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.

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.

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.

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.

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.

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.

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.

High Prevalence of Abnormal Ocular Surface Tests in a Healthy Pediatric Population.

PURPOSE: To describe ocular surface characteristics and tests' results in a healthy pediatric population. METHODS: We performed a cross-sectional study with 60 healthy children, obtaining consent, OSDI and screen use survey and conducting ocular surface tests. Statistical univariate analysis for categorical and quantitative variables was made. To describe the correlation of the results in both eyes, we used a model of random effects. To characterize the possible profiles of device use, we applied the mixed-cluster methodology. RESULTS: Sixty healthy children between 7 and 17 years old were evaluated. Girl's proportion was 41.6%. Mean Ocular Surface Disease Index Score was 9.98±8.49 points. Daily screen time was 5.59±2.77 hours and the most popular screen was the smartphone. Mean results (with standard deviations or confidence intervals) of ocular surface tests were blink frequency while reading on paper, 6.8±5.68 times per minute; blink frequency while reading on screen, 8.7±7.14 times per minute; tear meniscus height, 0.19[0.18-0.2] mm; non-invasive tear break-up time, 12.44[10.99-13.9] seconds; nasal conjunctival redness, 0.86[0.77-0.94]; temporal conjunctival redness, 0.96[0.87-1.04]; tear osmolarity, 299.3[295.14-303.45] mmol; and Schirmer test, 23.73[21.28-26.18] mm. Lid margin was irregular in three eyes; 44.7% had thin lipid layer; lissamine green staining was positive in 70.8%; fluorescein staining was positive in 47.4%; 36.64% exhibited partial meibomian gland loss. CONCLUSION: Considering the scarcity of specific pediatric values of ocular surface tests, we performed a clinical investigation involving the complete pool of ocular surface tests in children. Although healthy children were included in this study, we found that all the participants had at least one abnormal result and 33.33% had dry eye disease diagnosis, according to the TFOS DEWS II. It would be relevant to carry out further multicentric studies to compare our ocular surface tests' results with other groups of children.

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.

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.

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.

Prevalencia de pacientes con queratocono en la Clínica Barraquer en Bogotá, Colombia / Prevalence of keratoconus patients at the Barraquer Clinic in Bogotá, Colombia

Introducción: Queratocono es un término clínico amplio, que describe un estado de la córnea derivado de su adelgazamiento focal y protrusión secundaria central, paracentral y/o periférica. Los reportes epidemiológicos globales revelan un amplio rango en cifras de prevalencia e incidencia que se podría explicar por las diferencias geográficas, factores de riesgo, tipo de población, métodos y criterios diagnósticos utilizados. En Colombia no hay estudios epidemiológicos que evalúen esta enfermedad de manera integral por lo que su frecuencia aún no ha podido ser determinada. Objetivo: identificar la prevalencia de Queratocono y Degeneración Marginal Pelucida (DMP) en el centro oftalmológico privado Clínica Barraquer, durante el periodo de tiempo comprendido entre enero de 2014 y enero de 2019. Diseño del estudio: estudio transversal de fuentes secundarias. Método: revisión de los registros médicos electrónicos de todos los pacientes que consultaron por primera vez; posteriormente, se filtraron por el diagnóstico de Ectasia Corneal y/o Queratocono. Cada una de las historias clínicas fue analizada por un oftalmólogo teniendo en cuenta los diagnósticos preestablecidos. Resultados: del grupo de 91.426 pacientes, 2.647 tenían Queratocono o DMP. Se estableció una prevalencia de Queratocono y DMP del 2.84%. La edad promedio al momento del diagnóstico fue de 29.7±12 años. El 42.8% eran mujeres y el 57.2% hombres. Conclusión: la ectasias corneales de tipo Queratocono y DMP, son enfermedades con una prevalencia significativa en la población colombiana evaluada en la clínica Barraquer; consideramos se requiere de programas de tamizaje visual para su detección y tratamiento oportunos.

Background: Keratoconus is a wide clinical term used to describe a corneal disease characterized by thinning and secondary central, paracentral or peripheral protrusion of the cornea. The global epidemiological reports reveal a wide range of prevalence and incidence, that may be explained by geographical differences, risk factors, kind of population, and methods and diagnostic criteria employed. There are no epidemiological studies to evaluate globally this disease in Colombia, therefore, its frequency has not been determined yet. Objective: to identify the prevalence of Keratoconus and Pellucid Marginal Degeneration (PMD) from January 2014 to January 2019 at the private ophthalmological center Clínica Barraquer. Study Design: cross-sectional study using secondary data. Method: a review of the electronic medical records of all patients who consulted for the first time was performed, and then, filtered by the initial diagnosis of Corneal Ectasia or Keratoconus. Each one of the medical records was analyzed by an ophthalmologist taking into account a series of pre-established diagnostic criteria. Results: of 91.426 patients, 2.647 had Keratoconus or PMD within the time interval of the study. A prevalence of 2.84% was determined in first time patients. The average age at the time of diagnosis was 29.7±12 years. 42.8% were female patients and 57.2% male patients. Conclusion: Keratoconus and PMD are diseases with significant prevalence in the Colombian population evaluated at the Barraquer clinic, thus, visual screening programs are required for accurate detection and treatment.

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.

Juvenile polyautoimmunity in a rheumatology setting.

Overt polyautoimmunity (PolyA) corresponds to the presence of more than one well-defined autoimmune disease (AD) manifested clinically in a single patient. The current study aimed to describe the main characteristics of juvenile PolyA in a pediatric rheumatology setting and analyze the chronological aspects, index cases, familial autoimmunity, and clustering pattern. This was a cross-sectional and multicenter study in which 313 children with overt PolyA were included. Patients were systematically interviewed and their medical records reviewed using a questionnaire that sought information about demographic, clinical, immunological, and familial characteristics. A hierarchical cluster analysis was done to determine similarities between autoimmune diseases based on PolyA. PolyA occurred simultaneously in 138 (44%) patients. Multiple autoimmune syndrome was observed in 62 (19.8%) patients. There were 25 index diseases of which, systemic lupus erythematosus (SLE, n = 134, 42.8%), juvenile idiopathic arthritis (JIA, n = 40, 12.7%), Hashimoto's thyroiditis (HT, n = 24, 7.66%), immune thrombocytopenic purpura (ITP n = 20, 6.39%), antiphospholipid syndrome (APS, n = 15, 4.79%), and vitiligo (VIT, n = 15, 4.79%) were the most frequent and represented 79.23% of the total number of patients. Familial autoimmunity influenced PolyA. A high aggregation of autoimmunity was observed (λr = 3.5). Three main clusters were identified, of which SLE and APS were the most similar pair of diseases (based on the Jaccard index) followed by HT and JIA, which were related to ITP and Sjögren's syndrome. The third cluster was composed of localized scleroderma and VIT. Our findings may assist physicians to make an early diagnosis of this frequent condition. Pediatric patients with ADs should be systematically assessed for PolyA.

Geoepidemiology of Sjögren's syndrome in Latin America.

OBJECTIVE: To evaluate the geoepidemiology of Sjögren's syndrome (SS) in Latin America. METHODS: This was a three phase study in which original data from a Colombian cohort of patients with SS is presented, followed by a systematic review of Colombian and Latin American studies. Lastly, the geoepidemiology of SS in Latin America was assessed by comparing the clinical characteristics of the region with those of the rest of the world by means of a meta-analysis approach. RESULTS: Data from 2970 patients from Latin America and 18019 patients from Europe, North America and Asia were analyzed. Colombian patients have a lower age at disease onset than those from other Latin American countries and a higher rate of positivity of antinuclear antibodies and rheumatoid factor. A significant difference in the proportion of female patients in Latin America compared with Europe and North America was observed. The spectrum of disease in Latin American was similar to North American patients, while strong differences were noticed between Latin American and European and Asian patients. Noteworthy, a paucity of reports including African and African-descendent patients was observed. CONCLUSIONS: The clinical spectrum of SS differs between countries and continents. Genetic differences relying upon ancestry could explain these findings. However, environmental factors have proven to be important determinants in the development of autoimmune diseases (i.e., autoimmune ecology). Thus, ancestry and the autoimmune ecology should be considered in studies aimed to evaluate the geoepidemiology of SS and other autoimmune diseases.

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.