Chilean Patients Research Articles

Historical and Molecular Perspectives on the Presence of Helicobacter pylori in Latin America: A Niche to Improve Gastric Cancer Risk Assessment.

Helicobacter pylori (H. pylori) is responsible for causing chronic gastritis, which can cause peptic ulcer and premalignant lesions such as atrophic gastritis, intestinal metaplasia, and dysplasia, with the risk of developing gastric cancer. Recent data describe that H. pylori colonizes the gastric mucosa of more than 50% of the world's population; however, this bacterium has been described as infecting the human population since its prehistory. This review focuses on the populations and subpopulations of H. pylori, differentiated by the polymorphisms present in their constitutive and virulence genes. These genes have spread and associated with different human populations, showing variability depending on their geographical distribution, and have evolved together with the human being. The predominant genotypes worldwide, Latin America and Chile, are described to understand the genetic diversity and pathogenicity of H. pylori in different populations and geographic regions. The high similarity in the sequence of virulence genes between H. pylori strains present in Peruvian and Spanish natives in Latin America suggests a European influence. The presence of cagA-positive strains and vacA s1 m1 allelic variants is observed with greater prevalence in Chilean patients with more severe gastrointestinal diseases and is associated with its geographical distribution. These findings highlight the importance of understanding the genetic diversity of H. pylori in different regions of the world for a more accurate assessment of the risk of associated diseases and their potential impact on health.

P1133 Relative survival and cause-specific mortality of a Chilean Inflammatory Bowel Disease cohort

Abstract Background In the past two decades, multiple studies have shown an improvement in outcomes of inflammatory bowel disease (IBD) patients including a decreasing mortality associated with new treatments, surveillance, and healthcare support. There are no large studies in Latin-American countries addressing survival and death causes in IBD patients. We aimed to assess relative survival (RS) and causes of death in Chilean IBD patients. Methods IBD patients treated in a tertiary reference centre (Pontificia Universidad Católica of Chile, Santiago, Chile) since January 1990 were included in a local database. Death certificates were analysed to obtain the date and specific cause of death. The recorded time started on the date of definitive diagnosis and lasted until death or censoring on December 31st, 2020. The survival of IBD patients was compared with the life expectancy of the Chilean general population based on official life tables collected in the Human Mortality Database (www.mortality.org). The RS was computed using the Ederer II method implemented in the RELSURV package of the R software. A RS greater than 1.0 indicates that the analysed cohort has a higher survival than the expected survival of the reference population for the same age, sex and date at which age was coded. Inclusion of 1.0 within 95% CI indicates no difference between observed and expected survival. Data were also expressed graphically as the observed cumulative survival curves over time and the 95% confidence interval (CI) and compared to the reference population. Results We included 1,289 IBD patients with a media age at diagnosis of 35.9±14 years, 40.9% males and a follow-up of 22,525 patients-year. Ulcerative Colitis, Crohn’s disease and IBD unclassified patients comprised 50.2%, 43.1% and 6.7% of the cohort, respectively. A total of 106 patients (8.9%) died during the study period. Compared with the general population, the survival of IBD patients was higher (RS = 1.04; 95% CI: 1.02-1.07) at 20 years of follow-up (Table and Figure). This higher RS in IBD patients was observed in males and females, as well as CD patients and IBD patients older than 40-year-old (Table). The main causes of death in IBD patients were cancer (34%), infections (27.7%) and cardiovascular diseases (21.3%). Conclusion Compared to the general population, a higher long-term survival was observed in this large cohort of Chilean IBD patients. These findings may be due to a closer surveillance of this group of patients. Causes of death mirrored those in previously reported cohorts; therefore, a special care should be pay on their prevention in Latin-American countries as well.

Quality of life, exercise capacity, cognition, and mental health of Chilean patients after COVID-19: an experience of a multidisciplinary rehabilitation program at a physical and rehabilitation medicine unit.

Post-COVID disabilities, encompassing physical, cognitive, and psychological aspects, constitute the primary health sequelae for survivors. While the rehabilitation needs post COVID-19 are now well understood, each country possesses unique characteristics in terms of populations, healthcare systems, social dynamics, and economic profiles, necessitating context-specific recommendations. This study aims to address two main objectives: (1) analyze the impact of an 8-week multidisciplinary rehabilitation program on the quality of life, functional capacity, cognition, and mental health adaptations in adults recovering from COVID-19 in northern Chile, and (2) propose a personalized model for predicting program dropouts and responses. A total of 44 subjects were enrolled, forming two groups during the study: a treatment group (n = 32) and a dropout group (n = 12). The treatment group participated in the 8-week multidisciplinary rehabilitation program. The results indicate that (1) After 8 weeks, the quality of life of the patients in the treatment group exhibited significant improvements reflected in all aspects of the Short Form-36 Health Survey (SF36, p < 0.005) and the total score (p < 0.001), with a concurrent decrease in dysfunctionality (p < 0.001). (2) Significant improvements were also observed in various physical performance tests, including the: 6-minute walk test, 1-min sit-to-stand, dynamometry, Tinetti balance, and Berg score (p < 0.001). Moreover, physical therapy led to a reduction in neuropathic symptoms and pain, psychological therapy reduced anxiety and depression, and language therapy enhanced memory and speech (all p < 0.05). (3) Demographic and clinical history characteristics did not predict responses to rehabilitation. (4) A regression model for predicting changes in SF-36 total score, based on physical function, physical role, general health, and mental health, was established based on the data from study (p < 0.01, adjusted R2 = 0.893). (5) Classification models for predicting dropouts achieved 68% accuracy, with key predictors of treatment adherence including diabetes, hypertension, and dyslipidemia, Tinetti balance, physical role, and vitality of SF36, and performance on the 6-minute walk test and 1-minute sit-to-stand. This study demonstrates significant enhancements in quality of life, improved functional performance, and reductions in mental and cognitive burdens within an 8-week rehabilitation program. Additionally, it is possible to identify patients at risk of dropping out using cost-effective, outpatient, and clinically applicable tests.

Secondary Acute Myeloid Leukemia from a Previous Chronic Myeloproliferative Neoplasm: A Study of Grelam-Chile Concerning Chilean Patients on Behalf of AML Pethema Registry

Introduction: Secondary Acute Myeloid Leukemia (sAML) from Chronic Myeloproliferative Neoplasm (chMPN) is associated with an unfavorable prognosis and is characterized by a unique set of cytogenetic and molecular features distinct from de novo AML. The only cure for these patients is allogeneic Stem Cell Transplantation (SCT), which usually is not possible given the advanced age and comorbidities from this patient population. Methods: We present a retrospective analysis of sAML Chilean patients due to chMPN from the multicentric epidemiological registry of AML of the PETHEMA Spanish Group. Results: There are 802 AML Chilean patients incorporated in the online PETHEMA platform. 158 are sAMLand 26 are secondary to chMPN. Compared with the sAML group, patients with previous chMPN were mainly male (56% vs. 76%, respectively), had a larger white blood cell count (32,720 mm3 vs. 61,130 mm3), and had splenomegaly (P &amp;lt;0.05). There was no difference in age (median 62,35 years old), peripheral blood blasts (media 28,8%), fibrinogen (287 mg/dl), or other laboratory tests (p&amp;gt;0.05). Regardless of the type of chMPN: Chronic Myeloid Leukemia: 8 patients: Chronic myelomonocytic leukemia: 5, Primary Myelofibrosis: 5, Chronic Myeloproliferative Syndrome not specified subtype: 6, Polycythemia Vera/essential Thrombocytosis 2. 50% received previously chemotherapy, mainly Tyrosine Kinase Inhibitors (7) and hydroxycarbamide (7). Regardless sAML % had an abnormal karyotype. Treatment used, it was Anthracycline/Daunorubicin (38%), azacytidine with or without Venetoclax (19%), and palliative care (23%). In the first induction, the rate of Complete response (CR), or complete response with incomplete hematological response (iCR), was reached in only 3 patients, and these had negative MRD. From the patients with partial responses, 9 patients received a second line of treatment, mainly azacytidine. After that, three more patients reached CR. Only one patient received allogeneic SCT. The average stay in the hospital was 41,4 days, and Overall survival (OS) was 12,2 months (OS in all sAML was 14,2 months, N.S. p&amp;gt;0.05). The mortality rate was 84%, and the main cause was progressive disease in 60% of those cases. Conclusion: We present our local experience with this type of sAML. The outcome remains poor; it seems that allogeneic SCT is the only cure, but most patients cannot reach it. More research is needed to improve the high rates of mortality for this patient population.

Amerindian ancestry proportion as a risk factor for inflammatory bowel diseases: results from a Latin American Andean cohort.

Latin American populations remain underrepresented in genetic studies of inflammatory bowel diseases (IBDs). Most genetic association studies of IBD rely on Caucasian, African, and Asian individuals. These associations have yet to be evaluated in detail in the Andean region of South America. We explored the contribution of IBD-reported genetic risk variants to a Chilean cohort and the ancestry contribution to IBD in this cohort. A total of 192 Chilean IBD patients were genotyped using Illumina's Global Screening Array. Genotype data were combined with similar information from 3,147 Chilean controls. The proportions of Aymara, African, European, and Mapuche ancestries were estimated using the software ADMIXTURE. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for gender, age, and ancestry proportions. We also explored associations with previously reported IBD-risk variants independently and in conjunction with genetic ancestry. The first and third quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7 and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52-3.48) for the lowest vs. the highest group. Only one variant (rs7210086) of the 180 reported IBD-risk SNPs was associated with IBD risk in the Chilean cohort (adjusted P = 0.01). This variant is related to myeloid cells. The type and proportion of Native American ancestry in Chileans seem to be associated with IBD risk. Variants associated with IBD risk in this Andean region were related to myeloid cells and the innate immune response.

Exploring the clinical and genetical spectrum of ADPKD in Chile to assess ProPKD score as a risk prediction tool

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition associated primarily with PKD1 and PKD2 genes. However, ADPKD patients in Latin America have had limited access to comprehensive care. The ProPKD score predicts the likelihood of kidney failure before the age of 60. This study aimed to describe the clinical and genetic characteristics of Chilean ADPKD patients and assess the ProPKD score.MethodsWe enrolled 40 ADPKD probands and 122 relatives from different centers. Genetic analysis of PKD1 and PKD2 genes was performed by combining direct and next-generation sequencing. Pathogenicity was determined using bioinformatic tools. ProPKD scores were calculated based on clinical and genetic data.ResultsADPKD probands were diagnosed at a median age of 35 years. Pathogenic, likely pathogenic, or uncertain significance variants were identified in 38/40 pedigrees, with 89% involving PKD1 and 11% involving PKD2 variants. Among the identified variants, 62% were novel. Patients with PKD1 truncating variants had a more severe disease course, reaching kidney failure by a median age of 48.5 years. ProPKD scores were assessed in 72 individuals, stratifying them into high-, intermediate-, or low-risk categories and the median ages for kidney failure were 45, 49, and 52 years, respectively (log-rank p = 0.001).ConclusionThis study provides valuable insights into the clinical and genetic profiles of ADPKD patients in Chile. ADPKD poses a significant public health concern, warranting improvements in diagnosis and treatment. The use of the ProPKD score to predict disease progression should be further explored to enhance patient care and management.

5 years DKMS Chile: approach, results and impact of the first unrelated stem cell donor center in Chile.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed worldwide to treat blood cancer and other life-threatening blood disorders. As successful transplantation requires an HLA-compatible donor, unrelated donor centers and registries have been established worldwide to identify donors for patients without a family match. Ethnic minorities are underrepresented in large donor registries. Matching probabilities are higher when donors and patients share the same ethnic background, making it desirable to increase the diversity of the global donor pool by recruiting donors in new regions. Here, we report the establishment and the first 5 years of operation of the first unrelated stem cell donor center in Chile, a high-income country in South America with a population of over 19 million. We used online and in-person donor recruitment practices through patient appeals and donor drives in companies, universities, the armed forces, and public services. After confirmatory typing donors were subjected to medical work-up and cleared for donation. We recruited almost 170,000 donors in 5 years. There were 1,488 requests received for confirmatory typing and donor availability checks, of which 333 resulted in medical work-up, leading to 194 stem cell collections. Products were shipped to Chile (48.5%) and abroad. Even when the COVID-19 pandemic challenged our activities, the number of donors recruited and shipped stem cell products remained steady. In Chile there was an almost 8-fold increase in unrelated donor transplantation activity from 16 procedures in 2016-2018 to 124 procedures in 2019-2021, mainly for pediatric patients following the center's establishment. We estimate that 49.6% of Chilean patients would find at least one matched unrelated donor in the global DKMS donor pool. Establishing a DKMS donor center in Chile has significantly increased donor availability for Chilean patients and contributed to an increase of unrelated donor stem cell transplant activity.

Genotype Prevalence of Lactose Deficiency, Vitamin D Deficiency, and the Vitamin D Receptor in a Chilean Inflammatory Bowel Disease Cohort: Insights from an Observational Study.

Lactose intolerance (LI) and vitamin D deficiency (VDD) have been linked to inflammatory bowel disease (IBD). We conducted an observational study in 192 Chilean IBD patients to investigate the prevalence of a specific gene variant (LCT-13910 CC genotype) associated with LI and the prevalence of VDD/Vitamin D Receptor (VDR) gene variants. Blood samples were analyzed using Illumina's Infinium Global Screening Array. The LCT-13910 CC genotype was found in 61% of IBD patients, similar to Chilean Hispanic controls and lower than Chilean Amerindian controls. The frequency of the LCT-13910-C allele in Chilean IBD patients (0.79) was comparable to the general population and higher than Europeans (0.49). Regarding VDR and VDD variants, in our study, the rs12785878-GG variant was associated with an increased risk of IBD (OR = 2.64, CI = 1.61-4.32; p-value = 0.001). Sixty-one percent of the Chilean IBD cohort have a genetic predisposition to lactose malabsorption, and a significant proportion exhibit genetic variants associated with VDD/VDR. Screening for LI and VDD is crucial in this Latin American IBD population.

The c.415C>T polymorphism in NUDT15 is more frequent than the polymorphisms in TPMT in Chilean patients who use thiopurine drugs.

The c.415C>T polymorphism in NUDT15 is more frequent than the polymorphisms in TPMT in Chilean patients who use thiopurine drugs.

The c.415C>T polymorphism in NUDT15 is more frequent than the polymorphisms in TPMT in Chilean patients who use thiopurine drugs.

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are drugs widely used in the treatment of autoimmune diseases. Among the enzymes involved in the metabolism of AZA and 6-MP are thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15). The existence of single nucleotide polymorphisms in the genes that code for these enzymes could decreased enzymatic activity AND lead to severe myelosuppression. The most relevant polymorphism is NUDT15*3 (rs116855232), where the replacement of cytosine for thymine at position 415, which in turn leads to a loss of enzymatic activity. In a previous study, it was identified that together the polymorphisms in the TPMT gene reach an allelic frequency of 3.81%. There is no information regarding the rs116855232 polymorphism in the NUDT15 gene, so this corresponds to the objective of this report. Blood samples from Chilean adult patients with indications for the use of AZA or 6-MP for different pathologies and who had undergone a TPMT gene polymorphism study were retrospectively analyzed. A total of 253 blood samples were analyzed. Of the 253 patients, 47 presented the c.415C>T polymorphism in the NUDT15 gene, 3 being homozygous and 44 heterozygous. Four of the heterozygous patients for NUDT15 also had the *3A variant in the TPMT gene, also heterozygous. The allelic frequency of the minor T allele found (9.88%) was very similar to that found in patients of Asian origin, and much higher than that reported for the European Caucasian or Latin American population.

Place of death in chilean patients with advanced cancer: A retrospective cohort study

Place of death in chilean patients with advanced cancer: A retrospective cohort study

Mediterranean diet and psychological well-being intervention to reverse metabolic syndrome in Chile (CHILEMED trial)

Psychosocial status and lifestyle are key risk factors of non-communicable diseases (NCDs), which, in turn, are main drivers of healthcare costs and morbimortality worldwide, including Chile. Mediterranean diet (MedDiet) is one of the healthiest dietary patterns under study. However, its impact on high-risk conditions, such as metabolic syndrome (MetS), and NCDs outside the Mediterranean Basin remains mostly unexplored. Even though Central Chile has an environment, food production, and culinary traditions comparable to those present in Mediterranean countries, few studies -some with significant methodological limitations- have evaluated the effect of MedDiet on health and/or disease in Chilean subjects. Importantly, a Mediterranean lifestyle is a modus vivendi that integrates physical health with mental and social well-being. Psychological well-being (PWB) is associated with healthy behaviors, positive health outcomes, and longevity, thereby emerging as a novel healthcare goal. We report here an ongoing randomized controlled clinical trial in Chilean patients with MetS seeking to test whether (1) a PWB theory-based intervention facilitates induction to and increases long-term adherence to a locally adapted MedDiet, and (2) a MedDiet intervention -implemented alone or combined with well-being promotion- is more effective at reversing MetS compared to individuals following a low-fat diet without psychological support. The CHILEan MEDiterranean (CHILEMED) diet intervention study is a 1-year trial including patients with MetS living in Chile. Participants will be assigned randomly by a computer-generated random number sequence to one of the three intervention arms: a) low-fat diet as control group, b) MedDiet alone, and c) MedDiet plus well-being support. Patients will be followed-up by individual and/or group online nutritional sessions or phone cal as well as 6- and 12-month in-person re-assessment of medical history, medication use, food intake, PWB, anthropometrics/physical exam, and blood collection for laboratory analysis. The primary outcome of the trial will be the effect of the MedDiet -with or without PWB intervention- on overall reversal of MetS compared to low-fat diet alone. Based on a statistical superiority trial, expected impact, and patient loss, the estimated study sample is 339 subjects (113 individuals per arm in 3 equal-sized groups). Currently, we have enrolled 179 patients, predominantly women, evenly distributed by age (group means ranging from 45.7 to 48,9 years-old), 3/4 are obese with almost all of them showing abdominal obesity, 70% are hypertensive, whereas <10% exhibit diabetes. If findings turn out as expected (e.g., MedDiet -with or without PWB intervention- is better than the low-fat diet for reversion of MetS at 1-year follow-up), CHILEMED will provide further beneficial evidence of the MedDiet on NCD risk conditions beyond the Mediterranean region.

Development and validation of nonalcoholic fatty liver disease test: a simple sensitive and specific marker for early diagnosis of nonalcoholic fatty liver disease.

This study aimed to develop a noninvasive test for identifying patients with nonalcoholic fatty liver disease (NAFLD) based on clinical and routine laboratory data. The developed model 'NAFLD test' was compared to the most commonly used NAFLD scores and then validated in three groups of NAFLD patients from five centers in Egypt, China, and Chile. Patients were divided into the discovery cohort (n = 212) and the validation study (n = 859). The ROC curve and stepwise multivariate discriminant analysis were used to develop and validate the NAFLD test and evaluate its diagnostic performance, which was then compared to other NAFLD scores. Elevated C-reactive protein (CRP), cholesterol, BMI, and alanine aminotransferase (ALT) levels were significantly associated with NAFLD (P < 0.0001). NAFLD test is depicted as (-0.695 + 0.031 × BMI + 0.003 × cholesterol + 0.014 × ALT + 0.025 × CRP) to discriminate patients with NAFLD from healthy individuals. The area under the ROC curve (AUC) of the NAFLD test was 0.92 [95% confidence interval (CI): 0.88-0.96]. The NAFLD test was the most accurate diagnostic indicator of NAFLD when compared to widely used NAFLD indices. Upon validating the NAFLD test, its AUC (95% CI) for distinguishing patients with NAFLD from healthy individuals was 0.95 (0.94-0.97), 0.90 (0.87-0.93), and 0.94 (0.91-0.97) in Egyptian, Chinese, and Chilean patients with NAFLD respectively. The NAFLD test is a new validated diagnostic biomarker that can be utilized for the early diagnosis of NAFLD with high diagnostic performance.

Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country.

Since 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.

HLA allele and haplotype frequencies of registered stem cell donors in Chile.

Patients in need of hematopoietic stem cell transplantation often rely on unrelated stem cell donors matched in certain human leukocyte antigen (HLA) genes. Donor search is complicated by the extensive allelic variability of the HLA system. Therefore, large registries of potential donors are maintained in many countries worldwide. Population-specific HLA characteristics determine the registry benefits for patients and also the need for further regional donor recruitment. In this work, we analyzed HLA allele and haplotype frequencies of donors of DKMS Chile, the first Chilean donor registry, with self-assessed "non-Indigenous" (n=92,788) and "Mapuche" (n=1,993) ancestry. We identified HLA alleles that were distinctly more abundant in the Chilean subpopulations than in worldwide reference populations, four of them particularly characteristic for the Mapuche subpopulation, namely B*39:09g, B*35:09, DRB1*04:07g, and DRB1*16:02g. Both population subsamples carried haplotypes of both Native American and European origin at high frequencies, reflecting Chile's complex history of admixture and immigration. Matching probability analysis revealed limited benefits for Chilean patients (both non-Indigenous and Mapuche) from donor registries of non-Chilean donors, thus indicating a need for ongoing significant donor recruitment efforts in Chile.

Atopic Dermatitis in Latin America: Considerations on Epidemiology, Clinical and Laboratory Features, Ethnic/Racial Variations, and Therapeutic Management.

Latin America (LA) encompasses about 8.5% of the world's population, exhibits ethnic/racial heterogeneity and social inequality. We hereby present a 20-year literature review (2004-2023) on epidemiology, diagnosis, clinical and laboratory features, quality of life and management of atopic dermatitis (AD) in LA. Highest AD prevalence for children aged 6-7 years was reported in Ecuador (22.5%) and Colombia (20.9%), for adolescents in Colombia (24.6%) and for all ages, in Brazil (20.1%). Regions with a predominantly Black population in LA varied significantly, ranging from 4.4% in Northern Brazil to 10.1% in Cuba, indicating genetic variation among African subgroups. Filaggrin loss-of-function mutations showed variants seen in Europeans in 9.3% of Chilean patients and studies in Brazil revealed impaired expression of filaggrin and claudin-1 in the skin but increased expression in conjunctival epithelia of AD patients. The most reported AD features included erythema, pruritus, and dry skin, with marked lichenification. Severe pruritus was reported by 54.4% of patients and a high impact on quality of life was detected in 50% of adults with AD. In Brazilian referral hospitals, 65.6% of patients were classified as having severe AD, and 56% had one or more hospitalizations during their lifetime, indicating a need for better disease control. Diagnosing AD is challenging due to broad clinical features, ethnoracial variations and lack of universal diagnostic criteria. Furthermore, lack of physician training, barriers to medication access, and socioeconomic inequalities hinder effective disease management in LA.

Obesity Is Associated with Changes in Laboratory Biomarkers in Chilean Patients Hospitalized with COVID-19.

It is reported that patients with obesity are more frequently hospitalized for COVID-19, and evidence exists that obesity is a risk factor, regardless of other comorbidities. The objective of this study was to evaluate the association of obesity with changes in laboratory biomarkers in hospitalized Chilean patients. A total of 202 hospitalized patients (71 with obesity and 131 without obesity) with a diagnosis of COVID-19 were included in the study. Demographic, clinical, and laboratory (days 1, 3, 7, 15) data were obtained. We performed a statistical analysis, assuming significance with a value of p < 0.05. Significant differences in chronic respiratory pathology are observed between patients with and without obesity. The inflammatory markers CPR, ferritin, NLR, and PLR are elevated during the evaluated period, while changes in leukocyte populations are present on day 1 (eosinophils) and day 3 (lymphocytes). Finally, a persistent elevation of D-dimer level is observed, presenting significant differences on day 7 between patients with and without obesity. Obesity had a positive correlation with admission to the critical patient unit, invasive mechanical ventilation, and length of hospital stay. Patients with obesity hospitalized for COVID-19 present marked elevations of inflammatory and hemostasis parameters, with a correlation between obesity, changes in laboratory biomarkers, and the risk of adverse clinical outcomes also observed.

Genotype and Phenotype Characterization of Patients with Mucopolysaccharidosis IV-A in Chile

Introduction: Morquio syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an autosomal recessive disease caused by biallelic variants in the GALNS gene, encoding the lysosomal enzyme GalN6S, responsible for glycosaminoglycan keratan sulfate and chondroitin-6-sulfate degradation. Studies have shown that the degree of evolutionary and chemical divergence of missense variants in GalN6S when compared to ancestral amino acids is associated with the severity of the syndrome, suggesting a genotype-phenotype correlation. There is little information on Latin American patients with MPS IV-A that replicate these findings. This study aimed to characterize the phenotype and genotype from patients with MPS IV-A, who are under Enzyme Replacement Therapy at the Children’s Neuropsychiatry Service of the Hospital Clínico San Borja Arriarán, Santiago, Chile, and to determine if there is any association between genotype and phenotype with those findings. Methods: Information was collected from medical charts, all patients went through a GalN6S enzymatic activity measurement in leukocytes from peripheral blood, and the GALNS gene was sequenced for all cases. Results: 12 patients with MPS IV-A were recruited, all patients presented multisystem involvement, mostly skeletal, and 75% of cases underwent surgical interventions, and cervical arthrodesis was the most frequent procedure. In regards of the genotype, the two most frequent variants were c.319+2T>C (n = 10, 41.66%) and p.(Arg386Cys) (n = 8, 33.33%), the first one was previously described in 2018 in a patient from Chile [Bochernitsan et al., 2018]. Conclusion: This is the first time that a genotype-phenotype correlation has been studied by analyzing the variants effect on the molecular structure of human GalN6S and the evolutionary conservation degree of affected residues in a cohort of patients in Chile. Albeit our work could not find statistically significant associations, we may infer that the evolutionary conservations of affected amino acids and the effect of variants on enzyme structure may play a main role. Further analyzes should consider a meta-analysis of published cases with genotype data and larger samples and include other variables that could provide more information. Finally, our data strongly suggest that variant c.319+2T>C could have a founder effect in Chilean patients with MPS IV-A.

Access disparities and underutilization of germline genetic testing in Chilean breast cancer patients

Latin American reports on genetic cancer risk assessments are scarce. In Chile, current breast cancer (BC) guidelines do not define strategies for germline genetic testing. Our study sought to quantify the disparities in access to genetic testing in Chilean BC patients, according to international standards and their clinical characteristics to explore improvement strategies. Retrospective analysis of invasive BC databases including patients treated in a Public Hospital (PH) and in an Academic Private Center (AC) in Santiago, Chile between 2012 and 2021. Of 5438 BC patients, 3955 had enough data for National Comprehensive Cancer Network (NCCN) categorization. From these, 1911 (48.3%) fulfilled NCCN criteria for germline testing, of whom, 300 were tested for germline mutations and 268 with multigene panels. A total of 65 pathogenic variants were found in this subset. As expected, BRCA1/2 mutations were the most frequent (17.7%). Access to genetic testing was higher in AC versus PH (19.6% vs. 10.3%, p = 0.0001). Other variables associated with germline genetic testing were BC diagnosis after 2018, being 45years old or younger at diagnosis, BC family history (FH), FH of ovarian cancer, non-metastatic disease, and triple-negative subtype. In our cohort, 15% of BC patients who met NCCN criteria for germline testing were effectively tested. This percentage was evenlower at the PH. Current recommendations encourage universal genetic testing for BC patients; however, our findings suggest that Chile is far from reaching such a goal and national guidelines in this regard are urgently needed. To our knowledge, this is the first study of its kind in Chile and Latin America.

Abstract P3-03-19: Real-world data of clinical characteristics, risk factors and outcomes of Chilean triple-negative breast cancer patients

Abstract Background: triple-negative breast cancer (TNBC) is associated with hereditary and environmental risk factors plus an overall worse prognosis compared to other Breast Cancer (BC) subtypes. While TNBC risk factors, prevalence, clinical characteristics and prognosis may vary throughout different populations, limited data on Latin American patients forces clinical decisions to be based predominantly on data coming from non-Hispanic women. To obtain local epidemiological information, regarding risk factors and clinical outcomes, we analysed the largest Chilean BC registry. Methods: we conducted a retrospective population-cohort study involving females with any stage TNBC, treated at a community hospital (mid-low income) and at an academic private hospital (high income), between the years 2010 and 2021. Risk factors, reason for consultation, clinical and pathological characteristics and prognosis were separately analysed for both TNBC and non-TNBC subgroups. Univariate and multivariate analyses were performed to identify prognostic factors for survival on TNBC patients. Results: From 5,806 patients, 647 (11.2%) were identified as TNBC. Compared to non-TNBC patients, women were younger (median age 55.2 vs. 57.2, p=0.0001), with 15.8% of TNBC patients having been diagnosed before the age of 40 compared to 9.6% in non-TNBC (p= 0.0001). TNBC had a significantly lower screen-detected cancer rate (14.5% vs. 31.6% p= 0.0001) and worse stage at diagnosis. No differences were seen between patients seen at a community hospital and private centre, for both TNBC rate and stage. Other risk factors such as parity, age at first gestation, menarche, hormone therapy replacement and obesity showed no significant differences between TNBC and no-TNBC patients (table 1). With a median follow up of 57 months, 5-year overall survival (OS) and BC specific death were significantly shorter for TNBC compared to non-TNBC (76.4% vs 88.1% and 78.9% vs 91.2%, respectively; p=0.0001) (table 2). In the multivariate analysis, TN subtype (HR=2.3, p=0.0001), stage (HR=2.05 for stage II vs stage I, HR=7.04 for stage III vs. stage I, p=0.0001), lower income (HR= 1.64, p=0.0001), and non-screened detected BC (HR=1.32, p=0.03) were all associated with worse overall survival (table 3). Conclusion: This is the first study focusing on TNBC characteristics in Chilean BC patients and to our knowledge, the largest performed in a Latin American population. We identified a lower proportion of TNBC patients when compared with data reported from other LA groups and worldwide, a very low screen detected cancer rate and as expected significantly lower TNBC survival rate compared to non-TNBC women. While TNBC patients were younger compared to the non-TNBC group, this age difference was marginal compared to other reported studies. Community hospital patients (with mid-low income) were associated with lower survival rates for both all-cause mortality and BC specific survival, regardless of a similar stage distribution at diagnosis. Reflecting an underlying interaction between social and biological factors that needs to be addressed. Table 1. Patient characteristics: Triple-negative versus noN-triple negative breast cancer BMI: Body mass index; FH: Family history * Difference is statistically significant. Table 2. Survival comparison in triple-negative versus non-triple negative breast cancer * Difference is statistically significant. Table 3. Cox Regression Multivariate analysis * Difference is statistically significant. Citation Format: Benjamin Walbaum, FRANCISCO ACEVEDO, Catherine Bauerle, Mauricio Camus, Manuel Manzor, Raul Martinez, Paulina Veglia, Marisel Navarro, Constanza Guerra, Francisco Dominguez, Tomas Merino, Lidia Medina, CÉSAR SÁNCHEZ. Real-world data of clinical characteristics, risk factors and outcomes of Chilean triple-negative breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-19.