Browsing by Author "Alvarado, Juan"
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Publication Development and internal validation of a multifactorial riskprediction model for gallbladder cancer in a high-incidencecountry(2023) Boekstegers, Felix; Scherer, Dominique; Barahona, Carol; Marcelain, Katherine; Gárate, Valentina; Waldenberge, Melanie; Morales, Erik; Rojas, Armando; Munoz, César; Retamales, Javier; De Toro, Gonzalo; Barajas, Olga; Rivera, María; Cortés, Analía; Loader, Denisse; Saavedra, Javiera; Gutiérrez, Lorena; Ortega, Alejandro; Bertrán, Maria; Bartolotti, Leonardo; Gabler, Fernando; Campos, Monica; Alvarado, Juan; Moisán, Fabricio; Spencer, Loreto; Nervi, Bruno; Carvajal-Hausdorf, Daniel; Losada, Héctor; Almau, Mauricio; Fernández, Plinio; Olloquequi, Jordi; Fuentes, Macarena; Gonzalez, Rolando; Bortolin, Maria; Acuña, Victor; Gallo, Carla; Ruiz, Andres; Rothhamme, Francisco; Bermejo, JustoSince 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non-genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision-recall curve (AUC-PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC-PRC for the Baseline Model (0.44%, 95%CI 0.42-0.46) increased by 0.22 (95%CI 0.15-0.29) when non-genetic factors were included, and by 0.25 (95%CI 0.20-0.30) when incorporating non-genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104-131) decreased to 92 (95%CI 60-128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59-110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non-genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.Publication Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers(2023) Zollner, Linda; Boekstegers, Felix; Barahona, Carol; Scherer, Dominique; Marcelain, Katherine; Gárate, Valentina; Waldenberger, Melanie; Morales, Erik; Rojas, Armando; Munoz, César; Retamales, Javier; De Toro, Gonzalo; Vera, Allan; Barajas, Olga; Rivera, María; Cortés, Analía; Loader, Denisse; Saavedra, Javiera; Gutiérrez, Lorena; Ortega, Alejandro; Bertrán, Maria; Bartolotti, Leonardo; Gabler, Fernando; Campos, Mónica; Alvarado, Juan; Moisán, Fabricio; Spencer, Loreto; Nervi, Bruno; Carvajal-Hausdorf, Daniel; Losada, Héctor; Almau, Mauricio; Fernández, Plinio; Olloquequi, Jordi; Carter, Alice; Miquel, Juan; Bustos, Bernabe; Fuentes, Macarena; Gonzalez, Rolando; Bortolini, Maria; Acuña, Victor; Gallo, Carla; Ruiz, Andres; Rothhammer, Francisco; Bermejo, JustoA strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10-5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate -0.006 kg/m2, 95% CI -0.009 to -0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.Publication Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression(2022) Blandino, Alice; Scherer, Dominique; Rounge, Trine B.; Umu, Sinan U.; Boekstegers, Felix; Barahona Ponce, Carol; Marcelain, Katherine; Gárate-Calderón, Valentina; Waldenberger, Melanie; Morales, Erik; Rojas, Armando; Muñoz, César; Retamales, Javier; Toro, Gonzalo de; Barajas, Olga; Rivera, María Teresa; Cortés, Analía; Loader, Denisse; Saavedra, Javiera; Gutiérrez, Lorena; Ortega, Alejandro; Bertrán, María Enriqueta; Gabler, Fernando; Campos, Mónica; Alvarado, Juan; Fabrizio Moisán 18, Loreto Spencer 18, Bruno Nervi 19, Daniel E Carvajal-Hausdorf; Spencer, Loreto; Nervi, Bruno; Carvajal-Hausdorf, Daniel; Losada, Héctor; Almau, Mauricio; Fernández, Plinio; Gallegos, Iván; Olloquequi, Jordi; Fuentes-Guajardo, Macarena; González -Jose, Rolando; Bortolini, María Cátira; Gallo, Carla; Ruíz Linares, Andrés; Rothhammer, Francisco; Bermejo, Justo LorenzoLong noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence "gallstones → dysplasia → GBC". In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p-value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p-value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r2 = 0.26) and three cis-C22orf34-eQTLs (r2 = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR = 1.25 per log2 expression unit, 95% CI 1.04-1.52, p-value = 0.02). Our results suggest that preselection of lncRNAs based on tissue samples and exploitation of cis-lncRNA-eQTLs may facilitate the identification of circulating noncoding RNAs linked to cancer risk.Item Subcutaneous lipoatrophy and skin depigmentation secondary to TMJ intra-articular corticosteroid injection(Elsevier, 2017) Skármeta, Nicolás; Hormazábal, Fernando; Alvarado, Juan; Rodriguez, AnaChronic orofacial pain is a complex multidimensional experience that produces disability and impairment of normal mandibular function. Overall estimations of chronic orofacial pain prevalence are 7 to 11% of the general population. Temporomandibular disorders (TMDs) are one of the most prevalent chronic orofacial pain conditions, with temporomandibular joint (TMJ) arthralgia accounting for 30.1% of TMD patients. Interventional procedures are often used in pain and palliative medicine to achieve reasonable and cost-effective pain relief. The use of intra-articular corticosteroids in relieving arthralgia and improving joint function has been well documented. We present the clinical case of an 84-year-old female patient who presented to the Hospital del Salvador orofacial pain service with preauricular pain, limited range of motion, provoked pain at palpation, and decreased function in the preauricular region. In accordance with the DC/TMD criteria, left TMJ arthralgia and degenerative joint disease was diagnosed and was later corroborated by cone beam computed tomography. An intra-articular injection of 10 mg of methylprednisolone was prescribed, and the patient underwent the procedure in accordance with Hospital del Salvador's intra-articular injection protocol. The patient underwent the intervention without any inconvenience. At the 3-week follow-up visit, the patient presented with a depigmented depression zone adjacent to the site of injection. After echotomography, we concluded that the patient had developed skin depigmentation and subcutaneous lipoatrophy related to the intra-articular injection of methylprednisolone. To the best of our knowledge, this is the first report of this complication secondary to an interventional procedure in the TMJ. Clinicians should be aware of, and patients must be advised of, this rare complication before an intra-articular intervention.Item Validation of a Visual-Spatial Secondary Task to Assess Automaticity in Laparoscopic Skills(2018) Castillo, Richard; Alvarado, Juan; Moreno, Pablo; Billeke, Pablo; Martínez, Carlos; Varas, Julián; Jarufe, NicolásINTRODUCTION: Our objective was to assess reliability and validity of a visual-spatial secondary task (VSST) as a method to measure automaticity on a basic simulated laparoscopic skill model. In motor skill acquisition, expertise is defined by automaticity. The highest level of performance with less cognitive and attentional resources characterizes this stage, allowing experts to perform multiple tasks. Conventional validated parameters as operative time, objective assessment skills scales (OSATS), and movement economy, are insufficient to distinguish if an individual has reached the more advanced learning phases, such as automaticity. There is literature about using a VSST as an attention indicator that correlates with the automaticity level. METHODS: Novices with completed and approved Fundamentals of Laparoscopic Surgery course, and laparoscopy experts were enrolled for an experimental study and measured under dual tasks conditions. Each participant performed the test giving priority to the primary task while at the same time they responded to a VSST. The primary task consisted of 4 interrupted laparoscopic stitches (ILS) on a bench-model. The VSST was a screen that showed different patterns that the surgeon had to recognize and press a pedal while doing the stitches (PsychoPsy software, Python, MacOS). Novices were overtrained on ILS until they reach at least 100 repetitions and then were retested. Participants were video recorded and then assessed by 2 blinded evaluators who measured operative time and OSATS. These scores were considered indicators of quality for the primary task. The VSST performance was measured by the detectability index (DI), which is a ratio between correct and wrong detections. A reliable evaluation was defined as two measures of DI with less than 10% of difference, maintaining the cutoff scores for performance on the primary task (operative time <110 seg and OSATS > 17 points). RESULTS: Novices (n = 11) achieved reliable measure of the test after 2 (2-5) repetitions on the preassessment and 3.75 (2-5) on the postassessment (p = 0.04); whereas laparoscopy experts (n = 4) did it after 3.5 (3-4) repetitions. Proficiency cutoff scores for the primary task were achieved on every measure for novices (prepost over-training) and experts. Expert performance on VSST was DI 0.78 (0.69-0.87). Novice performance was significantly better on postassessment (DI-pre 0.48 [0.06-0.71] vs DI-post 0.78 [0.48-0.95], p = 0.003). Overtraining consisted in 140 (100-210) repetitions of ILS for all novices, made in 8 hours (3-15). By categorizing DI based on expert performance, novices with DI-post > 0.65 achieved better OSATS score and less operative time than novices with DI-post < 0.65 (p = 0.007 y, p = 0.089, respectively). CONCLUSION: Measuring automaticity is feasible using a VSST. This instrument is reliable and has a face, content and construct validity. A DI over 0.65 may be a cutoff point correlated with high standard performance on the primary task. This instrument measures performance on laparoscopic skills and along with conventional indicators, would better define advance levels of expertise. More studies are required applying this VSST to achieve external validity by reproducing our results. (C) 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.