Youth Firearm Mortality in the Americas From 2015 to 2022.

This cross-sectional study uses national vital statistics on firearm mortality to investigate trends in firearm deaths among youths in the US, Brazil, Mexico, and Colombia.

Phase Ib Study for the Combination of Doxorubicin, Dacarbazine, and Nivolumab as the Upfront Treatment in Patients With Advanced Leiomyosarcoma: A Study by the Spanish Sarcoma Group (GEIS).

PURPOSE: Doxorubicin, alongside a select group of cytotoxic agents, is capable of inducing an adaptive immune response via a well-established peculiar type of tumor cell death called immunogenic cell death (ICD). We hypothesize that combining doxorubicin and dacarbazine with nivolumab may enhance therapeutic efficacy by exerting synergy in the ICD circuit. We hereby present a phase Ib trial with this combination. PATIENTS AND METHODS: Patients with advanced leiomyosarcoma and anthracycline-naïve were eligible. The initial dose level consisted of doxorubicin 75 mg/m2 once on day 1, once every three weeks, followed by dacarbazine 400 mg/m2 once on days 1 and 2, once every three weeks, plus nivolumab 360 mg once on day 2, once every 3 weeks, for six courses and then 1 year of nivolumab. A (-1) dose level was the same regimen but with nivolumab 240 mg. A classic 3 + 3 phase-I design was used to determine the recommended phase-II dose (RP2D). Secondary end points included overall response rate, safety profile, survival, and translational research. RESULTS: From January 2002 to July 2023, 24 patients were enrolled and 23 were evaluable for efficacy, excluding one patient because of noncompliant dose. All patients were treated with the initial dose level, then the RP2D. Toxicity was mild, with the most frequent being grade 4 toxicity neutropenia (16.7%) and thrombocytopenia (8.3%), while no grade 5 toxicity occurred. The centrally reviewed objective response rate was as follows: partial response 56.5%, stable disease 39.1%, and progression 4.4%. The 6-month progression-free survival (PFS) rate was 80% (95% CI, 63 to 98). Dynamic increases of HMGB1 in blood significantly correlated with longer PFS. CONCLUSION: This scheme of doxorubicin, dacarbazine, and nivolumab is feasible and well tolerated. Clinical activity is encouraging and the prognostic impact of HMGB1 supports the relevance of ICD activation. Further clinical research is already underway with this concept in leiomyosarcoma.

Impact of Age on Perioperative Complications After Obliterative Vaginal Surgery.

IMPORTANCE: Obliterative vaginal surgery is often reserved for older patients with prolapse, but the effect of age as an independent risk factor for perioperative complications in this cohort is poorly understood. OBJECTIVE: The aim of this study was to assess the association between age and perioperative complications in women undergoing obliterative vaginal surgery. STUDY DESIGN: This was a retrospective cohort study that included 371 patients undergoing colpocleisis between 2010 and 2013 at a single academic medical center. Seventy demographic and clinical variables, including complications within 12 weeks of surgery, were analyzed. The χ2 and Fisher exact tests were used for categorical variables. Student t and Mann-Whitney U tests were used for continuous variables. Univariate logistic regression was performed to identify predictors of perioperative complications, and candidate variables with P < 0.2 were used in multivariate logistic regression. RESULTS: The mean patient age was 75.4 ± 6.4 years (range, 59-94 years). One hundred ten (29.7%) patients experienced at least 1 complication, the most common of which was urinary tract infection (n = 47, 12.7%). In the final multivariable model, only age (odds ratio, 1.05 per year; 95% confidence interval, 1.01-1.08) remained a significant predictor of perioperative complications. A cut point of age ≥70.5 years maximized sensitivity and specificity for predicting complications. CONCLUSIONS: Among women undergoing obliterative vaginal surgery, age is a predictor of perioperative complications. Each increasing year of age increases the complication likelihood by 1.05-fold, such that an 85-year-old woman is 1.05^20 or 2.65 times more likely than a 65-year-old woman to have a complication. A cut point of ≥70.5 years best predicted complications. Despite this association, severe perioperative complications following obliterative surgery are rare.

A Qualitative Exploration of Women With Cystic Fibrosis and Urinary Incontinence.

IMPORTANCE: Women with cystic fibrosis (CF) historically experience a high prevalence of urinary incontinence (UI). However, this area is understudied, especially in the modern era of highly effective modulator therapy (HEMT). OBJECTIVE: This study aimed to explore the UI experiences, knowledge, care-seeking behavior, and treatment preferences of women with CF. STUDY DESIGN: We recruited women aged ≥18 years through the CF Foundation's Community Voice national registry if they had a diagnosis of CF and reported UI. Participants underwent individual, semistructured interviews exploring their experiences, attitudes, and preferences toward UI that were audiorecorded and transcribed. Two coders performed thematic analysis using deductive and inductive coding approaches. RESULTS: Twenty-six participants completed interviews (average age, 45.1 years; range, 24-61 years). Key themes included the following: (1) most women with CF and UI report low bother from symptoms likely related to stress UI, and HEMT has greatly improved UI symptoms and decreased bother; (2) most women with CF and UI had previously discussed UI symptoms with family and/or peers but had not sought care due to stigma or low priority; (3) women with CF and UI had minimal knowledge about UI in general and how it relates to CF; (4) most desired broad screening for UI from their CF team and improved multidisciplinary care; and (5) highly effective UI treatment options with low-time commitment and easily accessible resources are desired. CONCLUSIONS: Women with CF and UI report low knowledge and care-seeking behavior related to this condition and desire improved care provision. Importantly, HEMT may improve UI symptoms among people with CF.

Characterization of HER2-Low Breast Tumors among a Cohort of Colombian Women.

HER2-low tumors have shown promise in response to antibody-drug conjugates (ADCs) in recent clinical trials, underscoring the need to characterize this group's clinical phenotype. In this study, we aimed to explore the clinicopathological features, survival rates, and HER2 amplicon mRNA expression of women affected with HER2-low breast cancer, compared with HER2-negative and HER2-positive groups. We included 516 breast cancer patients from Colombia, for whom we compared clinicopathological features, mRNA expression of three HER2 amplicon genes (ERBB2, GRB7 and MIEN1), survival and risk of mortality between HER2-low cases (1+ or 2+ with negative in situ hybridization (ISH) result) with HER2-positive (3+ or 2+ with positive ISH test) and HER2-negative (0+) cases. A higher proportion of patients with better-differentiated tumors and a lower proliferation index were observed for HER2-low tumors compared to the HER2-positive group. Additionally, HER2-low tumors showed higher mRNA expression of the ERBB2 gene and longer overall survival rates compared to HER2-negative cases. Nonetheless, a Cox-adjusted model by ER status and clinical stage showed no statistically significant differences between these groups. Our results show differences in important clinicopathological features between HER2-low and both HER2-positive and negative tumors. Given this unique phenotype, it is crucial to evaluate the potential advantages of ADC therapies for this emerging subtype of breast cancer.

Extortion experiences of recent adult immigrants from Latin America: self-reported prevalence, associated costs, and current mental health.

Violence across Latin America is an increasingly important factor influencing migration to the US. A particular form of violence that is experienced by many Latinx migrants is extortion. This research analyzes the extortion experiences of Latinx immigrant adults arriving at the US southern border and the impact these experiences have on mental health. We find that on average, participants paid $804 in extortion during their migration. The most common perpetrators of extortion in our study were police followed by immigration officials throughout Latin America. Pregnant participants were less likely to experience extortion and adults traveling with children were more likely to be extorted. Participants who were extorted for money reported significantly greater severity of post-traumatic stress disorder (PTSD) symptoms compared to those who were not extorted. This research is the first of its kind to analyze extortion experiences among Latinx immigrants to the US, quantifying the prevalence, amounts paid, countries where extortion occurs, and perpetrators of extortion. In addition, extortion experiences are associated with negative effects on the mental health of newly arrived Latinx immigrants to the US. Based upon these findings, we recommend that extortion should be considered a significant stressor in the migrant experience, particularly for those adults traveling with children.

Improving well-being among women in neonatology.

OBJECTIVE: To evaluate the factors that improve professional and personal well-being amongst women in neonatology (WiN). STUDY DESIGN: A 30-question survey of multiple choice, rank order, and open-ended questions focused on professional and personal factors that affect the well-being of WiN members. Quantitative and qualitative methods were used to determine leading factors and themes. RESULTS: Of 326 respondents, 64% felt "well" professionally over half of the time. Professional well-being was most affected by scheduling flexibility, helping patients, administrative and staffing support, feelings of being valued, and clinical workload/acuity. Time for family and self-care, having domestic help, and scheduling flexibility were factors that most positively impacted personal well-being. CONCLUSION: In this national survey, WiN members identified the factors that can improve their well-being. Strategic planning and targeted interventions are urgently needed to enhance work-life integration and job satisfaction, leading to improved neonatal workforce retention and improved quality of patient care.

Examining firearm-related deaths in Mexico, 2015-2022.

BACKGROUND: Globally, Mexico is one of six countries with the highest level of firearm mortality. While previous studies have examined firearm mortality in Mexico before 2015, increases in violence since then highlight the need for an updated analysis. In this study, we examined changes in firearm-related deaths in Mexico from 2015 to 2022 and described these deaths by key demographic groups, incident location, and state of occurrence. Data came from Mexico's Instituto Nacional de Estadistica y Geografia (INEGI), a federal agency that collects and reports national population data. We used descriptive statistics to analyze rates, proportions, and percentage changes in firearm mortality, and we displayed temporal trends using time plots and special trends using maps. RESULTS: Firearm deaths increased in Mexico from 2015 to 2018 but slightly decreased from 2018 to 2022. Homicides presented the highest increase and the highest proportion of firearm-related deaths from 2015 to 2022. Victims were primarily males but rates among women increased at a higher proportion (99.5% vs 53.5%). One third of victims were 20-29y but rates among children and adolescents (10-9y) increased at a higher proportion. Most firearm-related deaths occurred in streets or public spaces but the percentage of incidents occurring in households have increased. State-level rates and percentage changes varied significantly. States with higher rates of firearm mortality coincide with those involving conflict among organized criminal organizations. CONCLUSION: Firearm mortality in Mexico is a major public health burden. The epidemiology of firearm-related deaths in Mexico varies by intent, demographics, location, and states. To mitigate this challenge, multiple solutions are required.

Genetic ancestry is related to potential sources of breast cancer health disparities among Colombian women.

Breast cancer health disparities are linked to clinical-pathological determinants, socioeconomic inequities, and biological factors such as genetic ancestry. These factors collectively interact in complex ways, influencing disease behavior, especially among highly admixed populations like Colombians. In this study, we assessed contributing factors to breast cancer health disparities according to genetic ancestry in Colombian patients from a national cancer reference center. We collected non-tumoral paraffin embedded (FFPE) blocks from 361 women diagnosed with breast cancer at the National Cancer Institute (NCI) to estimate genetic ancestry using a 106-ancestry informative marker (AIM) panel. Differences in European, Indigenous American (IA) and African ancestry fractions were analyzed according to potential sources of breast cancer health disparities, like etiology, tumor-biology, treatment administration, and socioeconomic-related factors using a Kruskal-Wallis test. Our analysis revealed a significantly higher IA ancestry among overweight patients with larger tumors and those covered by a subsidized health insurance. Conversely, we found a significantly higher European ancestry among patients with smaller tumors, residing in middle-income households, and affiliated to the contributory health regime, whereas a higher median of African ancestry was observed among patients with either a clinical, pathological, or stable response to neoadjuvant treatment. Altogether, our results suggest that the genetic legacy among Colombian patients, measured as genetic ancestry fractions, may be reflected in many of the clinical-pathological variables and socioeconomic factors that end up contributing to health disparities for this disease.

Traumatic experiences and place of occurrence: An analysis of sex differences among a sample of recently arrived immigrant adults from Latin America.

With increasing violence, political, and economic instability in Latin America, there is a record number of migrants crossing the U.S. southern border. Latin American migrants are often exposed to traumatic events before leaving their home country and during migration. While prior studies document that sex may play a role in types of traumatic exposure, few studies compare differences in traumatic exposure by sex and place of occurrence of recently arrived immigrants. Addressing this gap, we recruited 120 adults who had recently crossed the U.S.-Mexico border. Participants completed questionnaires to characterize trauma exposures in their home country and during their migration journey. Results found that men reported higher levels of exposure to combat situations, while women were more likely to experience sexual assault. Both combat exposure and sexual traumas occurred more often in home countries than during migration. More than half of the full sample reported being threatened with a firearm. These data confirm gender differences in type of trauma and that exposures in the country of origin may provide the impetus to migrate.

Feasibility and reliability of a quality indicator system for an ambulatory dispensing service.

Background: For a medication dispensing service to function with quality, continuous evaluation is required, which is why it is necessary to have reliable measurement tools that make it possible. Quality indicators can serve as tools for managing quality, as they are variables that directly or indirectly measure changes in a situation and help evaluate the progress made in addressing it. This article aims to determine the feasibility and reliability of a quality indicator system for a drug dispensing service for paediatric outpatients in two Mexican hospitals. Methods: A study of the development type of health systems and services at a microlevel was conducted from October 2020 to October 2021 in the pharmaceutical service of two Mexican hospitals. To determine the feasibility of the quality indicators, a retrospective evaluation was performed, which considered the indicators that could be calculated with the available information to be feasible. To determine reliability, an inter-observer agreement study (Kappa (κ)) was performed. Results: The feasibility analysis revealed that all five reference indicators related to the structure were feasible in both hospitals. In the Infantil of the Californias hospital, all six process indicators evaluated were feasible, whilst only one was found feasible in H+ Querétaro. As for outcome indicators, only one was feasible in the Infantil of the Californias hospital. The causes of non-feasibility in both hospitals were the non-documentation of the primary data related to the stages of the process and the lack of instruments to measure patient satisfaction. The reliability of the indicators showed little variability. Conclusion: Although not all indicators were feasible, solutions were proposed so that the 15 reference indicators could be used if an organization decided to do so. The reliability of the indicators was demonstrated, evidencing the importance of the data sheet as a tool to generate valid reliable measures.This article is part of the Hospital pharmacy, rational use of medicines and patient safety in Latin America Special Issue: https://www.drugsincontext.com/special_issues/hospital-pharmacy-rational-use-of-medicines-and-patient-safety-in-latin-america/.

Treatment patterns and persistence on disease modifying therapies for multiple sclerosis and its associated factors.

BACKGROUND: Effective interventions for Multiple Sclerosis require timely treatment optimization which usually involves switching disease modifying therapies. The patterns of prescription and the reasons for changing treatment in people with MS, especially in low prevalence populations, are unknown. OBJECTIVES: To describe the persistence, reasons of DMT switches and prescription patterns in a cohort of Colombian people with MS. METHODS: We conducted a retrospective observational study including patients with confirmed MS with at least one visit at our centre. We estimated the overall incidence rate of medication changes and assessed the persistence on medication with Kaplan-Meier survival estimates for individual medications and according to efficacy and mode of administration. The factors associated with changing medications were assessed using adjusted Cox proportional-hazards models. The reasons for switching medication changes were described, and the prescription patterns were assessed using network analysis, with measures of centrality. RESULTS: Seven hundred one patients with MS were included. Mean age was 44.3 years, and 67.9% were female. Mean disease duration was 11.3 years and 84.5% had relapsing MS at onset, with median EDSS of 1.0. Treatment was started in 659 (94%) of the patients after a mean of 3 years after MS symptom onset. Among them, 39.5% maintained their initial DMT, 29.9% experienced a single DMT change, while 18.7% went through two, and 11.9% had three or more DMT changes until the final follow-up. The total number of treatment modifications reached 720, resulting in an incidence rate of 1.09 (95% confidence interval: 1.01-1.17) per patient per year The median time to change after the first DMT was 3.75 years, and was not different according to the mode of administration or efficacy classification. The main reasons for changing DMT were MS activity (relapses, 56.7%; MRI activity, 18.6%), followed by non-serious adverse events (15.3%) and disability (11.1%). Younger age at MS onset, care under our centre and insurer status were the main determinants of treatment change. Network analysis showed that interferons and fingolimod were the most influential DMTs. CONCLUSIONS: A majority of patients switch medications, mostly due to disease activity, and in association with age and insurer status.

Increased Incidence of TdT-negative Pre-B Acute Lymphoblastic Leukemia Associated With Poor Prognostic Features Among Mexican Children in Central Mexico.

Mexican and Hispanic children in Mexico and the United States, respectively, have the highest incidence and worst outcomes of pre-B acute lymphoblastic leukemia (ALL) compared with other racial/ethnic groups. Terminal deoxynucleotidyl transferase (TdT) is an intranuclear DNA polymerase normally present on immature lymphocytes (TdT-positive) and distinguishes ALL from mature lymphoid malignancies. We performed a multisite retrospective study to determine the incidence of TdT-negative precursor B-cell acute lymphoblastic leukemia (pre-B ALL) among Mexican, Caucasian, and US-born Hispanic children to correlate TdT expression with patient characteristics and known prognostic factors. Fisher exact test was performed for categorical variables and the Wilcoxon rank-sum test was used for continuous variables. TdT-negative pre-B ALL was most frequently identified in patients with National Cancer Institute high-risk disease ( P =0.014). TdT-negative expression was also most frequently associated with hypodiploid pre-B ALL ( P =0.001) and KMT2A gene rearrangement ( P =0.0012). Mexican children had the highest incidence of TdT-negative ALL compared with Caucasians and US Hispanics ( P <0.001), with an increased incidence of poor prognostic features as well. This study demonstrates significant differences in TdT-negative expression, genomic alterations, and leukemic ploidy based on race and ethnicity.

Seasonality and clinical characteristics of MS in an equatorial country.

BACKGROUND: Month and season of birth have been associated with risk of multiple sclerosis (MS), but there is relatively little evidence regarding their influence on the timing and severity of disease at onset. OBJECTIVE: To assess whether month and season of birth influence the age and phenotype at onset of MS as well as its severity in a cohort of Colombian patients. METHODS: This study is an analysis on MS cases only, drawn from a previously published case-control study. MS cases confirmed with current diagnostic criteria cared for at least once in our center were included. We assessed the influence of the month and season of birth in the age at MS onset, MS severity score, and age-related MS severity score using multiple and pairwise comparisons. Age at onset was also studied using Kaplan-Meier survival estimates compared with the log-rank test. The likelihood of progressive MS onset was evaluated with OR estimated from logistic regression models adjusted for age at onset and sex. RESULTS: 668 MS cases were included. No significant differences were found in the age at MS onset according to month of birth or season of birth. Neither month of birth nor season of birth conferred significant differences in MS severity score or age-related MS severity score. No significant association was found between month (ORs ranging from 0.62 to 3.11, none significant) or season of birth (OR 0.91; 95 %CI: 0.46-1.84) with primary progressive MS. CONCLUSION: The month or season of birth do not appear to influence the age onset and phenotype of MS in our country.

Tumor infiltrating lymphocytes (TILs) are a prognosis biomarker in Colombian patients with triple negative breast cancer.

Triple negative breast cancer (TNBC) is highly immunogenic and high levels of tumor infiltrating lymphocytes (TILs) have been associated with a better prognosis and higher probability to achieve pathological complete response. Here, we explore the potential role of stromal TILs level and composition as a prognostic and predictive biomarker in TNBC. 195 Tumor biospecimens from patients diagnosed with TNBC were included. Stromal TILs (sTILs), positive CD4/CD8 cells were evaluated. Differences in clinic-pathological characteristics according to immune infiltration were assessed. The predictive and prognostic value of immune infiltration was analyzed by multivariate models. Higher immune infiltration was observed in patients with favorable clinical-pathological features. Survival analysis showed that longer overall survival times were observed in patients with a higher infiltration of sTILs (p = 0.00043), CD4 + (p = 0.0074) and CD8 + (p = 0.008). In the multivariate analysis, low levels of sTILs were found to be associated with a higher mortality hazard (HR: 1.59, 95% CI 1.01-2.48). CD4 and CD8 immune infiltration were associated with higher odds for pathological complete response (OR: 1.20, 95% CI 1.00-1.46, OR: 1.28, 1.02-1.65, respectively). Our results suggest that immune infiltration could be used as a prognostic marker for overall survival in TNBC patients.

Enfermedad asociada a anticuerpos contra la glicoproteína de mielina de oligodendrocitos / Myelin oligodendrocyte glycoprotein antibody disease

Introducción: La enfermedad asociada a anticuerpos contra la glicoproteína de mielina del oligodendrocito (MOGAD, por sus siglas en inglés) es una entidad clínica recientemente identificada. La frecuencia de presentación del MOGAD es desconocida, pero se considera baja con respecto a otras enfermedades inflamatorias desmielinizantes. Materiales y métodos: Revisión narrativa de la literatura. Resultados: Las manifestaciones clínicas de esta condición son heterogéneas e incluyen neuritis óptica, mielitis, desmielinización multifocal del sistema nervioso central y encefalitis cortical. Se han descrito algunos hallazgos radiológicos que aumentan la sospecha diagnóstica, como el realce perineural del nervio óptico, el signo de la H en el cordón espinal y la resolución de lesiones T2 con el tiempo. El diagnóstico se basa en la detección de inmunoglobulinas G específicas contra MOG, en el contexto clínico adecuado. El tratamiento consiste en manejo de los ataques agudos con dosis altas de corticoides y en algunos casos se deberá considerar la inmunosupresión crónica, considerar la inmunosupresión crónica en pacientes con recurrencia o con discapacidad severa residual tras el primer evento. Conclusiones: En esta revisión narrativa se resumen los aspectos clave con respecto a la fisiopatología, las manifestaciones, el diagnóstico y el tratamiento de la MOGAD.

Introduction: The disease associated with antibodies against the myelin oligodendrocyte glycoprotein (MOGAD) is a recently identified clinical entity, with unknown frequency, but is considered low compared to other demyelinating inflammatory diseases. Materials And Methods: Narrative review. Results: The clinical manifestations are heterogeneous, ranging from optic neuritis or myelitis to multi-focal CNS demyelination or cortical encephalitis. There have been described characteristic MRI features that increase the diagnostic suspicion, such as perineural optic nerve enhancement, spinal cord H-sign or T2-lesion resolution over time. The diagnosis is based on the detection of specific G- immunoglobulins against MOG, in the suggestive clinical context. Acute treatment is based on high dose steroids and maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the first attack. Conclusions: In this narrative review, fundamental aspects of pathophysiology, clinical and radiological manifestations, diagnosis and treatment of MOGAD are discussed.

A comparison of PTSD and traumatic event rates in a clinical sample of non-refugee immigrants and native-born individuals with a psychotic disorder: a case-control study.

Background: Migration is a multi-stage social process linked to traumatic event exposure and a notably increased risk of psychosis. Although these conditions affect refugee and non-refugee immigrants, prior trauma research has focused mainly on the refugee population.Objective: To compare and describe the rate and the clinical characterization of PTSD and traumatic events between non-refugee immigrants and native-born individuals with psychotic disorder.Methods: 99 immigrants and 99 native-born individuals (n = 198) with at least one psychotic episode according to DSM-5 criteria were compared on the rate of PTSD diagnosis and traumatic events, using standardized and validated trauma scales.Results: In the non-refugee immigrant group, 31% met diagnostic criteria for PTSD compared to only 7.1% in the native-born group. Total scores in childhood trauma and last year stressful events were 1.5 and 2 times higher in non-refugee immigrants, respectively. Likewise, cumulative lifetime trauma was three times higher in non-refugee immigrants. Finally, non-refugee immigrants reported more violent and life-threatening traumatic events than native-born individuals.Conclusions: These results are relevant since they highlight that non-refugee immigrants with psychotic disorders are highly trauma-exposed, meaning a routine trauma assessment and a trauma-focused intervention for this population should be included in individualized treatment plans.

Traumatic events and PTSD rates in the non-refugee immigrant population with psychotic disorder have previously received scant attention.This study found that in a psychotic population, 31% of the non-refugee immigrants presented a PTSD diagnosis compared to only 7.1% of the native-born individuals.Compared to native-born individuals with psychosis, non-refugee immigrants with psychosis have 1.5 times more childhood trauma exposure, 2 times more stressful events in the past year and 3 times more cumulative trauma over their lifetime.

Multiple sclerosis functional tests and their comparability with self-administered values: A pilot study / Pruebas funcionales en esclerosis múltiple y su comparabilidad con los valores de administración autónoma: estudio piloto.

Introduction: Neurological impairment in multiple sclerosis is highly variable among patients and over time it is difficult to quantify. The Multiple Sclerosis Outcome Assessment Consortium established sensitive, cost-effective, clinically significant, and reproducible measures of different functional systems to measure outcomes in clinical trials. However, their use in clinical care routines is not widespread due to time and training constraints. Objective: To evaluate the self-administration feasibility of the timed 25-foot walking, symbol-digit-modality, and 9-peg hole tests in healthy individuals. Materials and methods: We performed a descriptive pilot study. Healthy individuals between 18 and 80 years of age were included. The Timed 25-Foot Walking Test (T25- FWT), the Symbol Digit Modality Test (SDMT), and the Nine-Hole Peg Test (9-HPT) (using the dominant and non-dominant hand) were administered by a trained physician, who also instructed the subjects about test self-administration. The correlation and agreement, between the guided and self-administered tests were assessed with Pearson and Spearman coefficients and the Bland-Altman method. Results: Thirty-eight healthy volunteers were included. The median age was 36 (range: 23-55) years old, and 55.26% were female. The correlation coefficient between guided and selfadministered tests was 0.37 for the T25-FWT (p=0.01), 0.54 for the SDMT (p<0.001), and 0.64 and 0.65 for the 9-HPT, in the dominant and non-dominant hands, respectively (p<0,001). Both forms of administration were concordant for the T25-FWT (95%CI: -1,49 to 1,43), the 9-HPT with dominant hand (95%CI: -5,23 to 4,09), the 9-HPT with non-dominant hand (95%CI: -7,75 to 7,14) and the SDMT (95% CI: -20,94 to 24,10). Conclusions: We provide a proof of concept related to the feasibility of the selfadministration of the T25-FWT, the 9-HPT, and the SDMT, as a tool to improve monitoring in routine clinical practice.

Introducción: El deterioro neurológico en la esclerosis múltiple es variable para cada paciente y su cuantificación se dificulta con el tiempo. El Multiple Sclerosis Outcome Assessment Consortium estableció medidas clínicas sensibles, costo-efectivas y reproducibles para medir los resultados de los estudios clínicos. Sin embargo, sus valores de referencia se desconocen y, en la atención habitual, su uso no está extendido por limitaciones de tiempo y entrenamiento. Objetivo: Establecer la factibilidad de la administración autónoma de las pruebas de marcha de 25 pies, símbolos y dígitos, y clavijas y nueve hoyos en individuos sanos. Materiales y métodos: Se realizó un estudio piloto descriptivo. Se incluyeron individuos sanos entre los 18 y los 80 años. Las pruebas de Timed 25-Foot Walking Test (T25-FWT) [caminata cronometrada de 25 pies], Symbol Digit Modality Test (SDMT) [símbolos y dígitos] y Nine-Hole Peg Test (9-HPT) [clavijas y nueve agujeros] fueron administradas por un médico capacitado, quien también instruyó a los sujetos sobre la administración autónoma de las pruebas. La correlación y la concordancia entre la prueba guiada y la autónoma se evaluaron con los coeficientes de Pearson y Spearman, y el análisis gráfico de Bland-Altman. Resultados: Se incluyeron 38 voluntarios sanos. La mediana de edad fue de 36 (rango: 23-55 años) y el 55,26 % eran mujeres. El coeficiente de correlación entre la prueba de administración guiada y la autónoma fue de 0,37 para la T25-FWT (p=0,01), de 0,54 para la SDMT (p<0,001) y de 0,64 y 0,65 para la 9-HPT, en las manos dominante y no dominante, respectivamente (p<0,001). Ambas formas de administración fueron concordantes para las pruebas T25-FWT (IC95%: -1,49 a 1,43), 9-HPT con la mano dominante (IC95%: -5,23 a 4,09), 9-HPT con la mano no dominante (IC95%: -7,75 a 7,14) y SDMT (IC95%: -20,94 a 24,10). Conclusiones: Los resultados de este estudio ayudan a determinar los valores de normalidad poblacional obtenidos con las pruebas T25-FWT, 9-HPT y SDMT; además, establecen la posibilidad de practicarlas de forma autónoma.

Pruebas funcionales en esclerosis múltiple y su comparabilidad con los valores de administración autónoma: estudio piloto / Multiple sclerosis functional tests and their comparability with self-administered values: A pilot study

Introducción. El deterioro neurológico en la esclerosis múltiple es variable para cada paciente y su cuantificación se dificulta con el tiempo. El Multiple Sclerosis Outcome Assessment Consortium estableció medidas clínicas sensibles, costo-efectivas y reproducibles para medir los resultados de los estudios clínicos. Sin embargo, sus valores de referencia se desconocen y, en la atención habitual, su uso no está extendido por limitaciones de tiempo y entrenamiento. Objetivo. Establecer la factibilidad de la administración autónoma de las pruebas de marcha de 25 pies, símbolos y dígitos, y clavijas y nueve hoyos en individuos sanos. Materiales y métodos. Se realizó un estudio piloto descriptivo. Se incluyeron individuos sanos entre los 18 y los 80 años. Las pruebas de Timed 25-Foot Walking Test (T25-FWT) [caminata cronometrada de 25 pies], Symbol Digit Modality Test (SDMT) [símbolos y dígitos] y Nine-Hole Peg Test (9-HPT) [clavijas y nueve agujeros] fueron administradas por un médico capacitado, quien también instruyó a los sujetos sobre la administración autónoma de las pruebas. La correlación y la concordancia entre la prueba guiada y la autónoma se evaluaron con los coeficientes de Pearson y Spearman, y el análisis gráfico de Bland-Altman. Resultados. Se incluyeron 38 voluntarios sanos. La mediana de edad fue de 36 (rango: 23-55 años) y el 55,26 % eran mujeres. El coeficiente de correlación entre la prueba de administración guiada y la autónoma fue de 0,37 para la T25-FWT (p=0,01), de 0,54 para la SDMT (p<0,001) y de 0,64 y 0,65 para la 9-HPT, en las manos dominante y no dominante, respectivamente (p<0,001). Ambas formas de administración fueron concordantes para las pruebas T25-FWT (IC95%: -1,49 a 1,43), 9-HPT con la mano dominante (IC95%: -5,23 a 4,09), 9-HPT con la mano no dominante (IC95%: -7,75 a 7,14) y SDMT (IC95%: -20,94 a 24,10). Conclusiones. Los resultados de este estudio ayudan a determinar los valores de normalidad poblacional obtenidos con las pruebas T25-FWT, 9-HPT y SDMT; además, establecen la posibilidad de practicarlas de forma autónoma.

Introduction. Neurological impairment in multiple sclerosis is highly variable among patients and over time it is difficult to quantify. The Multiple Sclerosis Outcome Assessment Consortium established sensitive, cost-effective, clinically significant, and reproducible measures of different functional systems to measure outcomes in clinical trials. However, their use in clinical care routines is not widespread due to time and training constraints. Objective. To evaluate the self-administration feasibility of the timed 25-foot walking, symbol-digit-modality, and 9-peg hole tests in healthy individuals. Materials and methods. We performed a descriptive pilot study. Healthy individuals between 18 and 80 years of age were included. The Timed 25-Foot Walking Test (T25- FWT), the Symbol Digit Modality Test (SDMT), and the Nine-Hole Peg Test (9-HPT) (using the dominant and non-dominant hand) were administered by a trained physician, who also instructed the subjects about test self-administration. The correlation and agreement, between the guided and self-administered tests were assessed with Pearson and Spearman coefficients and the Bland-Altman method. Results. Thirty-eight healthy volunteers were included. The median age was 36 (range: 23-55) years old, and 55.26% were female. The correlation coefficient between guided and selfadministered tests was 0.37 for the T25-FWT (p=0.01), 0.54 for the SDMT (p<0.001), and 0.64 and 0.65 for the 9-HPT, in the dominant and non-dominant hands, respectively (p<0,001). Both forms of administration were concordant for the T25-FWT (95%CI: -1,49 to 1,43), the 9-HPT with dominant hand (95%CI: -5,23 to 4,09), the 9-HPT with non-dominant hand (95%CI: -7,75 to 7,14) and the SDMT (95% CI: -20,94 to 24,10). Conclusions. We provide a proof of concept related to the feasibility of the selfadministration of the T25-FWT, the 9-HPT, and the SDMT, as a tool to improve monitoring in routine clinical practice.

In Vitro and In Silico Study on the Impact of Chlorogenic Acid in Colorectal Cancer Cells: Proliferation, Apoptosis, and Interaction with ß-Catenin and LRP6.

Colorectal cancer mortality rate and highly altered proteins from the Wnt/ß-catenin pathway increase the scientific community's interest in finding alternatives for prevention and treatment. This study aims to determine the biological effect of chlorogenic acid (CGA) on two colorectal cancer cell lines, HT-29 and SW480, and its interactions with ß-catenin and LRP6 to elucidate a possible modulatory mechanism on the Wnt/ß-catenin pathway. These effects were determined by propidium iodide and DiOC6 for mitochondrial membrane permeability, MitoTracker Red for mitochondrial ROS production, DNA content for cell distribution on cell cycle phases, and molecular docking for protein-ligand interactions and binding affinity. Here, it was found that CGA at 2000 µM significantly affects cell viability and causes DNA fragmentation in SW480 cells rather than in HT-29 cells, but in both cell lines, it induces ROS production. Additionally, CGA has similar affinity and interactions for LRP6 as niclosamide but has a higher affinity for both ß-catenin sites than C2 and iCRT14. These results suggest a possible modulatory role of CGA over the Wnt/ß-catenin pathway in colorectal cancer.