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Abstract Background In Colombia and worldwide, breast cancer (BC) is the most frequently diagnosed neoplasia and the leading cause of death from cancer among women. Studies predominantly involve hereditary and familial cases, demonstrating a gap in the literature regarding the identification of germline mutations in unselected patients from Latin-America. Identification of pathogenic/likely pathogenic (P/LP) variants is important for shaping national genetic analysis policies, genetic counseling, and early detection strategies. The present study included 400 women with unselected breast cancer (BC), in whom we analyzed ten genes, using Whole Exome Sequencing (WES), know to confer risk for BC, with the aim of determining the genomic profile of previously unreported P/LP variants in the affected population. Additionally, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to identify Large Genomic Rearrangements (LGRs) in the BRCA1/2 genes. To ascertain the functional impact of a recurrent intronic variant (ATM c.5496 + 2_5496 + 5delTAAG), a minigene assay was conducted. Results We ascertained the frequency of P/LP germline variants in BRCA2 (2.5%), ATM (1.25%), BRCA1 (0.75%), PALB2 (0.50%), CHEK2 (0.50%), BARD1 (0.25%), and RAD51D (0.25%) genes in the population of study. P/LP variants account for 6% of the total population analyzed. No LGRs were detected in our study. We identified 1.75% of recurrent variants in BRCA2 and ATM genes. One of them corresponds to the ATM c.5496 + 2_5496 + 5delTAAG. Functional validation of this variant demonstrated a splicing alteration probably modifying the Pincer domain and subsequent protein structure. Conclusion This study described for the first time the genomic profile of ten risk genes in Colombian women with unselected BC. Our findings underscore the significance of population-based research, advocating the consideration of molecular testing in all women with cancer.

PURPOSEBreast cancer (BC) is the most frequent neoplasm in women in Colombia and is associated with a higher mortality rate than in other countries and regions. Neoadjuvant chemotherapy (NACT) has become a standard treatment in locally advanced BC and provides an opportunity to improve clinical outcomes in BC. This study aims to describe characteristics, treatment patterns, and outcomes after NACT in a cohort of Colombian patients with BC.METHODSWe performed a retrospective cohort study. We included adult patients with BC treated with NACT. Clinical charts were retrospectively reviewed. Descriptive statistics and time to event for overall survival analyses were performed. Recursive partitioning was performed for survival curves to assess the complex relationship between survival times and other variables.RESULTSThree hundred and fourteen patients were included for analysis. The pathologic complete response after neoadjuvant chemotherapy (ypCR) rate was 34.4%, with a higher ypCR in triple-negative BC (TNBC; 46.9%) and human epidermal growth factor receptor 2–positive BC (72.7%). Those who did not achieve ypCR had a higher percentage of death and relapse. The median follow-up was 4.9 years, with an 88.2% 5-year overall survival (OS).CONCLUSIONA total of 62.6% of the total patients identified were not treated with NACT, indicating a low utilization. Our global ypCR rate was higher when compared with similar studies in Colombia, likely because of differences in the NACT treatment regimens. ypCR was only associated with OS in the TNBC subgroup, emphasizing the importance of pursuing ypCR in these patients. We consider the use of NACT a valuable opportunity to implement innovative treatment approaches that improve outcomes in Colombian patients with BC.

Abstract Background Measurement of the optic nerve sheath diameter (ONSD) provides a rapid, safe, and easy method for detecting increased intracranial pressure (ICP). However, the normal mean and upper limit values may vary according to sex, age, ethnicity, and ultrasound technique. Aim We aimed to obtain the mean ONSD in a healthy Colombian adult population and to correlate it with demographic and anthropometric measures. Methods In a prospective study using a 10–13 MHz linear ultrasound probe, eye transverse diameter (ETD) and ONSD in the transverse (ONSD-TP) and sagittal planes (ONSD-SP) were measured in healthy adult volunteers in Bogota, Colombia. Results A total of 100 healthy subjects were included, with a mean age of 26,7 ± 8,3 years and 62 women. The mean ETD, ONSD-TP and ONSD-SP was 23.11 mm (95% confidence interval (CI): 22.90 mm-23.32 mm), 3.96 mm (95% CI: 3.85 mm-4.07 mm) and 4.0 mm (95% CI: 3.90 mm-4.11 mm), respectively. The ONSD in both planes ranged from 2.35 mm to 5.20 mm. There was a significant correlation between ONSD-SP and ONSD-TP (p 0.05). The intraclass correlation between the eyes was statistically significant. Conclusion Our study shows that ultrasound-measured ONSD in healthy adults in Colombia is similar to that found worldwide. An ONSD of 5.5 mm may be considered the upper limit for healthy adults in Colombia. ONSD can be measured in either plane; there is a good correlation between the two eyes; and ONSD is not modified by demographic or anthropometric characteristics.

Objective. Rheumatoid arthritis (RA) is the most common autoimmune arthropathy worldwide. The increased prevalence of cardiovascular disease (CVD) in RA is not fully explained by classic risk factors. The aim of this study was to determine the influence of rs1058587 SNP within GDF15(MIC1) gene on the risk of CVD in a Colombian RA population. Methods. This was a cross-sectional analytical study in which 310 consecutive Colombian patients with RA and 228 age- and sex-matched controls were included and assessed for variables associated with CVD. The mixed cluster methodology based on multivariate descriptive methods such as principal components analysis and multiple correspondence analyses and regression tree (CART) predictive model were performed. Results. Of the 310 patients, 87.4% were women and CVD was reported in 69.5%. Significant differences concerning GDF15 polymorphism were not observed between patients and controls. Mean arterial pressure, current smoking, and some clusters were significantly associated with CVD. Conclusion. GDF15 (rs1058587) does not influence the development of CVD in the population studied.

Abstract Background There are few data on the clinical outcomes of patients with coronavirus disease 2019 (COVID-19) in cities over 1000 m above sea level (masl). Objectives To describe the clinical characteristics and mortality of patients with COVID-19 treated at a high complexity hospital in Bogotá, Colombia, at 2640 masl. Methods This was an observational study of a cohort including 5161 patients with confirmed COVID-19 infection from 19 March 2020 to 30 April 2021. Demographic data, laboratory values, comorbidities, oxygenation indices, and clinical outcomes were collected. Data were compared between survivors and nonsurvivors. An independent predictive model was performed for mortality and invasive mechanical ventilation (IMV) using classification and regression trees (CART). Results The median cohort age was 66 years (interquartile range (IQR) 53–77), with 1305 patients dying (25%) and 3856 surviving (75%). The intensive care unit (ICU) received 1223 patients (24%). Of 898 patients who received IMV, 613 (68%) of them perished. The ratio of partial pressure arterial oxygen (PaO2) to fraction inspired oxygen (FiO2), or the P/F ratio, upon ICU admission was 105 (IQR 77–146) and 137 (IQR 91–199) in the deceased and survivors, respectively. The CART model showed that the need for IMV, age greater than 79 years, ratio of oxygen saturation (SaO2) to FiO2, or the S/F ratio, less than 259, and lactate dehydrogenase (LDH) greater than 617 U/L at admission were associated with a greater probability of death. Conclusion Among more than 5000 patients with COVID-19 treated in our hospital, mortality at hospital discharge was 25%. Older age, low S/F ratio, and high LDH at admission were predictors of mortality.

ABSTRACT: Objectives: This study aimed to explore associations between the molecular characterization of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and disease severity in ambulatory and hospitalized patients in two main Colombian epicentres during the first year of the coronavirus disease 2019 pandemic. Methods: In total, 1000 patients with SARS-CoV-2 infection were included in this study. Clinical data were collected from 997 patients, and 678 whole-genome sequences were obtained by massively parallel sequencing. Bivariate, multi-variate, and classification and regression tree analyses were run between clinical and genomic variables. Results: Age >88 years, and infection with lineages B.1.1, B.1.1.388, B.1.523 or B.1.621 for patients aged 71–88 years were associated with death [odds ratio (OR) 6.048036, 95% confidence interval (CI) 1.346567–32.92521; P=0.01718674]. The need for hospitalization was associated with higher age and comorbidities. The hospitalization rate increased significantly for patients aged 38–51 years infected with lineages A, B, B.1.1.388, B.1.1.434, B.1.153, B.1.36.10, B.1.411, B.1.471, B.1.558 or B.1.621 (OR 8.368427, 95% CI 2.573145–39.10672, P=0.00012). Associations between clades and clinical outcomes diverged from previously reported data. Conclusions: Infection with lineage B.1.621 increased the hospitalization and mortality rates. These findings, plus the rapidly increasing prevalence in Colombia and other countries, suggest that lineage B.1.621 should be considered as a ‘variant of interest’. If associated disease severity is confirmed, possible designation as a ‘variant of concern’ should be considered.

En el presente artículo se presenta una revisión de los principales resultados del proyecto RAIZ, acrónimo de “Respuesta autoinmune en individuos infectados por el virus Zika”, originado por dos eventos mutuamente relacionados, la asociación entre un virus emergente en el continente, el virus Zika (vZika), y una enfermedad neuromuscular poco prevalente en Colombia, el síndrome de Guillain-Barré. Después de la llegada del virus al país se observó que las zonas donde se reportaban brotes del virus, se documentaba un aumento en los casos de síndrome de Guillain-Barré y otros síndromes neurológicos, que generó un gran interés para entender los mecanismos subyacentes de la infección asociados con autoinmunidad neurológica. Mediante la realización del primer estudio de casos y controles de Zika, Guillain-Barré y otros síndromes neurológicos, se comprobó dicha asociación en Colombia. A lo largo del proyecto, además, se investigaron los principales mecanismos asociados, mediante estudios de seroprevalencia de otras infecciones, inmunológicos y genéticos

Abstract Background Evidence supports the existence of different subphenotypes in systemic lupus erythematosus (SLE) and the pivotal role of cytokines and autoantibodies, which interact in a highly complex network. Thus, understanding how these complex nonlinear processes are connected and observed in real-life settings is a major challenge. Cluster approaches may assist in the identification of these subphenotypes, which represent such a phenomenon, and may contribute to the development of personalized medicine. Therefore, the relationship between autoantibody and cytokine clusters in SLE was analyzed. Methods This was an exploratory study in which 67 consecutive women with established SLE were assessed. Clinical characteristics including disease activity, a 14-autoantibody profile, and a panel of 15 serum cytokines were measured simultaneously. Mixed-cluster methodology and bivariate analyses were used to define autoantibody and cytokine clusters and to identify associations between them and related variables. Results First, three clusters of autoantibodies were defined: (1) neutral, (2) antiphospholipid antibodies (APLA)-dominant, and (3) anti-dsDNA/ENA-dominant. Second, eight cytokines showed levels above the threshold thus making possible to find 4 clusters: (1) neutral, (2) chemotactic, (3) G-CSF dominant, and (4) IFNα/Pro-inflammatory. Furthermore, the disease activity was associated with cytokine clusters, which, in turn, were associated with autoantibody clusters. Finally, when all biomarkers were included, three clusters were found: (1) neutral, (2) chemotactic/APLA, and (3) IFN/dsDNA, which were also associated with disease activity. Conclusion These results support the existence of three SLE cytokine-autoantibody driven subphenotypes. They encourage the practice of personalized medicine, and support proof-of-concept studies.

Objectives: To assess the effectiveness, safety, and drug survival of subcutaneous (SC) abatacept (ABA) in a cohort of rheumatoid arthritis (RA) patients in a real-world setting. Methods: This was a retrospective cohort study from 2014 to 2018 in which patients with RA (1987 ACR criteria) were included. Patients were evaluated at a single rheumatology outpatient center in Bogotá, Colombia. The patients were classified according to their treatment background: biological-naïve (n = 65), switched from IV to SC ABA administration (125 mg-wk) (n = 32), and inadequate response to biological DMARD (n = 62). The primary endpoint was a change in DAS28-CRP and RAPID3 from baseline to 12 months. A linear mixed effect model was used to correlate repeated measures. Adverse events were assessed and recorded during each visit to the rheumatology center. Several Cox proportional hazard regression models were used to test if there were any differences in drug survival curves based on seropositivity for rheumatoid factor (RF), and anti-Cyclic Citrullinated Peptide Antibodies (anti-CCP). Statistical analysis was done using software R version 3.4.4. Results: A total of 159 patients were included. Baseline characteristics of patients were as follows: female gender 84%, median age of 54 years (IQR 16), median disease duration 10 years (11), RF positive 96%, anti-CCP positive 89%, erosive disease 55%, median DAS28-CRP 5.0 (2), and median RAPID3 17 (10). Concomitant use of methotrexate and SC ABA monotherapy were reported at 52% and 30% respectively. Demographics and disease characteristics were similar for all groups, except for baseline DAS28-CRP, and RAPID3 in the group that switched route of administration. The interaction between time and group was significant (p = 0.0073) for RAPID3. Infections, constitutional symptoms, and headaches were the most frequent AEs. Retention rate corresponded to 60% at 48 months. The most frequent reason for drug suspension was loss of efficacy. Median time of treatment for SC ABA was 31 months (IQR 30). The only association that reached statistical significance was anti-CCP concentration [Q1–Q4] (p = 0.005). According to the Cox proportional hazard regression model, there were significant differences between survival curves for Q1 (HR 0.15; 0.03–0.64 95% CI; p = 0.0096), and Q2 (HR 0.28; 0.08–0.92 95% CI; p = 0.0363) compared to the seronegative group. Conclusions: The results showed an improvement in RA disease activity and physical function in patients under SC ABA treatment. Patients switching from IV to SC administration of ABA had lower activity and functional impairment at baseline. SC ABA demonstrated a good safety profile consistent with previously published data. Patients with baseline levels of anti-CCP antibody concentrations had better drug survival than seronegative patients. Keywords: Rheumatoid arthritis, Subcutaneous abatacept, Latin America, Real world data, Precision medicine

BACKGROUND:Observational studies have indicated a high but heterogeneous prevalence of low bone mineral density (BMD) and vertebral fractures (VF) in patients with systemic lupus erythematosus (SLE). Therefore, the objectives of this systematic review and meta-regression were: 1) to compare BMD between SLE patients and healthy controls and 2) to evaluate the relationship between BMD and glucocorticoid therapy and VF in SLE patients. METHODS AND FINDINGS:Articles were identified from electronic databases (PubMed, Embase, VHL, SciELO and the Cochrane Library). Prospective longitudinal and cross-sectional studies were considered for review. We evaluated the quality of the evidence included using the Oxford Centre for evidence-based medicine (EBM) Levels of Evidence. In total, 38 articles were identified and analyzed (3442 SLE cases and 6198 controls) in the analysis of BMD (9232 women and 408 men). There were significant differences in mean BMD between SLE patients and controls. BMD mean difference in cases/controls: -0.0566 95% CI (-0.071, -0.0439; p = < 0.0001). When only SLE patients were analyzed, the BMD did not significantly differ between patients who had or had not received glucocorticoid (GCT) therapy. 694 SLE patients were included in the analysis of VF (189 with VF vs. 505 without VF). Patients with VF had lower BMD than patients without VF (BMD mean difference without VF/with VF: 0.033 (95%CI: 0.006-0.060); p-value: 0.0156). CONCLUSIONS:Patients with SLE had lower BMD than healthy controls. Moreover, SLE patients with VF had lower BMD than patients without VF. However, our data did not show that GCT therapy had an impact on BMD.

Se hizo un análisis estadístico de la tendencia de la precipitación, temperatura media mensual y la razón de aridez anual para el periodo 1973-2011, en Providencia Isla, Colombia. Los dieciséis datos mensuales faltantes se imputaron con un modelo SARIMA. Los resultados sugieren que la precipitación no presenta tendencia, mientras que su varianza inequívocamente está en aumento. La temperatura muestra una pendiente pronunciada hasta 1981 y la prueba de Mann-Kendall exhibe una tendencia positiva y altamente significativa para toda la serie, aunque no según la prueba de Dickey-Fuller. La evidencia de la varianza de temperatura va en aumento. En el caso de la razón de aridez anual, la demostración de tendencia es contradictoria y no se observó efecto alguno de El Niño Southern Oscilation (ENSO).

Introducción: Resiliencia es la habilidad de responder de manera positiva a eventos adversos. Ésta puede ser influenciada por factores como el estrés crónico, la actividad física y afecciones autoinmunes y/o inflamatorias como la esclerosis sistémica (ES) (1). Objetivo: Evaluar un panel de citoquinas y su asociación con resiliencia, severidad de los síntomas y actividad física en pacientes con ES. Métodos: Este fue un estudio exploratorio que incluyó 35 mujeres con ES. Las características clínicas, incluidas la severidad de los síntomas, la actividad física, la resiliencia así como un panel de 15 citoquinas fueron evaluados simultáneamente. Los análisis estadísticos fueron realizados mediante las pruebas de Spearman y Kruskall-Wallis. Resultados: La mediana para la edad, la severidad de los síntomas y la resiliencia fue de 58 (IQR 51.5-62.5), 52 (IQR 30.5-61) y 3.33 (IQR 2.8-3.7) respectivamente. Dos pacientes (5,7%) mostraron subfenotipo difuso y 23 (66%) informaron actividad física en el momento del estudio, es decir, prácticar ejercicio durante 30 minutos y al menos 3 veces por semana. Aunque no hubo un patrón específico de citoquinas asociado con la resiliencia, IL-5, IL-10 e IL-13 la afectaron negativamente. Los niveles de IL-6 se correlacionaron positivamente con la gravedad de los síntomas (rs = 0,4, p = 0,02) y fueron más altos en pacientes con puntajes bajos de resiliencia (Figura 1). Los niveles de citoquinas no difirieron significativamente entre los grupos de acuerdo con la actividad física. Por último, la severidad de los síntomas no afectó la resiliencia. Conclusiones: Estos resultados resaltan la relevancia de IL-5, IL-10 e IL-13 en la resiliencia y, sobretodo, el papel de la IL-6 en la severidad de los síntomas en pacients con ES.

BackgroundCeliac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in susceptible individuals, and its prevalence varies depending on the studied population. Given that information on CD in Latin America is scarce, we aimed to investigate the prevalence of CD in this region of the world through a systematic review and meta-analysis.Methods and findingsThis was a two-phase study. First, a cross-sectional analysis from 981 individuals of the Colombian population was made. Second, a systematic review and meta-regression analysis were performed following the Preferred Reporting Items for Systematic Meta- Analyses (PRISMA) guidelines. Our results disclosed a lack of celiac autoimmunity in the studied Colombian population (i.e., anti-tissue transglutaminase (tTG) and IgA anti-endomysium (EMA)). In the systematic review, 72 studies were considered. The estimated prevalence of CD in Latin Americans ranged between 0.46% and 0.64%. The prevalence of CD in first-degree relatives of CD probands was 5.5%. The coexistence of CD and type 1 diabetes mellitus varied from 4.6% to 8.7%, depending on the diagnosis methods (i.e., autoantibodies and/or biopsies).ConclusionsAlthough CD seems to be a rare condition in Colombians; the general prevalence of the disease in Latin Americans seemingly corresponds to a similar scenario observed in Europeans.

OBJECTIVES: To examine the prevalence and associated factors related to the coexistence of antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) in a cohort of Colombian patients with SLE, and to discuss the coexistence of APS with other autoimmune diseases (ADs). METHOD: A total of 376 patients with SLE were assessed for the presence of the following: 1) confirmed APS; 2) positivity for antiphospholipid (aPL) antibodies without a prior thromboembolic nor obstetric event; and 3) SLE patients without APS nor positivity for aPL antibodies. Comparisons between groups 1 and 3 were evaluated by bivariate and multivariate analysis. RESULTS: Although the prevalence of aPL antibodies was 54%, APS was present in just 9.3% of SLE patients. In our series, besides cardiovascular disease (AOR 3.38, 95% CI 1.11-10.96, p = 0.035), pulmonary involvement (AOR 5.06, 95% CI 1.56-16.74, p = 0.007) and positivity for rheumatoid factor (AOR 4.68, 95%IC 1.63-14.98, p = 0.006) were factors significantly associated with APS-SLE. APS also may coexist with rheumatoid arthritis, Sjögren's syndrome, autoimmune thyroid diseases, systemic sclerosis, systemic vasculitis, dermatopolymyositis, primary biliary cirrhosis and autoimmune hepatitis. CONCLUSIONS: APS is a systemic AD that may coexist with other ADs, the most common being SLE. Awareness of this polyautoimmunity should be addressed promptly to establish strategies for controlling modifiable risk factors in those patients.

Objective. This study was performed to determine the prevalence of and associated risk factors for cardiovascular disease (CVD) in Latin American (LA) patients with systemic lupus erythematosus (SLE). Methods. First, a cross-sectional analytical study was conducted in 310 Colombian patients with SLE in whom CVD was assessed. Associated factors were examined by multivariate regression analyses. Second, a systematic review of the literature on CVD in SLE in LA was performed. Results. There were 133 (36.5%) Colombian SLE patients with CVD. Dyslipidemia, smoking, coffee consumption, and pleural effusion were positively associated with CVD. An independent effect of coffee consumption and cigarette on CVD was found regardless of gender and duration of disease. In the systematic review, 60 articles fulfilling the eligibility criteria were included. A wide range of CVD prevalence was found (4%–79.5%). Several studies reported ancestry, genetic factors, and polyautoimmunity as novel risk factors for such a condition. Conclusions. A high rate of CVD is observed in LA patients with SLE. Awareness of the observed risk factors should encourage preventive population strategies for CVD in patients with SLE aimed at facilitating the suppression of cigarette smoking and coffee consumption as well as at the tight control of dyslipidemia and other modifiable risk factors.