Germline mutations of breast cancer susceptibility genes through expanded genetic analysis in unselected Colombian patients.

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.

Ultrasound measurement of optic nerve sheath diameter in a healthy adult Colombian population.

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 < 0.0001) but no correlation between the ocular measures and demographic or anthropometric variables (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.

Predicting the outcome of initial non-surgical endodontic procedures by periapical status and quality of root canal filling: a cohort study.

To assess the previous periapical status and the quality of root canal filling as predictors of the outcome in initial non-surgical endodontic procedures. A retrospective cohort study was designed in which the presence of a previous periapical lesion was determined radiographically. The quality of the root filling was evaluated in terms of homogeneity, taper, and apical extension. The response variable was dichotomized to success and failure. Bivariate analyzes and a mixed generalized linear model interpreted the association between the explanatory variables and the outcome of the initial non-surgical endodontic procedures. A total of 349 roots were evaluated, and a failure rate of 13.18% was established. Poor filling quality was determined in 8.3% of the roots. As a main result, the presence of a preoperative periapical lesion did not determine a significant risk to the failure of the initial treatment. Unlike, a poor quality of the obturation determined association with an unfavorable outcome like this: (1) homogeneity (OR 2.32; p = 0.0181); (2) taper (OR 5.8; p = 0.0); and, (3) extension (OR 3.41; p = 0.0). Therefore, a significant association between inadequate quality of the root filling and failure of the primary non-surgical endodontic procedures was found. Short length of filling was highly associated with failure. The presence of previous periapical lesion was not found to be a significant predictor for treatment outcomes.

Cluster analysis of autoimmune rheumatic diseases based on autoantibodies. New insights for polyautoimmunity.

Autoimmune diseases (ADs) are a chronic and clinically heterogeneous group of diseases characterized by share common immunopathogenic mechanisms and risk factors (i.e., the autoimmune tautology), which explain the fact that one AD may coexist with others (i.e., polyautoimmunity - PolyA). In the present exploratory study, a mixed-cluster analysis of the most common autoimmune rheumatic diseases (ARDs) was done. A total of 187 consecutive women with established systemic lupus erythematosus (n = 70), rheumatoid arthritis (n = 51), systemic sclerosis (n = 35) and Sjögren's syndrome (n = 31) were included. A comprehensive clinical, autoantibody and cytokine assessment was simultaneously done. Total PolyA was registered in 142 (75.9%) patients. Six clusters were obtained, built mainly on autoantibodies: PolyA-I to -VI. The PolyA-III cluster showed the highest frequency of overt PolyA (p = 0.01), and the PolyA-I, -III, and -IV clusters exhibited the highest positivity for IL-12/23p40 (p = 0.015). These results provide new insights into the pathophysiology of PolyA and warrant prospective validation to enable development of a more accurate taxonomy of ARDs.

Peripheral mitochondrial function correlates with clinical severity in idiopathic Parkinson's disease.

BACKGROUND: Parkinson's disease is an intractable disorder with heterogeneous clinical presentation that may reflect different underlying pathogenic mechanisms. Surrogate indicators of pathogenic processes correlating with clinical measures may assist in better patient stratification. Mitochondrial function, which is impaired in and central to PD pathogenesis, may represent one such surrogate indicator. METHODS: Mitochondrial function was assessed by respirometry experiment in fibroblasts derived from idiopathic patients (n = 47) in normal conditions and in experimental settings that do not permit glycolysis and therefore force energy production through mitochondrial function. Respiratory parameters and clinical measures were correlated with bivariate analysis. Machine-learning-based classification and regression trees were used to classify patients on the basis of biochemical and clinical measures. The effects of mitochondrial respiration on α-synuclein stress were assessed monitoring the protein phosphorylation in permitting versus restrictive glycolysis conditions. RESULTS: Bioenergetic properties in peripheral fibroblasts correlate with clinical measures in idiopathic patients, and the correlation is stronger with predominantly nondopaminergic signs. Bioenergetic analysis under metabolic stress, in which energy is produced solely by mitochondria, shows that patients' fibroblasts can augment respiration, therefore indicating that mitochondrial defects are reversible. Forcing energy production through mitochondria, however, favors α-synuclein stress in different cellular experimental systems. Machine-learning-based classification identified different groups of patients in which increasing disease severity parallels higher mitochondrial respiration. CONCLUSION: The suppression of mitochondrial activity in PD may be an adaptive strategy to cope with concomitant pathogenic factors. Moreover, mitochondrial measures in fibroblasts are potential peripheral biomarkers to follow disease progression. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Cytokine imbalance in patients with systemic sclerosis and resilience: the key role of interleukin-6.

OBJECTIVES: Resilience, the ability to respond positively to adverse events, may be influenced by long-term stressors and autoimmune/inflammatory conditions such as systemic sclerosis (SSc). Since the immune system plays a role in the development of resilience, we aimed to evaluate the relationship between a panel of cytokines and resilience in patients with SSc. METHODS: Thirty-five consecutive women with established SSc were involved in this exploratory study. Clinical characteristics, including severity of symptoms and resilience, a panel of 15 serum cytokines and 17 autoantibodies were assessed simultaneously. Multivariate methods were used to analyse the data. RESULTS: Interleukin-6 (IL-6) levels were associated with severity of symptoms (ß=1.8395, p=0.04), and low resilience scores (ß= -0.581120, p=0.02). Furthermore, resilience was not associated with clinical manifestations nor polyautoimmunity. Cytokine levels did not significantly differ between groups based on regular physical activity. CONCLUSIONS: The results highlight the importance of IL-6 as a key mediator in the altered cytokine network of SSc.

Cytokine and autoantibody clusters interaction in systemic lupus erythematosus.

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.

A comprehensive analysis and immunobiology of autoimmune neurological syndromes during the Zika virus outbreak in Cúcuta, Colombia.

We have focused on the epidemiology and immunobiology of Zika virus (ZIKV) infection and factors associated with the development of Guillain-Barré syndrome (GBS) and other neurological syndromes in Cúcuta, the capital of North Santander department, Colombia. Data of patients with ZIKV disease reported to the national population-based surveillance system were used to calculate the basic reproduction number (R0) and the attack rates (ARs) as well as to develop epidemiological maps. Patients with neurological syndromes were contacted and their diagnoses were confirmed. A case-control study in which 29 patients with GBS associated with ZIKV compared with 74-matched control patients with ZIKV infection alone was undertaken. Antibodies against arboviruses and other infections that may trigger GBS were evaluated. The estimated value of R0 ranged between 2.68 (95% CI 2.54-2.67) to 4.57 (95% CI 4.18-5.01). The sex-specific ARs were 1306 per 100,000 females, and 552 per 100,000 males. A non-linear interaction between age and gender on the ARs was observed. The incidence of GBS in Cúcuta increased 4.41 times secondary to ZIKV infection. The lag time between ZIKV infection and neurological symptoms was 7 days (interquartile range 2-14.5). Patients with GBS appeared to represent a lower socioeconomic status and were living near to environmentally contaminated areas. All GBS patients were positive for IgG antibodies against both ZIKV and Dengue virus, and 69% were positive for Chikungunya virus. Noteworthy, GBS was associated with a previous infection with M. pneumoniae (OR: 3.95; 95% CI 1.44-13.01; p = 0.006). No differences in antibody levels against C. jejuni, Epstein-Barr virus and cytomegalovirus were observed. High rates of cranial nerves involvement and dysautonomia were present in 82% and 75.9%, respectively. Intensive care unit (ICU) admission was necessary in 69% of the GBS patients. Most of the patients disclosed a high disability condition (Hughes grade 4). Dysautonomia was the main risk factor of poor GBS prognosis (i.e., ICU admission and disability). Thirteen patients were diagnosed with other neurological syndromes different to GBS (6 with transverse myelitis, 3 with encephalitis, 3 with peripheral facial palsy and one with thoraco-lumbosacral myelopathy). Our data confirm an increased transmission of ZIKV in Cúcuta, and provide support to the view that severe neurological syndromes are related to ZIKV disease. The complex ways by which previous infections and socioeconomic status interact to increase the risk of GBS in people infected by ZIKV should be further investigated.

Autoimmune thyroid disease in Colombian patients with systemic lupus erythematosus.

OBJECTIVES: To determine the prevalence and the predictive factors of autoimmune hypothyroidism (AH) within a systemic lupus erythematosus (SLE) cohort and to analyse the current information concerning the prevalence and impact of autoimmune thyroid disease (AITD) and thyroid autoimmunity in patients with SLE. METHODS: A total of 376 patients with SLE were assessed for the presence of the following: (i) confirmed AH, (ii) positive thy-roperoxidase/thyroglobulin antibodies [TPOAb/TgAb] without hypothyroidism, (iii) nonautoimmune hypothyroidism and (iv) SLE patients with neither. Multivariate analysis and a classification and regression tree model were used to analyse data. The current information was discussed through a systematic literature review (SLR). RESULTS: In our cohort, the prevalence of confirmed AH was 12%. However, in euthyroid patients with SLE, TPOAb and TgAb were observed in 21% and 10%, respectively. Patients with confirmed AH were significantly older and had later age at onset of the disease. Smoking (adjusted odds ratio (AOR) 6·93, 95% CI 1·98-28·54, P = 0·004), Sjögren's Syndrome (SS) (AOR 23·2, 95% CI 1·89-359·53, P = 0·015) and positivity for anticyclic citrullinated peptide (anti-CCP) (AOR 10·35, 95% CI 1·04-121·26, P = 0·047) were associated with AH-SLE, regardless of gender and duration of the disease. Smoking and SS were confirmed as predictors of AH-SLE. In the SLR, the prevalence of AITD ranged from 1% to 60%. The factors associated with this polyautoimmunity were female gender, older age, smoking, certain autoantibodies, SS, and cutaneous and articular involvement. CONCLUSIONS: AITD is frequent in SLE and does not affect the severity of SLE. Identified risk factors will assist clinicians in the search for AITD. Our results encourage smoke-free policies in patients with SLE.

Temporal gene expression in the hippocampus and peripheral organs to endotoxin-induced systemic inflammatory response in caspase-1-deficient mice.

OBJECTIVES: Caspase-1 (casp1), a key protease involved in the systemic inflammatory response syndrome (SIRS), controls the brain expression of a set of eight genes: Nos2 and Ptgs2 (nitric oxide synthase 2 and prostaglandin-endoperoxide synthase 2, two inducible enzymes), Cxcl1 and Cxcl10 (C-X-C motif chemokine ligand 1 and ligand 10), Tgtp and Gbp2 (T cell-specific GTPase 1 and guanylate-binding protein 2, two GTPases), Adamts1 (a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 1, a metalloprotease) and Il1rn (interleukin-1 receptor antagonist). Our objective was to ascertain whether casp1 also controlled the peripheral expression of these genes and, if so, to compare their central versus peripheral patterns of gene expression in immune and endocrine tissues during SIRS. METHODS: Wild-type (wt) and casp1 knockout (casp1(-/-)) mice were injected with either saline or a high dose of endotoxin/lipopolysaccharide (LPS; 800 µg/mice i.p.). Saline-injected mice were immediately euthanized after injection, whereas LPS-injected mice were sacrificed 6 and 12 h after LPS administration. Hippocampal, splenic and adrenal gene expressions were determined by real-time PCR. RESULTS: Overall, casp1(-/-) mice showed a lower inflammatory response than wt mice. The expression levels of powerful proinflammatory factors such as Nos2 and Ptgs2 was reduced in casp1(-/-) mice. Moreover, a hierarchical clustering analysis aimed at studying patterns of gene coexpression revealed large alterations in the hippocampal pattern of casp1(-/-) mice. Surprisingly, the expression of Adamts1 was increased in the hippocampus and adrenals of casp1(-/-) mice. CONCLUSIONS: The resilience of casp1(-/-) mice to SIRS lethality is associated with a lower inflammatory response, loss of hippocampal gene coexpression patterns, and increased hippocampal Adamts1 gene expression. The latter might be beneficial for casp1(-/-) mice, since ADAMTS1 is likely to play a role in neuronal plasticity. The mechanisms described here may help the development of either novel biomarkers or therapeutic targets against SIRS/sepsis.

Significance of Pathologic Response in Patients With Early and Locally Advanced Breast Cancer Treated With Neoadjuvant Chemotherapy in a Middle-Income Country. A Real-World Historical Cohort.

PURPOSE: Breast 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. METHODS: We 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. RESULTS: Three 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). CONCLUSION: A 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.

Use of contact force technology for cardiac arrhythmia ablation in children.

Background: New techniques for cardiac arrhythmia ablation, such as contact force (CF) technology, have emerged recently. These catheters provide information about adequate tissue contact for optimal lesions. In adults, these techniques have shown greater accuracy, reduced arrhythmia recurrence and complications, and higher success rates. However, data on pediatric patients are limited. Objective: The purpose of this study was to describe the experience with arrhythmia ablation using CF catheters in the pediatric population. Methods: A retrospective cross-sectional descriptive study of all patients <18 years old undergoing cardiac 3-dimensional mapping and ablation with CF between March 2016 and June 2022 was performed. Results: A total of 321 patients were included (51.40% male; mean age 12.26 years). The most frequent arrhythmia were supraventricular tachycardia (SVT) mediated by accessory pathways (APs) (atrioventricular reentrant tachycardia in 82.24%, ventricular arrhythmia in 11.21%, atrial tachycardia in 5.92%). Mean procedural time was 2.86 ± 1.2 hours, and average contact used was 14.33g ± 6.88g. The success rate of ablation was 97.82% with a low risk of complications. Conclusion: This is the largest published series of CF technology use in patients <18 years old. In the pediatric population, CF ablation is a safe procedure with high success rates and can be used for most arrhythmic substrates. The most frequent tachycardia observed in this study was SVT mediated by APs. Contact with 14g is safe and yields an excellent outcome in children. The presence of structural heart anomalies and previous ablation procedures decreased the success rate.

Diabetes Mellitus Type 1 has a Higher Impact on Corneal Endothelial Cell Density and Pachymetry than Diabetes Mellitus Type 2, Independent of Age: A Meta-Regression Model.

PURPOSE: Patients with diabetes mellitus (DM) often have keratopathy. However, the compromise of the corneal endothelium in type 1 DM (T1DM) and type 2 DM (T2DM) has so far not been well characterized. METHODS: We performed a systematic literature search to find articles on humans combining T1DM and/or T2DM and the corneal endothelium. The period was from inception to June 2020. The meta-regression evaluated the role of each type of DM on corneal endothelial cell density (CED) and pachymetry. The statistical models included age as a modulator to discriminate between the normal changes due to age and the effect of the disease and to determine the impact of the disease duration. RESULTS: The initial search identified 752 records, of which 17 were included in the meta-regression. Patients with T1DM had, on average, 193 cells/mm 2 lesser than control patients ( P < 0.00001). Patients with T2DM had 151 cells/mm 2 less compared with control patients ( P < 0.00001). The loss of corneal endothelial cells was expected because the aging was similar in patients with T1DM and T2DM and their control groups. Patients with T1DM and T2DM showed an increase in pachymetry versus control patients, and in both groups, it was associated with the duration of the disease. CONCLUSIONS: Both types of DM reduced CED and increased pachymetry. These differences were higher in patients with T1DM versus control patients than patients with T2DM versus control patients. In T1DM, CED reduction was not correlated with the time from diagnosis. In both groups, patients had CED reduction due to aging similar to that of their matched control patients.

Interaction Effect Between Hemoglobin and Hypoxemia on COVID-19 Mortality: an observational study from Bogotá, Colombia.

Purpose: We aimed to assess the effect of hemoglobin (Hb) concentration and oxygenation index on COVID-19 patients' mortality risk. Patients and Methods: We retrospectively reviewed sociodemographic and clinical characteristics, laboratory findings, and clinical outcomes from patients admitted to a tertiary care hospital in Bogotá, Colombia, from March to July 2020. We assessed exploratory associations between oxygenation index and Hb concentration at admission and clinical outcomes. We used a generalized additive model (GAM) to evaluate the observed nonlinear relations and the classification and regression trees (CART) algorithm to assess the interaction effects. Results: We included 550 patients, of which 52% were male. The median age was 57 years old, and the most frequent comorbidity was hypertension (29%). The median value of SpO2/FiO2 was 424, and the median Hb concentration was 15 g/dL. The mortality was 15.1% (83 patients). Age, sex, and SpO2/FiO2, were independently associated with mortality. We described a nonlinear relationship between Hb concentration and neutrophil-to-lymphocyte ratio with mortality and an interaction effect between SpO2/FiO2 and Hb concentration. Patients with a similar oxygenation index had different mortality likelihoods based upon their Hb at admission. CART showed that patients with SpO2/FiO2 < 324, who were less than 81 years with an NLR >9.9, and Hb > 15 g/dl had the highest mortality risk (91%). Additionally, patients with SpO2/FiO2 > 324 but Hb of < 12 g/dl and a history of hypertension had a higher mortality likelihood (59%). In contrast, patients with SpO2/FiO2 > 324 and Hb of > 12 g/dl had the lowest mortality risk (9%). Conclusion: We found that a decreased SpO2/FiO2 increased mortality risk. Extreme values of Hb, either low or high, showed an increase in the likelihood of mortality. However, Hb concentration modified the SpO2/FiO2 effect on mortality; the probability of death in patients with low SpO2/FiO2 increased as Hb increased.

Genomic characterization of SARS-CoV-2 and its association with clinical outcomes: a 1-year longitudinal study of the pandemic in Colombia.

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.

Clinical characteristics and mortality associated with COVID-19 at high altitude: a cohort of 5161 patients in Bogotá, Colombia.

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.

Gender and Polysomnographic Profiles Findings in Obstructive Sleep Apnea Syndrome Patients Living in High Altitude.

PURPOSE: Obstructive sleep apnea (OSA) is a common sleep disorder which prevalence is 22% in men and 17% in women. It is well described that females presented different clinical and polysomnographic characteristics compared with men. Those studies were performed in plain areas. We described the analysis by gender and clinical profiles of a sample of patients with diagnostic of OSA and living at high altitude. PATIENTS AND METHODS: It is an observational study that describes differences between clinical and polysomnographic characteristics by gender in patients with OSA. Additionally, an unsupervised cluster algorithm was used to find groups of patients with similar clinical and polysomnographic characteristics. RESULTS: We included 709 patients, 51.6% were females and 48.3% were males with mean age of 64 and 62 years old, respectively, in which 90.97% presented OSA. Men presented a higher apnea and hypopnea index than women (p=0.002), besides presented more sleep polysomnographic alterations. Meanwhile, women evidenced better sleep quality based on parameters. Additionally, in the sample of patients, we found four separated clinical profiles characterized mainly by differences in the severity of polysomnographic parameters. CONCLUSION: The patients were more obese, older, and had lower SpO2 values than most of those previously reported. Men had greater severity in most of the parameters measured by polysomnography. Polysomnographic variables were different both in the OSA patient profiles and in the gender comparison. However, the REM sleep apnea hypopnea index did not differ between sexes, indicating the importance of this variable in the evaluation of OSA severity in women. In contrast to previous reports, clinical and demographic characteristics showed few differences in both analyses. This result suggests that the behavior of OSA at high altitudes may have particularities with respect to low altitudes.

Impact of a pharmacist-based multidimensional intervention aimed at decreasing the risk of hyperkalemia in heart failure patients: A Latin-American experience.

AIMS: Hyperkalemia is a potentially life-threatening condition associated with the use of heart failure (HF) medications, which can lead to increased morbidity and mortality. Novel approaches for hyperkalemia prevention are needed, especially in limited-resource settings. Despite multiple studies showing the beneficial impact of pharmaceutical-counseling in several outcomes, there is a knowledge-gap regarding its impact on hyperkalemia prevention. METHODS: A case-control study was performed in patients from the Adult Heart Failure Clinic Registry in our institution. Cases were selected using a definition of serum potassium K+ ≥5.5 mmol/L. To study the association between hyperkalemia and relevant risk factors, we performed a multivariate logistic regression analysis using the Least Absolute Shrinkage and Selection Operator (LASSO) method for variable selection. We also fitted a Classification and Regression Tree (CART) to establish complex interactions and effect modifiers between the selected variables. RESULTS: We matched 483 controls (eligible HF patients without hyperkalemia) to 132 cases (eligible HF patients with hyperkalemia based on age and calendar, yielding a total sample size of 615 patients (270 females) for this study. Cases had statistically significant lower odds of receiving a pharmacist-based multidimensional intervention (PBMI) (OR 0.57; 95% CI, 0.43-0.80) or having HF with reduced ejection fraction (OR 0.56; 95% CI, 0.18-0.72). On the other hand, patients who presented hyperkalemia had statistically significant higher odds of having a history of chronic kidney disease stage 4 (OR 4.97; 95% CI, 2.24-11.01) or 5 (OR 6.73; 95% CI, 1.69-26.84) and being on enalapril at doses =40 mg/day (OR, 9.90; 95% CI 5.81-16.87). CONCLUSIONS: PBMI is a practical approach to prevent hyperkalemia in HF patients in a limited-resource setting. However, clinical trials are needed to assess its effectiveness.

Identifying the factors for improving quality of oral fluorescein angiography.

AIM: To evaluate the quality of oral fluorescein angiography (FA) in relation to food intake. METHODS: This is an observational, case-crossover study. We collected information from patients undergoing routine oral FA for retinal disease at the Shiley Eye Institute. Eighty patients (160 eyes) were analysed. Fasting and non-fasting images of the same patient were recorded, compared and analysed for different image quality parameters and clinical relevance by experienced retina specialists. RESULTS: When analysing the images, intergrader agreement was moderate to good with a Kappa averaging 0.60 (0.5-0.85). When patients were fasting pre-imaging, better angiography quality scores were achieved when compared with images taken when patients were non-fasting (mean 0.84 vs 0.72, p<0.001). Multivariate analysis showed that non-fasting patients with higher body mass index had the worst scores. Other clinical parameters, such as staining of drusen, staining of disciform scars or central and peripapillary atrophy, were also significantly better during the pre-fasting exam (p<0.001). Oral FA was approximately 22% faster (time to fluorescein dye appearance) under fasting conditions than non-fasting (mean±SD, minutes, 18.7±6.9 vs 25.14±8.1, p<0.001). CONCLUSION: Fasting oral FA provided significantly better quality images as well as faster optimal imaging times when compared with non-fasting oral FA. By improving its overall quality, oral FA could be a useful adjunctive examination to optical coherence tomography (OCT) and OCT angiography in patients who require FA studies but who have difficult access or refuse an invasive procedure.

Endothelial dysfunction and arterial stiffness in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Non-invasive surrogates of cardiovascular (CV) disease such as endothelial dysfunction (ED) and peripheral arterial stiffness (AS) have been evaluated in systemic lupus erythematosus (SLE) patients. The aim of this study was to systematically review and meta-analyze reports of cardiovascular disease (CVD) in SLE patients, as measured by ED and AS. METHODS: Studies analyzing the relationship of SLE with ED (flow-mediated dilatation [FMD], nitroglycerin-mediated dilatation [NMD] and peripheral arterial tonometry [PAT]) and AS (augmentation index [AIx], pulse wave velocity [PWV]) were systematically searched for in PubMed, Cochrane library, EMBASE, VHL, SciELO and Web of Science databases. Inclusion criteria included peer-review and English language. Mean differences (MD) and 95% confidence intervals (CIs) were estimated using the random effect model. The study was registered with PROSPERO, number CRD42019121068. RESULTS: The meta-analysis included 49 studies. FMD data from 18 studies including 943 SLE subjects (mean age = 38.71 [95%CI 36.21, 41.21] years) and 644 unaffected controls (mean age = 38.63 [95%CI 36.11, 41.15] years) were included. When compared with unaffected controls, FMD in SLE subjects was decreased by 4.3% (95%CI: -6.13%, -2.47%): p < 0.001). However, NMD did not significantly differ between SLE patients and controls (MD = - 2.68%; 95% CI -6.00, 0.62; p = 0.11). A significantly increased AS between SLE patients and controls according to overall PWV (MD = 1.12 m/s; 95% CI 0.72-1.52; p < 0.001) was observed, but not for the brachial-ankle PWV. AIx was also increased in SLE patients compared with healthy controls (MD = 4.55%; 95% CI 1.48-7.63; p = 0.003). CONCLUSIONS: Overall, SLE patients showed impaired FMD, an independent predictor of CV events. There was a higher degree of AS in SLE patients compared with controls. ED and AS in SLE should be considered when planning preventive strategies and therapies.