Death In Chile Research Articles

Chilean consensus by expert panel using the Delphi technique for primary and secondary prevention of gastric cancer

IntroductionGastric cancer (GC) is the first cause of cancer-related death in Chile and 6th in Latin America and the Caribbean (LAC). Helicobacter pylori (H. pylori) is the main gastric carcinogen, and its treatment reduces GC incidence and mortality. Esophageal-gastro-duodenoscopy (EGD) allows for the detection of premalignant conditions and early-stage GC. Mass screening programs for H. pylori infection and screening for premalignant conditions and early-stage GC are not currently implemented in LAC. The aim of this study is to establish recommendations for primary and secondary prevention of GC in asymptomatic standard-risk populations in Chile. MethodsTwo on-line synchronous workshops and a seminar were conducted with Chilean experts. A Delphi panel consensus was conducted over 2 rounds to achieve >80% agreement on proposed primary and secondary prevention strategies for the population stratified by age groups. Results10, 12, and 12 experts participated in two workshops and a seminar, respectively. In the Delphi panel, 25 out of 37 experts (77.14%) and 28 out of 52 experts (53.85%) responded. For the population aged 16–34, there was no consensus on non-invasive testing and treatment for H. pylori, and the use of EGD was excluded. For the 35–44 age group, non-invasive testing and treatment for H. pylori is recommended, followed by subsequent test-of-cure using non-invasive tests (stool antigen test or urea breath test). In the ≥45 age group, a combined strategy is recommended, involving H. pylori testing and treatment plus non-invasive biomarkers (H. pylori IgG serology and serum pepsinogens I and II); subsequently, a selected group of subjects will undergo EGD with gastric biopsies (Sydney Protocol), which will be used to stratify surveillance according to the OLGA classification (Operative Link for Gastritis Assessment); every 3 years for OLGA III–IV and every 5 years for OLGA I–II. ConclusionA “test-and-treat” strategy for H. pylori infection based on non-invasive studies (primary prevention) is proposed in the 35–44 age group, and a combined strategy (serology and EGD) is recommended for the ≥45 age group (primary and secondary prevention). These strategies are potentially applicable to other countries in LAC.

Estrategias para la prevención primaria y secundaria del cáncer gástrico: consenso chileno de panel de expertos con técnica Delfi

IntroductionGastric cancer (GC) is the first cause of cancer-related death in Chile and 6th in Latin America and the Caribbean (LAC). Helicobacter pylori (H. pylori) is the main gastric carcinogen, and its treatment reduces GC incidence and mortality. Esophageal-gastro-duodenoscopy (EGD) allows for the detection of premalignant conditions and early-stage GC. Mass screening programs for H. pylori infection and screening for premalignant conditions and early-stage GC are not currently implemented in LAC. The aim of this study is to establish recommendations for primary and secondary prevention of GC in asymptomatic standard-risk populations in Chile. MethodsTwo on-line synchronous workshops and a seminar were conducted with Chilean experts. A Delphi panel consensus was conducted over 2 rounds to achieve>80% agreement on proposed primary and secondary prevention strategies for the population stratified by age groups. Results10, 12, and 12 experts participated in two workshops and a seminar, respectively. In the Delphi panel, 25 out of 37 experts (77.14%) and 28 out of 52 experts (53.85%) responded. For the population aged 16-34, there was no consensus on non-invasive testing and treatment for H. pylori, and the use of EGD was excluded. For the 35-44 age group, non-invasive testing and treatment for H. pylori is recommended, followed by subsequent test-of-cure using non-invasive tests (stool antigen test or urea breath test). In the ≥45 age group, a combined strategy is recommended, involving H. pylori testing and treatment plus non-invasive biomarkers (H. pylori IgG serology and serum pepsinogens I and II); subsequently, a selected group of subjects will undergo EGD with gastric biopsies (Sydney Protocol), which will be used to stratify surveillance according to the classification Operative Link for Gastritis Assessment (OLGA); every 3 years for OLGA III-IV and every 5 years for OLGA I-II. ConclusionA “test-and-treat” strategy for H. pylori infection based on non-invasive studies (primary prevention) is proposed in the 35-44 age group, and a combined strategy (serology and EGD) is recommended for the ≥45 age group (primary and secondary prevention). These strategies are potentially applicable to other countries in LAC.

Towards closing socio-economic status disparities in COVID-19 premature mortality: a nationwide and trend analysis in Chile.

Socio-economic status (SES) disparities in coronavirus disease 2019 (COVID-19) mortality have been reported but complete information and time trends are scarce. In this study, we analysed the years of life lost (YLL) due to COVID-19 premature mortality during the pandemic in Chile and its evolution according to SES and sex compared with a counterfactual scenario [cerebrovascular accidents (stroke)]. We used Chile's national mortality databases from 2020 to 2022. YLL and age-standardized YLL and mortality rates by sex and by epidemic waves were determined. The 346 communes were stratified into SES groups according to their poverty index quintile. Negative binomial regression models were used to test trends. In >2 years of the pandemic, the COVID-19 YLL was 975 937, corresponding to 61 174 deaths. The YLL rate per 100 000 inhabitants was 1027 for males and 594 for females. There was a heterogeneous distribution of YLL rates and the regional level. Communes in the most advantaged SES quintile (Q5) had the highest YLL during the first wave compared with those in the lowest SES quintile (Q1) (P < 0.001) but the opposite was true during the second wave. COVID-19 YLL trends declined and differences between Q1 and Q2 vs Q5 converged from the second to the fourth waves (0.33 and 0.15, Ptrend < 0.001 and Ptrend = 0.024). YLL declined but differences persisted in stroke (-0.002, Ptrend = 0.979). COVID-19 deaths resulted in a higher impact on premature death in Chile, especially in men, with a heterogeneous geographic distribution along the territory. SES and sex disparities in COVID-19 premature mortality had narrowed by the end of the pandemic.

Humoral immunity against SARS-CoV-2 evoked by heterologous vaccination groups using the CoronaVac (Sinovac) and BNT162b2 (Pfizer/BioNTech) vaccines in Chile.

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) has caused over million deaths worldwide, with more than 61,000 deaths in Chile. The Chilean government has implemented a vaccination program against SARS-CoV-2, with over 17.7 million people receiving a complete vaccination scheme. The final target is 18 million individuals. The most common vaccines used in Chile are CoronaVac (Sinovac) and BNT162b2 (Pfizer-Biotech). Given the global need for vaccine boosters to combat the impact of emerging virus variants, studying the immune response to SARS-CoV-2 is crucial. In this study, we characterize the humoral immune response in inoculated volunteers from Chile who received vaccination schemes consisting of two doses of CoronaVac [CoronaVac (2x)], two doses of CoronaVac plus one dose of BNT162b2 [CoronaVac (2x) + BNT162b2 (1x)], and three doses of BNT162b2 [BNT162b2 (3x)]. We recruited 469 participants from Clínica Dávila in Santiago and the Health Center Víctor Manuel Fernández in the city of Concepción, Chile. Additionally, we included participants who had recovered from COVID-19 but were not vaccinated (RCN). We analyzed antibodies, including anti-N, anti-S1-RBD, and neutralizing antibodies against SARS-CoV-2. We found that antibodies against the SARS-CoV-2 nucleoprotein were significantly higher in the CoronaVac (2x) and RCN groups compared to the CoronaVac (2x) + BNT162b2 (1x) or BNT162b2 (3x) groups. However, the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups exhibited a higher concentration of S1-RBD antibodies than the CoronaVac (2x) group and RCN group. There were no significant differences in S1-RBD antibody titers between the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups. Finally, the group immunized with BNT162b2 (3x) had higher levels of neutralizing antibodies compared to the RCN group, as well as the CoronaVac (2x) and CoronaVac (2x) + BNT162b2 (1x) groups. These findings suggest that vaccination induces the secretion of antibodies against SARS-CoV-2, and a booster dose of BNT162b2 is necessary to generate a protective immune response. In the current state of the pandemic, these data support the Ministry of Health of the Government of Chile's decision to promote heterologous vaccination as they indicate that a significant portion of the Chilean population has neutralizing antibodies against SARS-CoV-2.

Early impact of COVID-19 vaccination on older populations in four countries of the Americas, 2021.

To estimate the early impact of coronavirus disease 2019 (COVID-19) vaccination on cases in older populations in four countries (Chile, Colombia, Guatemala, and the United States of America), and on deaths in Chile and Guatemala. Data were obtained from national databases of confirmed COVID-19 cases and deaths and vaccinations between 1 July 2020 and 31 August 2021. In each country, pre- and post-vaccination incidence ratios were calculated for COVID-19 cases and deaths in prioritized groups (50-59, 60-69, and ≥70 years) compared with those in the reference group (<50 years). Vaccination effect was calculated as the percentage change in incidence ratios between pre- and post-vaccination periods. The ratio of COVID-19 cases in those aged ≥50 years to those aged <50 years decreased significantly after vaccine implementation by 9.8% (95% CI: 9.5 to 10.1%) in Chile, 22.5% (95% CI: 22.0 to 23.1%) in Colombia, 20.8% (95% CI: 20.6 to 21.1%) in Guatemala, and 7.8% (95% CI: 7.6 to 7.9%) in the USA. Reductions in the ratio were highest in adults aged ≥70 years. The effect of vaccination on deaths, with time lags incorporated, was highest in the age group ≥70 years in both Chile and Guatemala: 14.4% (95% CI: 11.4 to 17.4%) and 37.3% (95% CI: 30.9 to 43.7%), respectively. COVID-19 vaccination significantly reduced morbidity in the early post-vaccination period in targeted groups. In the context of a global pandemic with limited vaccine availability, prioritization strategies are important to reduce the burden of disease in high-risk age groups.

An assessment of intervention thresholds for high fracture risk in Chile.

The aim of the present study was to explore treatment paths and characteristics of women eligible for treatment in Chile based on major osteoporotic fracture (MOF) probabilities derived from FRAX®. Intervention and assessment thresholds were derived using methods adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Chile. Age-dependent and hybrid assessment and intervention thresholds were applied to 1998 women and 1122 men age 50years or more drawn from participants in the National Health Survey 2016-2017. Approximately 12% of men and women had a prior fragility fracture and would be eligible for treatment for this reason. Using age-dependent thresholds, an additional 2.6% of women (0.3% of men) were eligible for treatment in that MOF probabilities lay above the upper assessment threshold. A BMD test would be recommended in 5% of men and 38% of women. With hybrid thresholds, an additional 13% of women (3.6% of men) were eligible for treatment and BMD recommended in 11% of men and 42% of women. The application of hybrid intervention thresholds ameliorates the disparity in fracture probabilities seen with age-dependent thresholds. Probability-based assessment of fracture risk, including the use of the hybrid intervention thresholds for Chile, is expected to help guide decisions about treatment.

The Epidemiology of Violent Deaths in Chile between 2001 and 2018: Prevalence, Trends, and Correlates.

Background: Despite its enormous health and social burden, there are limited published studies describing the epidemiology of violent deaths in Chile. We described violent mortality rate trends in Chile between 2001 and 2018, its current spatial distribution and ecological level correlates. Methods: A population-based study using publicly accessible data. We calculated age-adjusted mortality rates per 100,000 persons for sex, age, intention, and mechanism of death. Next, we used linear regression to estimate time trends for sex and intention. We then employed hierarchical Poisson analyses to model the spatial distribution across 345 municipalities and the influence of six ecological level variables. Results: The average rate of violent death in Chile between 2001 and 2018 was 15.9 per 100,000 people, with the majority (70.3%) of these attributed to suicide. Suffocation was the most common mechanism of death for suicide (82.3%) and cut/pierce for homicide (43.1%), followed by firearm (33.2%). Violent deaths are trending downward in Chile across all categories except suicides by women, which have remained stable. Poverty rates and urban population were positively associated with violent mortality rates. Conclusions: Although violence-related deaths seem to be decreasing, disparities across gender, age group, and geographic location may have continuing effects on mortality rates.

A registry of out-of-hospital cardiac arrest in Chile

The rate of survival to hospital discharge is less than 10% for out-of-hospital cardiac arrest (OHCA). To develop and implement a Chilean prospective, standardized cardiac arrest registry following the Utstein criteria. We conducted a prospective registry for patients presenting at an urban, academic, high complexity emergency department (ED) after having an OHCA. The facility serves approximately 10% of the national population. Data were registered and analyzed following the Utstein criteria for reporting OHCA. For three years, 289 patients aged 59 ± 19 years (63% men) were included. Fifty seven percent of patients were taken to a health care facility for the first medical assessment by relatives or witnesses and 34% was assisted and transferred by prehospital personnel. In the subgroup of non-traumatic OHCA, 28% (n = 54) received bystander cardiopulmonary resuscitation (CPR). The registered cardiac rhythms were asystole (61%), pulseless electrical activity (PEA) (25%) and ventricular tachycardia (VT) or ventricular fibrillation (VF) (11%). The overall survival rate to discharge from the hospital was 10%, while survival with mRankin score 0-1 was 5%. The median hospitalization length of stay was 18 days among those who survived, compared with five days for the group of patients that died during the hospital stay. OHCA is an important cause of death in Chile. The development of a national registry that follows the International Liaison Committee on Resuscitation guidelines is the first step to assess the profile of OHCA in the region. It will provide crucial information to identify prognostic factors and variables that can help develop standards of care and set up the basis to optimize cardiac arrest management within our country and region.

Chile's public healthcare sector hypertension control rates before and during the pandemic and HEARTS implementation.

ABSTRACTHypertension (arterial blood pressure ≥ 140/90 mmHg) is a risk factor for cardiovascular diseases, with the greatest burden of attributable deaths in Chile, having a national prevalence of 27.6%. In 2018, the implementation of HEARTS begun in primary health care centers of the Public Health System, with the aim of achieving increase in control rates, by raising the proportion of hypertensive individuals who meet blood pressure goals (< 140/90 mmHg for individuals 15–79 years old and of 150/90 mmHg for individuals 80 years and older), and thus contributing to reduce cardiovascular morbidity and mortality associated with this condition. This is a descriptive study that follows average treatment and control rates from the Public Health System between 2017–2021 obtained from health centers statistics reports during HEARTS implementation. Treatment and control rates remained at 57% and 39% respectively between 2017-2019. Between 2020 and 2021, in the context of the SARS-CoV-2 pandemic, treatment and control rates decreased very significantly, reaching 46% and 26%, respectively, in December 2021, even though the number of centers reporting the implementation of HEARTS increased from 227 to 387 in this same period. Prior to the pandemic, during the last quarter of 2019, a decrease in cardiovascular health controls was already observed as a result of social protests. In light of the results, the technical pillars of the HEARTS Initiative have an important role in helping to recover the population control rates reached in 2019 and increasing the speed to achieve better hypertension control rates.

Beyond death in Chile

Beyond death in Chile

The Role of Leadership in Disaster Management

This paper analyzed leadership practices before and after a mining explosion resulted in twenty nine deaths in Chile. When the first reports came upon the explosion, it appeared that there was a lack of appropriate safety precautions. However, further investigation revealed that the organizational culture created by the leadership was considered as the root cause which could have been prevented if the leadership had established an employee-centric culture. It is possible to see the repercussions of the leadership practices to a great extent. Showing workers that the organization will always do the right thing to assure their safety is an important step toward establishing trust. The despotic leadership, that constantly imposed fear on its employees to discourage them from voicing their opinions and questioning the existing conditions, eventually brought organizational deviance. Members of the organization neither had any meaningful communication nor appropriate information exchange. The absence of mutual trust and respect in the work environment was apparent. This paper sheds further light on the impact of leadership in the prevention of future catastrophic events while ensuring safety and enhanced performance.

Place of death of people with cancer in 12 Latin American countries: a total population study using national death registers

Cancer is the second leading cause of death in almost all Latin American countries. Knowing where people with cancer die and understanding the factors that affect where they die are public health issues, relevant for the development of policies that ensure the provision of adequate end-of-life care in alignment with patients' needs and preferences. The objective of this study was to describe and compare the place of death of people with cancer in 12 Latin American countries, and explore associated factors. We conducted a total population observational study using death certificate data from 12 countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, Mexico, Paraguay, Peru, and Uruguay). Data from individuals deceased during the most recent full year (Jan 1 to Dec 31) with available data (2016, 2017, or 2018) were included. Place of death was categorised as home, hospital, or other places. The sociodemographic factors, cause of death (10th revision of the International Statistical Classification of Diseases and Related Health Problem cancer codes C00-C97 vs others), and ecological factors were estimated, and a multivariable binary logistic regression analysis with the dependent variable home death versus hospital death was done. 3 001 640 deaths were included, of which 491 929 (16·4%) were caused by cancer, ranging from 3161 (8·7%) of 36 441 deaths in El Salvador to 26 027 (33·4%%) of 77 999 deaths in Chile. 1808 (57·2%) of 3161 cancer deaths in El Salvador were in women, a rate that decreased to 3591 (45·5%) of 7884 deaths in Uruguay, but that remained above 50% in half of the included countries (Colombia, Ecuador, El Salvador, Guatemala, Mexico, and Peru). In all countries, 199 900 (40·7%) of 491 574 patients with cancer died before the age of 64 years. Between 32 513 (14·9%) of 217 697 (in Brazil) and 6216 (80·3%) of 7738 (in Guatemala) cancer deaths occurred at home; whereas 175 464 (80·6%) of 217 697 (in Brazil) and 1033 (13·3%) of 7738 (in Guatemala) cancer deaths occurred in hospital. The odds ratios for death at home for people with cancer aged 50-79 years was 1·6 (95% CI 1·6-1·7; p<0·001) and 3·0 (2·9-3·0; p<0·001) for people aged 80 years and older, comparing with those younger than 50 years. Factors affecting place of death patterns in Latin America are country-specific. A high percentage of people dying at home does not necessarily suggest a good palliative care provision, especially in countries with poor palliative care programmes. The health facilities available in each country might explain the variations in the number of places where people die. These findings show current needs and can help to guide different policies to improve end-of-life care for patients with cancer. None.

EE483 The Economic Impact of Coronavirus Pandemic on Stroke Care: Direct and Indirect Costs Estimations in Chile

EE483 The Economic Impact of Coronavirus Pandemic on Stroke Care: Direct and Indirect Costs Estimations in Chile

Abstract 5899: CDH1 and CTNNA1 variants with incomplete penetrance in hereditary gastric cancer Chilean families

Abstract The purpose of this study is to describe two Chilean families having Hereditary Gastric Cancer (GC). Both families present variants of uncertain significance (VUS), that could be pathogenic, but show incomplete penetrance. GC is the leading cause of cancer-related death in Chile. Worldwide, about ten percent of gastric cancer have a familial aggregation and in Hereditary Diffuse Gastric Cancer (HDGC), E-Cadherine 1 gene (CDH1) and alpha-E-catenin gene (CTNNA1) are the most commonly mutated genes. To our knowledge, only one HDGC Chilean family with a pathogenic CDH1 mutation has been reported, suggesting a low frequency of CDH1 mutations in this population. The index patient of the first family had a diffuse GC at age 59-y. His father and paternal grandfather also died of GC. A CDH1 germline variant c.88C&amp;gt;A in (p.Pro30Thr, rs139866691) was found previously in the index patient by Sanger sequencing. Variant genotyping in available family members showed that two non-affected sisters were carriers. In the second family, there were eleven members affected with GC and two with breast cancer. The index patient was diagnosed with a tubular/intestinal gastric tumor at 51y of age and had a brother who died of GC at 38y. Cancer gene panel sequencing was performed in index patient DNA and cascade genotyping in family members was performed using Kompetitive allele-specific PCR. A germline variant c.293G&amp;gt;A (p.R98Q, rs746832629) in the CTNNA1 gene was found in the index patient. We searched the variant in other members of the family and carried out a co-segregation analysis, that indicates an incomplete penetrance of the variant because two non-affected brothers do have it. Additionally, one affected sister did not carry the variant, but her tumor sample´s histology is papillary, the most frequent type in sporadic CG and her age of onset was 60-y. Both rs139866691 and rs746832629 are located in conserved structures of their coding proteins. rs139866691 maps to a conserved loop in the E-Cadherin 1 preprotein domain and rs746832629 maps to the first alpha-helix of alpha-E-catenin corresponding to the beta-catenin binding domain. Based on our data, we believe that both variants are likely pathogenic and causative of the hereditary GC observed in these families but show incomplete penetrance. To search for additional candidate pathogenic variants, we recently completed whole-exome sequencing in the index cases from the two available affected cases of the second family and we found other candidate genes reported in breast cancer and related with nitroso compound metabolism. We are searching for the second hit in the second family index patient´s tumor sample and performing isogenic models and functional analysis of rs139866691 and rs746832629 to clarify their pathogenicity. Citation Format: Graciela Molina, Carol Parra, Nicole B Halmai, Ana P Estrada, Alma Poceros, Paul Lott, Rasika Venkatesh, Enrique Norero, Osvaldo Torres, Alejandro Corvalán, Luis Carvajal-Carmona. CDH1 and CTNNA1 variants with incomplete penetrance in hereditary gastric cancer Chilean families [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5899.

Abstract 1969: Distinctive profiles on immunotherapy responders versus non responders in Chilean gastric cancer patients

Abstract Background: Gastric cancer (GC) is the leading cause of cancer death in Chile, claiming &amp;gt;3,000 lives per year. On April 2021, the US Food and Drug Administration approved the combined use of Nivolumab (immunotherapy) plus chemotherapy as frontline treatment for advanced GC. Unfortunately, as occurs with any therapy, a proportion of treated patients are either unresponsive or display poor responses. Our study sought to obtain a profile of GC patients categorized as responders or non-responders to immunotherapy in order to identify better predictors of response and novel targets for treatment refractory patients. Methods: A total of 50 GC patients were included into our study. Demographic and basic information was obtained from medical records. Additionally, we retrieved information on response to treatment, histological type, PDL1 and HER2 status. Nucleic acid samples were collected from a subset of 45 patients (responders and non-responders) and analyzed by massive analysis of cDNA ends (MACE-seq) assessing 3’ mRNA sequencing. Results: Patients were predominantly male (76%) and advanced stage (III/IV; 98%). Within this subset, 26 were responders and 24 were non-responders. Among clinical variables, body mass index was significantly higher on responders versus non-responders (p=0.026). Among responders, tumors were predominantly located on the gastro-esophagic junction. As expected, responders also displayed a higher prevalence of HER2- and PDL1+. Our 3’ MACE analysis confirmed distinct profiles on responders compared to non-responders. Conclusions: Our findings confirm distinctive profiles among Chilean GC patients categorized as responders or non-responders to immunotherapy. These results could deliver novel markers that may serve as predictors of response to immunotherapy (as an alternative to PDL1) or to identify patients more likely to be refractory to treatment. Future studies should further confirm and validate these findings in a larger sample. Citation Format: Mauricio P. Pinto, Matias Muñoz Medel, Miguel Córdova Delgado, Ignacio N. Retamal, Patricio Manque, Alejandro Berkovits, Maria Paz Rodriguez, Juvenal A. Rios, Benjamin Garcia-Bloj, Gareth Owen, Marcelo Garrido. Distinctive profiles on immunotherapy responders versus non responders in Chilean gastric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1969.

Mortality due to endemic and imported parasitoses in Chile. 1997-2020

Parasites are a public health problem due to their high prevalence in developing countries, their persistence in developed countries mainly due to the migration of people, and their associated morbidity and mortality. To determine the deaths in Chile caused by endemic and imported parasites; according to region, sex, age group, urban-rural origin and educational level, and mortality rates. Population-based study, times series of mortality (1997 to 2020). Statistical analysis was performed using Excel and R Studio programs, calculation of χ2, p value < 0.05. 2,413 deaths occurred due to parasites, 65.1% by protozoa, 33% by helminths and 1.9% by arthropods. The average national mortality rate was 0.6 per 100.000 inhabitants. The main causes of death were Chagas disease (63.6%), hydatidosis (24.3%) and cysticercosis (8.1%). Most of the deceased belonged to the Coquimbo Region. The mean age of death was 74, 62 and 67 years old for deaths from protozoa, helminths and arthropods, respectively. Deaths occurred mostly in men. Most came from urban areas and had a low educational level. Chagas disease is the main cause of death from parasites in Chile.

Changes in cardiovascular mortality in Chile during the COVID-19 pandemic

ObjectivesThe COVID-19 pandemic has impacted regular cardiovascular healthcare access and delivery. Service utilisation has declined, and excess cardiovascular mortality has been reported in several countries. We aim to estimate excess...

Single Nucleotide Polymorphisms in Apolipoprotein B, Apolipoprotein E, and Methylenetetrahydrofolate Reductase Are Associated With Serum Lipid Levels in Northern Chilean Subjects. A Pilot Study.

Characterization of allelic variants is relevant to demonstrate associations among genetic background and susceptibility to develop cardiovascular diseases, which are the main cause of death in Chile. Association of APOB, APOE, and MTHFR polymorphisms with higher lipid levels and the risk of developing hypertension and cardiovascular diseases have been described. Thus, the aim of this study was to assess genotype distribution and relative allelic frequency of ApoB rs693, ApoE rs7412, ApoE rs429358, MTHFR rs1801131, and MTHFR rs1801133 allelic variants and their effects on lipid profile in young healthy men and women from Northern Chile. A group of 193 healthy subjects were enrolled for this study. Genotyping of rs693 (APOB), rs7412 and rs429358 (APOE), and rs1801131 and rs1801133 (MTHFR) polymorphisms were performed by real time PCR. In addition, lipid profiles were determined and associated to genetic data. The genotype distribution was APOB rs693 (CC = 37%, CT = 41%, and TT = 22%), APOE rs7412/rs429358 (E4 = 0.06, E3 = 0.91, and E2 = 0.03), MTHFR rs1801131 (AA = 57%, AC = 30%, and CC = 13%), and MTHFR rs1801133 (CC = 20%, CT = 47%, and TT = 33%). The association of the genetic variants with plasma lipid levels showed that women, but not men, carrying APOB mutated allele (T) and Apo E4 allele presented lower values of total cholesterol when compared with C/C homozygous genotype or E3 allele, respectively (p < 0.05). In addition, a subgroup analysis revealed that ApoB C/C homozygous women exhibited higher values of HDL-C when compared with men carrying identical genotype (p < 0.01). On the other hand, women carrying E4 allele exhibited lower values of triglycerides when compared with male carrying identical genotype (p < 0.05). Finally, women carrying mutate allele (C) for MTHFR rs1801131 showed lower levels of triglycerides when compared with A/A homozygous genotype (p < 0.05) and lower levels of LDL-C for MTHFR rs1801133 in females carrying (T) allele when compared with males carrying identical genotype (p < 0.05). In summary, the present data showed that APOB, APOE, and MTHFR single nucleotide polymorphisms are associated to lipid levels in a gender-dependent manner among healthy subjects from Northern Chile, especially in women.

Abstract 800: A germline CTNNA1 variant in a large Chilean family with hereditary diffuse gastric cancer

Abstract The purpose of this study is to describe a large Chilean family having a Hereditary Diffuse Gastric Cancer and a possible causative mutation of cancer in this family. Gastric cancer is the leading cause of cancer-related death in Chile. Worldwide, only ten percent of gastric cancer have a familial aggregation and in Hereditary Diffuse Gastric Cancer (HDGC), E-Cadherine 1 gene (CDH1) is the most commonly mutated gene (30%). To our knowledge, only one HDGC Chilean family with a pathogenic CDH1 mutation has been reported, suggesting a low frequency of CDH1 mutations in this population. CTNNA1 mutations (alpha-1 catenin gene), also have been found in HDGC cases. E-cadherine 1 and alpha-1 catenin are part of adherens junction complex. In this family, there are eleven members affected with gastric cancer and two with breast cancer, in two following generations. The index patient was diagnosed with a diffuse gastric tumor at 51 years of age and one affected relative (a deceased brother of the index case) at 38 years of age. The index patient´s gastric tumor histology type is diffuse, but the tumor of the affected sister is papillary. Cancer gene panel sequencing was performed in index patient DNA and cascade genotyping in family members was performed using Kompetitive allele-specific PCR. A germline variant c.293G&amp;gt;A (p.R98Q, rs746832629) in the CTNNA1 gene was found in the index patient. This variant has been reported two times in ClinVar and is classified as an uncertain significance variant. In TCGA, CTNNA1 c.293G&amp;gt;A variant has been reported four times in gastric, colon, and uterine tumor samples. This variant maps to the beta-catenin binding domain of the protein, and the mutated residue is conserved from fish to primates. The variant population frequency in the Genome Aggregation Database is in Latinos is 0.0049 and worldwide is 0.000076. We searched the variant in other members of the family and carried out a co-segregation analysis, that indicates an incomplete penetrance of the variant because two non-affected brothers do have it. Based on our data, we think that this variant could be pathogenic and causative of the HDGC observed in this family, but showing an incomplete penetrance. Additionally, the variant was not found in sixty-two other early-onset Chilean cancer gastric patients, thus we are going to search the variant in a sample of the general population of the family´s region. Also, we will do a whole-exome sequence in the samples of all available affected relatives looking for other variants to explain the incomplete penetrance, search for the second hit in an index patient´s tumor sample and perform a functional analysis of the variant during this semester. Beca Chile Postdoctorado 74190063, CONICYT-FONDAP 15130011-2 (NIH). Citation Format: Graciela Molina, Ana Estrada, Alma Poceros, Carol Parra, Osvaldo Torres, Natalia Landeros, Andrés Rodríguez, Alejandro Corvalán, Luis Carvajal-Carmona. A germline CTNNA1 variant in a large Chilean family with hereditary diffuse gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 800.

Perioperative chemotherapy in locally advanced gastric cancer in Chile: from evidence to daily practice.

Gastric cancer (GC) is a leading cause of cancer death in Chile. Although recommended in international guidelines since 2006, perioperative chemotherapy was not available to patients in the public health system in Chile until 2016. We conducted an observational study to assess the feasibility of this strategy in public hospitals in Chile (Observational Study of Perioperative Chemotherapy in Locally Advanced Gastric Cancer – PRECISO). Patients with locally advanced, operable GC were offered to receive preoperative chemotherapy with Epirubicin + Cisplatin + Capecitabine (ECX) for three cycles followed by curative surgery. Staging included abdominal CT scan and laparoscopy if peritoneal carcinomatosis was suspected. Postoperative ECX for three cycles was recommended. Between August 2010 and March 2013, 110 patients were screened and 61 enrolled. Median age was 62 years (23–76 years) and most patients had good performance status at baseline (Eastern Cooperative Oncology Group performance status score (ECOG) 0: 42, ECOG 1: 19). Tumour site was proximal in 32 (52%) and medial and distal in 29 (48%) patients. All but four patients (n = 57, 93%) completed three cycles of preoperative chemotherapy. Fifty-six patients were operated and 54 (89%) had a curative resection. Thirty-three patients (54%) had pT0-2, and 18 (30%) had pN0 tumours, with two patients achieving a complete response. As of 20 December 2020, 39 patients died, 32 due to GC, one within 30 days of surgery, two due to intestinal obstruction at 5 and 3 months after surgery and four due to other causes. Five-year survival rate was 38%. We conclude that perioperative chemotherapy is feasible in public hospitals in Chile and should be offered to patients with locally advanced GC.