago, Chile, between 2018 and 2022, subdivided into pre- (3/2018-2/2020) and post-COVID-19 onset (3/2020-2/2022), we evaluated intravenous AU and frequency of carbapenem-resistant Enterobacterales (CRE). We grouped monthly AU (defined daily doses [DDD]/1000 patient-days) into broad-spectrum β-lactams, carbapenems, and colistin and used interrupted time-series analysis to compare AU during pre- and post-pandemic onset. We studied the frequency of carbapenemase-producing (CP) CRE and performed whole-genome sequencing analyses of all carbapenem-resistant (CR) Klebsiella pneumoniae (CRKpn) isolates collected during the study period. Results: Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P < .001), 50.9 to 110.1 (P < .001), and 4.1 to 13.3 (P < .001) for broad-spectrum β-lactams, carbapenems, and colistin, respectively. The frequency of CP-CRE increased from 12.8% pre-COVID-19 to 51.9% after pandemic onset (P < .001). The most frequent CRE species in both periods was CRKpn (79.5% and 76.5%, respectively). The expansion of CP-CRE harboring blaNDM was particularly noticeable, increasing from 40% (n = 4/10) before to 73.6% (n = 39/53) after pandemic onset (P < .001). Our phylogenomic analyses revealed the emergence of two distinct genomic lineages of CP-CRKpn: ST45, harboring blaNDM, and ST1161, which carried blaKPC. Conclusions: AU and the frequency of CP-CRE increased after COVID-19 onset. The increase in CP-CRKpn was driven by the emergence of novel genomic lineages. Our observations highlight the need to strengthen infection prevention and control and antimicrobial stewardship efforts.
Annona cherimola Seed Extracts Trigger an Early Apoptosis Response and Selective Anticlonogenic Activity against the Human Gastric Carcinoma Cell Line SNU-1
(2023) Macuer, Johan; Giovagnoli, Claudia; Bernal, Giuliano; Lobos, Lorena; De la Fuente, Erwin; Araya, Michael; Ibáñez, Cristian
The aim of this study was to evaluate, for the first time, the antiproliferative, apoptotic and diminishing effects of the anchored growth-independent capacity of an ethanol macerate extract from the Annona cherimola seed (EMCHS) in the human gastric cancer cell line SNU-1. The cells treated with EMCHS (20 μg/mL) significantly reduced the capacity to form clones of the tumor cell. Moreover, 50 μg/mL of EMCHS extract induced apoptosis, as was shown by the Annexin-V assay. UHPLC-MS/MS analysis detected two acetogenins (Annonacinone and Annonacin) in the EMCHS, which could be largely responsible for its selective antiproliferative effect. The identification of fatty acids by GC-FID showed the presence of eight fatty acids, among which was, oleic acid, which has recognized activity as an adjuvant in antitumor treatments. Taken together, our results indicate that the EMCHS seems promising for use as a natural therapy against gastric cancer disease.
Squamous Cell CarcinomaDeveloped in a TrichilemmalCyst, an Incidental Finding
(2023) Perez-Wilson, Jaime; Coulon, Gabriela; Whittle, Carolina; Castro-Avila, Ana Cristina
A 61-year-old man with no previous cancer history attended the dermatology clinic with a three-year history of asymptomatic swelling on the posterior aspect of the left elbow. Physical examination revealed a subcutaneous nodule of 1cm in diameter, with no epidermal changes. A Doppler ultrasound was requested, which revealed a predominantly dermal hypodermal cystic lesion with hypoechogenic content, an echogenic rim and small echogenic foci compatible with an epidermal cyst, no solid inner nodule was depicted (Fig. 1). An excisional biopsy was performed, which revealed a trichilemmal-type follicular cyst with a 0.5mm thickness well-differentiated squamous cell carcinoma (SCC) in its wall (Fig. 2). It was presented to the oncology committee that suggested local extent of 1cm The new biopsy did not show signs of residual neoplasia. At six months of follow-up, the patient did not present clinical or dermoscopic signs of recurrence.
Administration of Secretome Derived from Human Mesenchymal Stem Cells Induces Hepatoprotective Effects in Models of Idiosyncratic Drug-Induced Liver Injury Caused by Amiodarone or Tamoxifen
(2023) Huang, Ya-Lin; De Gregorio, Cristian; Silva, Verónica; Elorza, Álvaro; Léniz, Patricio; Aliaga, Víctor; Maracaja, Vinicius; Budini, Mauricio; Ezquer, Fernando; Ezquer, Marcelo
Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. While many factors may contribute to the susceptibility to DILI, obese patients with hepatic steatosis are particularly prone to suffer DILI. The secretome derived from mesenchymal stem cell has been shown to have hepatoprotective effects in diverse in vitro and in vivo models. In this study, we evaluate whether MSC secretome could improve DILI mediated by amiodarone (AMI) or tamoxifen (TMX). Hepatic HepG2 and HepaRG cells were incubated with AMI or TMX, alone or with the secretome of MSCs obtained from human adipose tissue. These studies demonstrate that coincubation of AMI or TMX with MSC secretome increases cell viability, prevents the activation of apoptosis pathways, and stimulates the expression of priming phase genes, leading to higher proliferation rates. As proof of concept, in a C57BL/6 mouse model of hepatic steatosis and chronic exposure to AMI, the MSC secretome was administered endovenously. In this study, liver injury was significantly attenuated, with a decrease in cell infiltration and stimulation of the regenerative response. The present results indicate that MSC secretome administration has the potential to be an adjunctive cell-free therapy to prevent liver failure derived from DILI caused by TMX or AMI.
A Third Dose of SARS-CoV-2 mRNA Vaccine Improves Immune Response in Chronic Kidney Disease Patients
(2023) Poli Harlowe, María Cecilia; Vial Cox, María Cecilia; Rey, Emma; González, Natalia; Cortés, Lina; Hormazabal, Juan; Ramírez, Carolina; De la Cruz, Javiera; Ulloa, Camilo
Chronic kidney disease (CKD) patients have an increased risk of morbidity and mortality following SARS-CoV-2 infection. Vaccination in these patients is prioritized, and monitoring of the immune response is paramount to define further vaccination strategies. This prospective study included a cohort of 100 adult CKD patients: 48 with kidney transplant (KT) and 52 on hemodialysis without prior COVID-19. The patients were assessed for humoral and cellular immune responses after four months of an anti-SARS-CoV-2 primary two-dose vaccination scheme (CoronaVac or BNT162b2) and one month after a booster third dose of BNT162b2 vaccine. We identified poor cellular and humoral immune responses in the CKD patients after a primary vaccination scheme, and these responses were improved by a booster. Robust polyfunctional CD4+ T cell responses were observed in the KT patients after a booster, and this could be attributed to a higher proportion of the patients having been vaccinated with homologous BNT162b2 schemes. However, even after the booster, the KT patients exhibited lower neutralizing antibodies, attributable to specific immunosuppressive treatments. Four patients suffered severe COVID-19 despite three-dose vaccination, and all had low polyfunctional T-cell responses, underscoring the importance of this functional subset in viral protection. In conclusion, a booster dose of SARS-CoV-2 mRNA vaccine in CKD patients improves the impaired humoral and cellular immune responses observed after a primary vaccination scheme.
A Novel Gemcitabine-Resistant Gallbladder Cancer Model Provides Insights into Molecular Changes Occurring during Acquired Resistance
(2023) Vergara, Luis; Bizama, Carolina; Zhong, Jun; Buchegger, Kurt; Suárez, Felipe; Rosa, Lorena; Ili, Carmen; Weber, Helga; Obreque, Javiera; Espinoza, Karena; Repetto, Gabriela; Roa, Juan; Leal, Pamela; García, Patricia
Treatment options for advanced gallbladder cancer (GBC) are scarce and usually rely on cytotoxic chemotherapy, but the effectiveness of any regimen is limited and recurrence rates are high. Here, we investigated the molecular mechanisms of acquired resistance in GBC through the development and characterization of two gemcitabine-resistant GBC cell sublines (NOZ GemR and TGBC1 GemR). Morphological changes, cross-resistance, and migratory/invasive capabilities were evaluated. Then, microarray-based transcriptome profiling and quantitative SILAC-based phosphotyrosine proteomic analyses were performed to identify biological processes and signaling pathways dysregulated in gemcitabine-resistant GBC cells. The transcriptome profiling of parental and gemcitabine-resistant cells revealed the dysregulation of protein-coding genes that promote the enrichment of biological processes such as epithelial-to-mesenchymal transition and drug metabolism. On the other hand, the phosphoproteomics analysis of NOZ GemR identified aberrantly dysregulated signaling pathways in resistant cells as well as active kinases, such as ABL1, PDGFRA, and LYN, which could be novel therapeutic targets in GBC. Accordingly, NOZ GemR showed increased sensitivity toward the multikinase inhibitor dasatinib compared to parental cells. Our study describes transcriptome changes and altered signaling pathways occurring in gemcitabine-resistant GBC cells, which greatly expands our understanding of the underlying mechanisms of acquired drug resistance in GBC.
Reliability and acceptability of web-based administration of Spanish ages and stages questionnaires third edition
(2023) Schonhaut , Luisa; Armijo, Ivan; Rojas, Paula; Cabrera, Leonardo; Boisier, Roberto
To analyse the reliability of 6 age intervals of Spanishweb-based Ages and Stages Questionnaires Third Edition(WB-ASQ-3) and parents' acceptability, in a clinical practicecontext, during COVID-19 pandemic and lockdown in Chile.Cross-sectional study with a longitudinal component. Inter-nal consistency was analysed by Cronbach's alpha and Pear-son product–moment correlation, Pearson's correlationsbetween intervals questionnaires were analysed. Accept-ability was determined using a parental satisfaction survey.1061 children completed 2318 validated questionnaires.Scores were compared with normative sample, except forGross motor at 8 and 12 months, and Communication at12, 18 and 24 months, without differences to the previousChileans sample. In domain analysis, Cronbach's alpharanged from 0.36 to 0.80 and reached 0.74 to 0.81 for theoverall test. Strong positive correlation between the domainand overall score was obtained. Correlation between mostquestionnaires at different ages was positive and significant.Parental surveys show high satisfaction; parents werethankful for being able to monitor children's development.WB-ASQ-3 is a reliable and feasible screening system, par-ticularly when the test is taken as a whole, rather than by domains. It is remarkably high acceptability among parents,especially in complex times such as the lockdown and theCOVID-19 pandemic.
Whole-genome sequencing reveals changes in genomic diversity and distinctive repertoires of T3SS and T6SS effector candidates in Chilean clinical Campylobacter strains
(2023) Katz, Assaf; Porte, Lorena; Weitzel, Thomas; Varela, Carmen; Muñoz, Cristina; Ugalde, Juan; Grim, Christopher; González, Narjol; Blondel, Carlos; Bravo, Verónica
Campylobacter is the leading cause of bacterial gastroenteritis worldwide and an emerging and neglected pathogen in South America. This zoonotic pathogen colonizes the gastrointestinal tract of a wide range of mammals and birds, with poultry as the most important reservoir for human infections. Apart from its high morbidity rates, the emergence of resistant strains is of global concern. The aims of this work were to determine genetic diversity, presence of antimicrobial resistance determinants and virulence potential of Campylobacter spp. isolated from patients with acute gastrointestinal disease at 'Clinica Alemana', Santiago de Chile. The study considered the isolation of Campylobacter spp., from stool samples during a 20-month period (January 2020 to September 2021). We sequenced (NextSeq, Illumina) and performed an in-depth analysis of the genome sequences of 88 Campylobacter jejuni and 2 Campylobacter coli strains isolated from clinical samples in Chile. We identified a high genetic diversity among C. jejuni strains and the emergence of prevalent clonal complexes, which were not identified in our previous reports. While ~40% of strains harbored a mutation in the gyrA gene associated with fluoroquinolone resistance, no macrolide-resistance determinants were detected. Interestingly, gene clusters encoding virulence factors such as the T6SS or genes associated with long-term sequelae such as Guillain-Barré syndrome showed lineage-relatedness. In addition, our analysis revealed a high degree of variability regarding the presence of fT3SS and T6SS effector proteins in comparison to type strains 81-176, F38011, and NCTC 11168 and 488. Our study provides important insights into the molecular epidemiology of this emerging foodborne pathogen. In addition, the differences observed regarding the repertoire of fT3SS and T6SS effector proteins could have an impact on the pathogenic potential and transmissibility of these Latin American isolates, posing another challenge in characterizing the infection dynamics of this emergent and neglected bacterial pathogen.
Maintenance of chronicity signatures in fibroblasts isolated from recessive dystrophic epidermolysis bullosa chronic wound dressings under culture conditions
(2023) De Gregorio, Cristian; Catalán, Evelyng; Garrido, Gabriel; Morandé, Pilar; Castillo, Jimena; Muñoz, Catalina; Cofré, Glenda; Huang, Ya-Lin; Cuadra, Bárbara; Murgas, Paola; Calvo, Margarita; Altermatt, Fernando; Joao, María; Palisson, Francis; South, Andrew; Ezquer, Marcelo; Ezquer, Marcelo; Fuentes, Ignacia
Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the COL7A1 gene, coding for type VII collagen (C7), an important component of anchoring fibrils in the basement membrane of the epidermis. RDEB patients suffer from skin fragility starting with blister formation and evolving into chronic wounds, inflammation and skin fibrosis, with a high risk of developing aggressive skin carcinomas. Restricted therapeutic options are limited by the lack of in vitro models of defective wound healing in RDEB patients. Results: In order to explore a more efficient, non-invasive in vitro model for RDEB studies, we obtained patient fibroblasts derived from discarded dressings) and examined their phenotypic features compared with fibroblasts derived from non-injured skin of RDEB and healthy-donor skin biopsies. Our results demonstrate that fibroblasts derived from RDEB chronic wounds (RDEB-CW) displayed characteristics of senescent cells, increased myofibroblast differentiation, and augmented levels of TGF-β1 signaling components compared to fibroblasts derived from RDEB acute wounds and unaffected RDEB skin as well as skin from healthy-donors. Furthermore, RDEB-CW fibroblasts exhibited an increased pattern of inflammatory cytokine secretion (IL-1β and IL-6) when compared with RDEB and control fibroblasts. Interestingly, these aberrant patterns were found specifically in RDEB-CW fibroblasts independent of the culturing method, since fibroblasts obtained from dressing of acute wounds displayed a phenotype more similar to fibroblasts obtained from RDEB normal skin biopsies. Conclusions: Our results show that in vitro cultured RDEB-CW fibroblasts maintain distinctive cellular and molecular characteristics resembling the inflammatory and fibrotic microenvironment observed in RDEB patients’ chronic wounds. This work describes a novel, non-invasive and painless strategy to obtain human fibroblasts chronically subjected to an inflammatory and fibrotic environment, supporting their use as an accessible model for in vitro studies of RDEB wound healing pathogenesis. As such, this approach is well suited to testing new therapeutic strategies under controlled laboratory conditions.
Successful eradication rate of Helicobacter pylori with empirical antibiotic treatment in pediatric patients from a Tertiary Hospital
(2023) Darritchon Lama, Sofía; Díaz García, Diego; Toledo Complido, Marcela; Lucero, Yalda
Helicobacter pylori infection is a common condition that, in the long term, is associated with the development of peptic ulcer disease and eventually gastric cancer, which could be prevented with timely treatment. Optimally, eradication success should be greater than 90%, but the recommended empirical reatments do not achieve these rates in real-life conditions. Objective: To determine the success rate of first-line empirical eradication treatment against H. pylori in pediatric patients treated in a tertiary hospital. Patients and Method: Retrospective descriptive study in patients with H. pylori infection detected in gastric biopsies and who had received first-line antibiotic treatment during the period 2017-2021. A negative result of an antigen test in stools or new iopsies after ≥ 1 month after
Infecciones por helmintos intestinales en Chile: Análisis retrospectivo en Santiago, años 2015-2019
(2023) Ahumada, María; Haecker, Felipe; Porte, Lorena; Weitzel, Thomas
Introducción: Existe escasa evidencia epidemiológica actual sobre helmintos intestinales en Chile. Objetivo: Describir la prevalencia de infecciones por helmintos intestinales en un centro de salud en Santiago, Chile. Métodos: Análisis retrospectivo de helmintos intestinales diagnosticados en muestras parasitológicas de rutina en el Laboratorio de Microbiología de Clínica Alemana de Santiago, entre los años 2015 y 2019. Las pruebas diagnósticas se seleccionaron según la solicitud médica. Los datos se obtuvieron de los sistemas informáticos del laboratorio y se analizaron de manera anonimizada. Resultados: Se detectaron 127 infecciones por helmintos en 11.809 muestras estudiadas (1,1%). Estas infecciones fueron: 78 (61,4%) Enterobius vermicularis, 25 (19,6%) Dibothriocephalus/Adenocephalus spp., 9 (7,1%) Taenia spp., 6 (4,7%) Pseudoterranova spp., 5 (3,9%) Strongyloides stercoralis y 4 (3,1%) Ascaris lumbricoides. Enterobius vermicularis predominó en niños y adolescentes; Dibothriocephalus/ Adenocephalus spp. predominó en adultos. Conclusión: El estudio proporciona información epidemiológica actual sobre la distribución de helmintos intestinales en muestras clínicas en Santiago, Chile. Enterobius vermicularis fue prevalente, seguido de helmintos transmitidos por alimentos mientras que los transmitidos por el suelo solo se detectaron ocasionalmente. El surgimiento de difilobotriasis y anisakidosis (pseudoterranoviasis), es relevante y posiblemente se relacione con cambios en las condiciones de vida y la cultura alimentaria en Chile. Background: Epidemiological information on the current prevalence of intestinal helminths in Chile is scarce. Aim: To describe the prevalence of different intestinal helminth infections in a healthcare center in Santiago, Chile. Methods: We performed a retrospective analysis of intestinal helminths diagnosed in routine parasitological samples in the microbiological laboratory of Clínica Alemana Santiago, Chile, between 2015 and 2019. Diagnostic tests were applied according to the sender's request. Data were obtained from laboratory information systems and analyzed in an anonymized manner. Results: Among 11,809 samples, 127 (1.1%) helminth infections were detected, of those, 78 (61.4%) were Enterobius vermicularis, 25 (19.6%) Dibothriocephalus/Adenocephalus spp., 9 (7.1%) Taenia spp., 6 (4.7%) Pseudoterranova spp., 5 (3.9%) Strongyloides stercoralis, and 4 (3.1%) Ascaris lumbricoides. Enterobius vermicularis was predominant among children and adolescents, while Dibothriocephalus/Adenocephalus spp. was the most frequent helminth in adults. Conclusion: The study provides updated epidemiological information on distribution of helminth infections in clinical samples in Santiago, Chile. After E. vermicularis, food-borne helminths were second most prevalent, while soiltransmitted helminths were very rarely detected. The emergence of diphyllobothriasis and anisakidosis (pseudoterranoviasis) is noteworthy and possibly related to changes in living conditions and food culture in Chile.
Nanoscopic Distal Biceps Repair With Cortical Button and Interference Screw
(2023) Reinares, Felipe; De la Maza, Francisca; De la Paz; Joaquin; Angulo, Manuela; Lecaros, Juan; Ruiz, Francisco
Distal biceps pathology can be addressed using different techniques, each with its advantages and disadvantages. The current trend is to move toward minimally invasive procedures based on feasibility and known clinical benefits. Endoscopy for distal biceps pathology is a safe procedure. Through the NanoScope, this procedure is even more effective and safer.
Visual-spatial processing impairment in the occipital-frontal connectivity network at early stages of Alzheimer's disease
(2023) Plaza, Iván; Brunetti, Enzo; Montefusco, Rodrigo; Madariaga, Samuel; Hafelin, Rodrigo; Madariaga, Samuel; Ponce, Daniela; Behrens, María; Maldonado, Pedro; Lima, Andrea
Introduction: Alzheimer's disease (AD) is the leading cause of dementia worldwide, but its pathophysiological phenomena are not fully elucidated. Many neurophysiological markers have been suggested to identify early cognitive impairments of AD. However, the diagnosis of this disease remains a challenge for specialists. In the present cross-sectional study, our objective was to evaluate the manifestations and mechanisms underlying visual-spatial deficits at the early stages of AD. Methods: We combined behavioral, electroencephalography (EEG), and eye movement recordings during the performance of a spatial navigation task (a virtual version of the Morris Water Maze adapted to humans). Participants (69-88 years old) with amnesic mild cognitive impairment-Clinical Dementia Rating scale (aMCI-CDR 0.5) were selected as probable early AD (eAD) by a neurologist specialized in dementia. All patients included in this study were evaluated at the CDR 0.5 stage but progressed to probable AD during clinical follow-up. An equal number of matching healthy controls (HCs) were evaluated while performing the navigation task. Data were collected at the Department of Neurology of the Clinical Hospital of the Universidad de Chile and the Department of Neuroscience of the Faculty of Universidad de Chile. Results: Participants with aMCI preceding AD (eAD) showed impaired spatial learning and their visual exploration differed from the control group. eAD group did not clearly prefer regions of interest that could guide solving the task, while controls did. The eAD group showed decreased visual occipital evoked potentials associated with eye fixations, recorded at occipital electrodes. They also showed an alteration of the spatial spread of activity to parietal and frontal regions at the end of the task. The control group presented marked occipital activity in the beta band (15-20 Hz) at early visual processing time. The eAD group showed a reduction in beta band functional connectivity in the prefrontal cortices reflecting poor planning of navigation strategies. Discussion: We found that EEG signals combined with visual-spatial navigation analysis, yielded early and specific features that may underlie the basis for understanding the loss of functional connectivity in AD. Still, our results are clinically promising for early diagnosis required to improve quality of life and decrease healthcare costs.
Campylobacter spp. Prevalence in Santiago, Chile: A Study Based on Molecular Detection in Clinical Stool Samples from 2014 to 2019
(2023) Porte, Lorena; Pérez, Caricia; Barbé, Mario; Varela, Carmen; Vollrath, Valeska; Legarraga, Paulette; Weitzel, Thomas
Campylobacter spp. is an emerging cause of infectious diarrhea worldwide. In South American countries such as Chile, its prevalence is underestimated due to inadequate detection methods. Gastrointestinal multiplex PCR panels (GMP) permit rapid and sensitive detection of bacterial pathogens and provide important epidemiological information. This study aimed to analyze Campylobacter epidemiology using the results of molecular methods and to compare molecular detection results to those of culture methods. We performed a retrospective, descriptive analysis of Campylobacter spp. detected in clinical stool samples between 2014-2019 by GMP and culture. Within 16,582 specimens examined by GMP, Campylobacter was the most prevalent enteropathogenic bacteria (8.5%), followed by Salmonella spp. (3.9%), Shigella spp./enteroinvasive Escherichia coli (EIEC) (1.9%), and Yersinia enterocolitica (0.8%). The highest Campylobacter prevalence occurred in 2014/2015. Campylobacteriosis affected more males (57.2%) and adults from 19-65 years (47.9%) and showed a bimodal seasonality with summer and winter peaks. In 11,251 routine stool cultures, Campylobacter spp. was detected in 4.6%, mostly C. jejuni (89.6%). Among 4533 samples tested by GMP and culture in parallel, GMP showed a superior sensitivity (99.1% versus 50%, respectively). The study suggests that Campylobacter spp. is the most frequent bacterial enteropathogen in Chile.
Who is in the emergency room matters when we talk about door-to-needle time: a single-center experience [Quien está en el servicio de emergencia importa al hablar de tiempo puerta-aguja: experiencia de un centro clínico]
(2023) brunser, alejandro; Nuñez; Juan; Mansilla, Eloy; Cavada, Gabriel; Olavarría, Verónica V.; Munoz Venturelli, Paula; Lavados, Pablo
Background: The efficacy of intravenous thrombolysis (IVT) is time-dependent. Objective: To compare the door-to-needle (DTN) time of stroke neurologists (SNs) versus non-stroke neurologists (NSNs) and emergency room physicians (EPs). Additionally, we aimed to determine elements associated with DTN ≤ 20 minutes. Methods: Prospective study of patients with IVT treated at Clínica Alemana between June 2016 and September 2021. Results: A total of 301 patients underwent treatment for IVT. The mean DTN time was 43.3 ± 23.6 minutes. One hundred seventy-three (57.4%) patients were evaluated by SNs, 122 (40.5%) by NSNs, and 6 (2.1%) by EPs. The mean DTN times were 40.8 ± 23, 46 ± 24.7, and 58 ± 22.5 minutes, respectively. Door-to-needle time ≤ 20 minutes occurred more frequently when patients were treated by SNs compared to NSNs and EPs: 15%, 4%, and 0%, respectively (odds ratio [OR]: 4.3, 95% confidence interval [95%CI]: 1.66–11.5, p = 0.004). In univariate analysis DTN time ≤ 20 minutes was associated with treatment by a SN ( p = 0.002), coronavirus disease 2019 pandemic period ( p = 0.21), time to emergency room (ER) ( p = 0.21), presence of diabetes ( p = 0.142), hypercholesterolemia ( p = 0.007), atrial fibrillation ( p < 0.09), score on the National Institutes of Health Stroke Scale (NIHSS) ( p = 0.001), lower systolic ( p = 0.143) and diastolic ( p = 0.21) blood pressures, the Alberta Stroke Program Early CT Score (ASPECTS; p = 0.09), vessel occlusion ( p = 0.05), use of tenecteplase ( p = 0.18), thrombectomy ( p = 0.13), and years of experience of the physician ( p < 0.001). After multivariate analysis, being treated by a SN (OR: 3.95; 95%CI: 1.44–10.8; p = 0.007), NIHSS (OR: 1.07; 95%CI: 1.02–1.12; p < 0.002) and lower systolic blood pressure (OR: 0.98; 95%CI: 0.96–0.99; p < 0.003) remained significant. Conclusion: Treatment by a SN resulted in a higher probability of treating the patient in a DTN time within 20 minutes.
Neumoencéfalo, una revisión de literatura
(2023) Gomez, Jaime; Rojas, David; Melo, Rómulo; Rivera, Belen; Rojas, Francisca
El neumoencéfalo corresponde a la presencia de aire intracraneal y, en general, es asintomático y autolimitado. Puede ocurrir posterior a trauma, cirugía craneofacial, defectos congénitos, infección, neoplasia o de forma espontánea. El neumoencéfalo a tensión es una emergencia neuroquirúrgica, en la que se acumula aire intracraneal de forma continua que genera un efecto de masa. Clínicamente, se caracteriza por cefalea y un deterioro neurológico marcado. A pesar de ser poco frecuente, es relevante considerar el neumoencéfalo a tensión como una posible complicación en pacientes con antecedente de neurocirugía y/o cirugía otorrinolaringológica, debido a que es una patología potencialmente grave. El diagnóstico es clínico e imagenológico, y requiere de un alto índice de sospecha. Un manejo oportuno es relevante para prevenir la herniación y la muerte. Pneumocephalus refers to the presence of air in the cranial cavity, and in general, is self-limited and asymptomatic. It can occur after trauma, craniofacial surgery, due to congenital defects, infection, neoplasia or spontaneously. Tension pneumocephalus is a neurosurgical emergency in which intracranial air accumulates continuously, causing a mass effect. It presents with headache and marked neurological deterioration. Despite being rare, it is relevant to consider tension pneumocephalus as a possible complication in patients with a history of neurosurgery and/or otolaryngology surgery, as it can be life-threatening. Diagnosis requires a high index of suspicion and imagenologic confirmation. Timely management is relevant to prevent herniation and death.
Current status of the diagnosis of developmental dysplasia of the hips in the 21st Century
(2023) Pérez, Lizbet; Besomi, Javier; Fuentealba, Isabel
Inspired by an article on developmental dysplasia of the hips (DDH) from the mid-20th century, we present an updated examination of the epidemiology, etiology, risk factors, and natural history of this condition. We provide a concise overview of essential concepts and definitions crucial for an accurate diagnostic approach. We assess the current significance of imaging in the diagnostic process, with a particular focus on AP pelvic radiography the prevailing imaging modality employed in our country for diagnosis. We elucidate our own method, termed HI-RADS, for analyzing and reporting AP pelvic X-rays in the context of universal screening at three months. Furthermore, we discuss various ultrasound techniques for diagnosis and advocate for their combined static and dynamic utilization. We emphasize the critical need for early detection to prevent potential complications, a practice adopted by several countries; however, achieving a consensus on its implementation remains an ongoing challenge. Inspirados en un artículo sobre displasia del desarrollo de las caderas (DDC) escrito a mediados del siglo XX, presentamos un análisis actualizado de la epidemiología, etiología, factores de riesgo e historia natural de esta enfermedad. Recapitulamos los conceptos y definiciones fundamentales necesarios para abordar un diagnóstico adecuado. Examinamos el papel de las imágenes en el diagnóstico, destacando la Radiografía de pelvis AP (anteroposterior), la modalidad más empleada en nuestro país para este propósito. Describimos el método que hemos desarrollado, denominado HI-RADS, para analizar e informar las Radiografías de pelvis AP en el contexto de la pesquisa universal a los tres meses. Abordamos las diversas técnicas ecográficas disponibles para el diagnóstico, recomendando la utilización combinada de enfoques estáticos y dinámicos. Enfatizamos la importancia de una detección temprana para prevenir secuelas, práctica que se lleva a cabo en varios países, aunque aún existe falta de consenso en cuanto a su implementación.
Assessing diabetic polyneuropathy in Spanish-speakingpatients: Translation and validation of the TorontoClinical Neuropathy Score
(2023) Idiáquez, Juan Francisco; Acosta, Ignacio; Prat, lberto; Gattini, Francesca; Pino, Francisca; Barnett, Carolina
Background and aims: Diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes. The Toronto Clinical Neuropathy Score (TCNS) is a useful tool for detecting DSP. However, it is not available in Spanish. The study aimed to translate and culturally adapt the TCNS and modified (mTCNS) scales into Spanish and evaluate their measurement properties. Methods: A multistep forward-backward method was used for translation and cultural adaptation. A panel of physicians subjected the final Spanish versions of TCNS and mTCNS (TCÑS, mTCÑS) to cognitive debriefing. Consecutive patients with diabetes mellitus and DSP were recruited from an outpatient clinic, and the TCÑS and mTCÑS were tested for construct validity, along with other measures. Results: The internal consistency of both TCÑS and mTCÑS was excellent, as evidenced by Cronbach's Alpha coefficients of 0.83 and 0.85, respectively. Furthermore, there was a robust positive correlation between TCÑS and mTCÑS. In addition, TCÑS was found to exhibit a strong negative correlation with sural sensory nerve action potential amplitude (r = -0.9206) and peroneal compound motor action potential amplitude (r = -0.729), while demonstrating a positive and strong correlation with the Michigan Neuropathy Screening Instrument (r = 0.713). Interpretation: The TCÑS and mTCÑS are reliable and valid translations of the original TCNS. The TCÑS and mTCÑS can be used to diagnose and measure the severity of neuropathy in Spanish-speaking patients with diabetes.

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