Evidence of SARS-CoV-2 infection in companion animals from owners who tested positive for COVID-19 in the Valley of Mexico.

BACKGROUND: Little is known about the companion animals which tested positive in Mexico for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Due to this, it is that we have documented the infection of companion animals, via an exploratory approach in two localities of the Valley of Mexico, in which the companion animal owners tested positive for COVID-19. METHODS: Oropharyngeal and nasopharyngeal swabs were collected from 21 companion animals. Also, a Reverse-Transcription Quantitative Polymerase Chain Reaction was used to test five probes in three SARS-CoV-2 genes. More than one-third (5/14) of these samples were positive for SARS CoV-2 corresponding to dogs. RESULTS: This research translates into the first available report on companion animals with SARS-CoV-2 infection in the most populated area of Mexico. Samples were added chronologically to previous reports prepared in other areas of the country, from February through November 2022. CONCLUSION: Although SARS-CoV-2 infection in dogs is not as common as in other animals, our results suggest that it can be transmitted to dogs by their owners to a greater extent than previously reported.

Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country.

Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non-genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision-recall curve (AUC-PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC-PRC for the Baseline Model (0.44%, 95%CI 0.42-0.46) increased by 0.22 (95%CI 0.15-0.29) when non-genetic factors were included, and by 0.25 (95%CI 0.20-0.30) when incorporating non-genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104-131) decreased to 92 (95%CI 60-128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59-110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non-genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.

Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study.

BACKGROUND: High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population. PATIENTS AND METHODS: This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group. RESULTS: Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%. CONCLUSIONS: Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.

Kaposi's sarcoma with gastric and rectal involvement in HIV patient.

A 67-year-old man admitted due to dyspnea, violaceous skin lesions and normocytic anemia under study. During admission, the patient is diagnosed with HIV infection in the AIDS phase, in addition to Kaposi's sarcoma with cutaneous, multiple digestive (gastric and rectal) and probably pulmonary involvement. Kaposi's sarcoma is a tumor of vascular origin caused by the human herpes virus type 8. There are four variants, our patient corresponds to the variant related to AIDS. Gastrointestinal involvement presents varied symptoms and the endoscopic image is very characteristic, but as it is a tumor with submucosal involvement, it sometimes requires endoscopic ultrasound-guided biopsy to make the diagnosis. Treatment is based on antiretroviral therapy and systemic chemotherapy.

Incidence of COVID-19 in patients exposed to chloroquine and hydroxychloroquine: results from a population-based prospective cohort in Catalonia, Spain, 2020.

BackgroundSeveral clinical trials have assessed the protective potential of chloroquine and hydroxychloroquine. Chronic exposure to such drugs might lower the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or severe coronavirus disease (COVID-19).AimTo assess COVID-19 incidence and risk of hospitalisation in a cohort of patients chronically taking chloroquine/hydroxychloroquine.MethodsWe used linked health administration databases to follow a cohort of patients with chronic prescription of hydroxychloroquine/chloroquine and a control cohort matched by age, sex and primary care service area, between 1 January and 30 April 2020. COVID-19 cases were identified using International Classification of Diseases 10 codes.ResultsWe analysed a cohort of 6,746 patients (80% female) with active prescriptions for hydroxychloroquine/chloroquine, and 13,492 controls. During follow-up, there were 97 (1.4%) COVID-19 cases in the exposed cohort and 183 (1.4%) among controls. The incidence rate was very similar between the two groups (12.05 vs 11.35 cases/100,000 person-days). The exposed cohort was not at lower risk of infection compared with controls (hazard ratio (HR): 1.08; 95% confidence interval (CI): 0.83-1.44; p = 0.50). Forty cases (0.6%) were admitted to hospital in the exposed cohort and 50 (0.4%) in the control cohort, suggesting a higher hospitalisation rate in the former, though differences were not confirmed after adjustment (HR: 1·46; 95% CI: 0.91-2.34; p = 0.10).ConclusionsPatients chronically exposed to chloroquine/hydroxychloroquine did not differ in risk of COVID-19 nor hospitalisation, compared with controls. As controls were mainly female, findings might not be generalisable to a male population.

Age-Dependent Decline in Synaptic Mitochondrial Function Is Exacerbated in Vulnerable Brain Regions of Female 3xTg-AD Mice.

Synaptic aging has been associated with neuronal circuit dysfunction and cognitive decline. Reduced mitochondrial function may be an early event that compromises synaptic integrity and neurotransmission in vulnerable brain regions during physiological and pathological aging. Thus, we aimed to measure mitochondrial function in synapses from three brain regions at two different ages in the 3xTg-AD mouse model and in wild mice. We found that aging is the main factor associated with the decline in synaptic mitochondrial function, particularly in synapses isolated from the cerebellum. Accumulation of toxic compounds, such as tau and Aß, that occurred in the 3xTg-AD mouse model seemed to participate in the worsening of this decline in the hippocampus. The changes in synaptic bioenergetics were also associated with increased activation of the mitochondrial fission protein Drp1. These results suggest the presence of altered mechanisms of synaptic mitochondrial dynamics and their quality control during aging and in the 3xTg-AD mouse model; they also point to bioenergetic restoration as a useful therapeutic strategy to preserve synaptic function during aging and at the early stages of Alzheimer's disease (AD).

2014: WHO's 25th World No Tobacco Day Global Campaign.

BACKGROUND: Since 1988, WHO have celebrated and supported World No Tobacco Day (WNTD), linking each year to a different tobacco-related theme. New technologies and creative design have been used by WHO in order to adapt to the current trends and needs providing the public with visually attractive posters and brochures. METHODS: A review of World Health Organization (WHO) material on WNTD was made, every year themes and posters were collected and analysed to be presented in a comprehensive way. RESULTS: A systematic timeline and an infographic were designed, enclosing the themes of WNTD across the years. The evolution of WNTD themes was commented on with a historical approach. CONCLUSIONS: WNTD has evolved adapting to the current scenarios, and is a good example of a global communication campaign on public health awareness and prevention.

[Geographical distribution and habitat of Trochilidae (Aves) in the state of Guerrero, Mexico]. / Distribución geográfica y habitat de la familia Trochillidae (Aves) en el estado de Guerrero, México.

The distribution and abundance of species of Trochillidae family is usually influenced by the flowering and phenology of plants used as a feeding source, mainly in primary forest, so that changes in vegetation cover could impact their populations. We analyzed and characterized the geographical distribution and habitat for 22 species of resident hummingbirds in the state of Guerrero using the vegetation and the land use map of INEGI Series IV (2007-2010). Distribution models were generated with the Genetic Algorithm for Rule Set Production (GARP), using historical records of scientific collections and fieldwork (2001-2009), in combination with climatic and topographic variables. Of the 22 modeled species, six are endemic to Mexico, the same number of species found in a risk category. The highest concentration with regards to richness (14-20 species), endemism (5-6 species) and number of threatened species of hummingbirds (5-6 species) occurred in the biotic province of Sierra Madre del Sur. However, the potential distribution of most of the hummingbirds occurred in disturbed sites or agroecosystems, as a result of changes in land-use. For Campylopterus hemileucurus, Lamprolaima rhami and Heliomaster longisrostris, their potential distribution was highest in areas of primary vegetation. Areas of high hummingbirds presence do not coincide with the Important Bird Areas proposed for bird conservation in Guerrero, considering that, despite its diversity and its extreme popularity, from the conservation perspective hummingbirds have received relatively little attention.

Impact of Point-of-Care Implementation in Pharmacist-Run Anticoagulation Clinics Within a Community-Owned Health System: A Two-Year Retrospective Analysis.

BACKGROUND: Point-of-care (POC) testing devices allow laboratory monitoring to be performed in various settings and accessed immediately. OBJECTIVE: To evaluate the outcomes of monitoring anticoagulation patients in pharmacistmanaged, multicenter clinics utilizing i-STAT POC machines. METHODS: This study was a retrospective, multicenter chart review of 150 patients before and after implementation of the POC intervention for anticoagulation monitoring. Data collected included international normalized ratio (INR) results, indication for warfarin, minor and major bleeds, thromboembolic events, emergency room (ER) visits, and hospitalizations before and after i-STAT POC implementation. RESULTS: The time in therapeutic INR range (TTR) was significantly higher after i-STAT POC implementation than before implementation (60.4% ± 21.2% and 52.5% ± 21.5%, respectively; P = .0001). There were no reports of major bleeding during the study period. Twenty-three minor bleeds were reported after i-STAT POC implementation compared to 19 events before implementation (P < .0001). One thromboembolic event was reported after i-STAT POC implementation. There was a significant difference in the number of hospitalizations before i-STAT POC implementation as opposed to after implementation (2 and 0, respectively; P < .0001). There was also a significant increase in ER visits after i-STAT POC implementation (P < .0001). CONCLUSION: The results of the study indicate improvement in TTR in pharmacist-managed anticoagulation clinics by 7.8%. Although the use of the i-STAT POC machine detected an increase in minor bleeds, thromboembolic events, and ER visits, there was a decrease in hospitalization. The outcomes of this multicenter study indicate that implementation on this scale provides improvement in regard to safety and cost.

Baseline glycated hemoglobin levels are associated with duodenal-jejunal bypass liner-induced weight loss in obese patients.

INTRODUCTION: Endoscopic treatment with the duodenal-jejunal bypass liner (DJBL) leads to significant weight loss in obese patients. We sought to identify clinical factors associated with weight loss in obese patients treated with the DJBL for 1 year. METHODS: Subjects with morbid obesity were enrolled in a single-arm, open-label, prospective trial and implanted with the DJBL. Patient demographics along with baseline comorbidities, anthropometrics, and biochemical variables were selected for univariate and multivariate analysis. RESULTS: The DJBL was implanted in 79 subjects and 61 completed 12 months of follow-up. There were 18 early removals. Baseline mean age and body mass index (BMI) were 35.4 ± 9.7 years and 43 ± 5.6 kg/m(2), respectively. Forty-four (72 %) were women. This population included 22 subjects with type 2 diabetes (T2DM). Twelve months after treatment, patients had a mean excess body weight loss (%EBWL) of 46 ± 18 %. Univariate analysis identified that fasting glycemia (r (2) = -0.303, p < 0.013), insulin-resistance determined by HOMA-IR (r (2) = -0.457, p < 0.019), and glycated hemoglobin (HbA1c) (r (2) = -0.471, p < 0.013) were associated inversely with %EBWL at 1 year. In this cohort of patients, the multivariate analysis indicated that only baseline HbA1c levels were associated inversely with %EBWL after 1 year of treatment (ß adjusted coefficient -0.758, p < 0.016). Importantly, no differences at 1 year in %EBWL were observed between patients with or without T2DM (%EBWL T2D 46.7 ± 20 % vs. non-T2DM 46.8 ± 18.6 %, p = 0.988). CONCLUSIONS: This analysis indicates that higher baseline HbA1c levels are associated independently with diminished body weight loss in obese patients treated with the DJBL independent of their diabetic status. These results show that DJBL induces clinically significant weight loss in both T2DM and non-T2DM patients.

[Immunophenotyping by spectral cytometry reveals a profile of lymphopenia associated with deregulation with an increase in effector memory lymphocytes in a patient with a mutation in the ITPR3 gene]. / Inmunofenotipo por citometría espectral, revela un perfil de linfopenia asociado a desregulación con aumento de linfocitos de memoria efectora en paciente con mutación en el gen ITPR3.

BACKGROUND: Variants in intracellular calcium transport genes have been associated with syndromic immunodeficiencies with a SCID phenotype. CASE REPORT: Seven-year-old girl of non-consanguineous parents, in Cartagena-Colombia. At two months of age, he presented hematochezia and was diagnosed with alimentary proctolitis without improvement with restriction to milk, wheat and eggs, and malnutrition developed. At eight months, a colon biopsy shows chronic lymphoid hyperplasia, presenting with anemia, eosinophilia, but total and specific IgE to normal foods. After four years, the Immunology Service found her asymptomatic, nutritionally recovered and without allergic sensitization, but eosinophilia and elevated calprotectin persisted, suggesting an early-onset inflammatory bowel disease. Immunoglobulins were normal, lymphocyte populations with CD3, CD4 and CD8 lymphopenia. At six years old, she presented atopic dermatitis, still had elevated calprotectin and was lymphopenic. Immunophenotyping by spectral cytometry using Cytek®cFluor®Immunoprofiling-Kit14 showed lymphopenia and CD4/CD8 inversion. Naïve CD4+ and CD8+ T lymphocytes were decreased, while T-CD8+CD45RA-CCR7- and T-CD8+CD45RA+CCR7- effector memory populations were expanded. Effector and central memory CD4+ T-lymphocytes were also increased1 (Image 1). The exome revealed a heterozygous variant in the ITPR3 gene (carrier father), c.7571G>A, p.(Arg2524His); predictors classify it as having a potential eliminating effect. CONCLUSIONS: The clinical features and immunophenotype of this candidate variant differ from others related to intracellular calcium transport. They are functional studies necessary to validate their causality. A patient with a potentially deleted variant presents an immunophenotype with CD3 lymphopenia and persistent lymphocyte activation.

ANTECEDENTES: Las variantes en genes del transporte de calcio intracelular han sido asociadas a inmunodeficiencias sindrómicas con un fenotipo IDCG. REPORTE DE CASO: Niña de siete años, de padres no consanguíneos, en Cartagena-Colombia. A los dos meses de vida, presenta hematoquecia y se diagnostica con proctolitis alimentaria sin mejoría con restricción a leche, trigo y huevo, desarrollando desnutrición. A los ocho meses, una biopsia de colon muestra hiperplasia linfoide crónica, cursa con anemia, eosinofilia, pero IgE total y específica a alimentos normales. A los cuatro años, el Servicio de Inmunología la encuentra asintomática, recuperada nutricionalmente y sin sensibilización alérgica, pero persiste eosinofilia y calprotectina elevada, sugiriendo una enfermedad inflamatoria intestinal de inicio temprano. Las inmunoglobulinas fueron normales, poblaciones linfocitarias con linfopenia CD3, CD4 y CD8. A los seis años, presenta dermatitis atópica, sigue con calprotectina elevada y linfopénica. El inmunofenotipo por citometría espectral mediante Cytek®cFluor®Immunoprofiling-Kit14, mostró linfopenia e inversión CD4/CD8. Los linfocitos T-vírgenes CD4+ y CD8+ estaban disminuidos, en cambio las poblaciones de memoria efectora T-CD8+CD45RA-CCR7- y T-CD8+CD45RA+CCR7­ estaban expandidas. Los linfocitos T-CD4+ de memoria efectora y central, también estaban aumentados1 (Imagen 1). El exoma reveló una variante heterocigótica en el gen ITPR3 (padre portador), c.7571G>A, p.(Arg2524His); los predictores la clasifican como de potencial efecto deletéreo. CONCLUSIONES: La clínica y el inmunofenotipo de esta variante candidata difiere de otras relacionadas con el transporte del calcio intracelular. Son necesarios estudios funcionales para validar su causalidad. Una paciente con una variante potencialmente deletérea, presenta un inmunofenotipo con linfopenia CD3 y activación persistente de los linfocitos.

[Lifestyle modification and risk factor control in the prevention and treatment of atrial fibrillation]. / Modificaciones en el estilo de vida y control de los factores de riesgo en la prevención y el tratamiento de la fibrilación auricular.

Atrial fibrillation (AF) is the most prevalent arrhythmia and is related with significant morbidity, mortality and costs. In spite of relevant advances in the prevention of embolic events and rhythm control, little has been done to reduce its prevalence, progression and impact, since it increases with ageing as well as with common risk factors such as alcohol intake, tobacco use and stress as well as with arterial hypertension, diabetes mellitus, heart failure, sleep apnea, kidney failure, chronic pulmonary obstructive disease, ischemic heart disease and stroke, among other important comorbidities. Fortunately, new evidence suggests that lifestyle modifications and adequate risk factors and comorbidities control could be effective in primary and secondary AF prevention, especially in its paroxysmal presentations. This is why a multidisciplinary approach integrating lifestyle modifications, risk factors and comorbidities control, is necessary in conjunction with rhythm or rate control and anticoagulation. Unfortunately, that holistic approach strategy is not considered, is scarcely studied or is subtilized in general clinical practice. The present statement's objectives are to: 1) review the relationship between habits, risk factors and illnesses with AF, 2) review the individual and common physiopathology mechanisms of each one of those conditions that may lead to AF, 3) review the effect of control of habits, risk factors and co-morbidities on the control and impact of AF, and 4) supply guidelines and recommendations to start multidisciplinary and integrative AF treatment.

La fibrilación auricular (FA) es la arritmia más frecuente y se asocia con importante morbilidad, mortalidad y costos. A pesar de los grandes avances en la prevención de eventos embólicos y en el control del ritmo, poco se ha realizado para reducir su prevalencia, progresión e impacto, debido a que incrementa con la edad y con la presencia de múltiples factores de riesgo muy comunes en la población, como obesidad, sedentarismo, alcoholismo, tabaquismo y estrés, así como con hipertensión arterial sistémica, diabetes mellitus, insuficiencia cardiaca, apnea del sueño, enfermedad renal crónica, enfermedad pulmonar obstructiva crónica, cardiopatía isquémica y enfermedad vascular cerebral, entre otra comorbilidad importante. Afortunadamente, nuevas evidencias demuestran que las modificaciones en el estilo de vida y el control adecuado de los factores de riesgo y de la comorbilidad pueden ser efectivos en la prevención primaria y secundaria de la FA, en especial en sus formas paroxísticas; para ello, es necesario un manejo multidisciplinario que integre las modificaciones en el estilo de vida, el manejo de los factores de riesgo y el control de la comorbilidad en el tratamiento de la FA en conjunto con el control del ritmo o de la frecuencia y la anticoagulación. Por desgracia, en la práctica clínica estas estrategias a menudo no se tienen en cuenta, son infrautilizadas y poco estudiadas. Los objetivos del presente posicionamiento son: 1) revisar la relación de los factores de riesgo y la comorbilidad con la FA, 2) revisar los mecanismos fisiopatológicos de cada una de estas condiciones, 3) revisar el impacto del control de los factores de riesgo y de la comorbilidad en el control y en el impacto de la FA, y 4) proporcionar guías y recomendaciones para la puesta en práctica de programas de tratamiento multidisciplinario e integral en pacientes con FA.

[Biogeographic regionalization of the mammals of tropical evergreen forests in Mesoamerica]. / Regionalización biogeográfica de la mastofauna de los bosques tropicales perennifolios de Mesoamérica.

Mesoamerica is a biologically complex zone that expands from Southern Mexico to extreme Northern Colombia. The biogeographical patterns and relationships of the mammalian fauna associated to the Mesoamerican Tropical Evergreen Forest (MTEF) are poorly understood, in spite of the wide distribution of this kind of habitat in the region. We compiled a complete georeferenced database of mammalian species distributed in the MTEF of specimens from museum collections and scientific literature. This database was used to create potential distribution maps through the use of environmental niche models (ENMs) by using the Genetic Algorithm for Rule-Set Production (GARP) using 22 climatic and topographic layers. Each map was used as a representation of the geographic distribution of the species and all available maps were summed to obtain general patterns of species richness in the region. Also, the maps were used to construct a presence-absence matrix in a grid of squares of 0.5 degrees of side, that was analyzed in a Parsimony Analysis of Endemicity (PAE), which resulted in a hypothesis of the biogeographic scheme in the region. We compiled a total of 41 527 records of 233 species of mammals associated to the MTEF. The maximum concentration of species richness (104-138 species) is located in the areas around the Isthmus of Tehuantepec, Northeastern Chiapas-Western Guatemala, Western Honduras, Central Nicaragua to Northwestern Costa Rica and Western Panama. The proposed regionalization indicates that mammalian faunas associated to these forests are composed of two main groups that are divided by the Isthmus of Tehuantepec in Oaxaca in: a) a Northern group that includes Sierra Madre of Chiapas-Guatemala and Yucatan Peninsula; and b) an austral group, that contains the Pacific slope of Chiapas towards the South including Central America. Some individual phylogenetic studies of mammal species in the region support the relationships between the areas of endemism proposed, which suggest a common biogeographical history. In spite that Mesoamerica is considered one of the most important hotspots for biological conservation, the poor knowledge of the biogeographic patterns, the scarcity of protected areas, and the high rate of habitat transformation due to human activities, make prioritary the development of conservation strategies that include patterns of species richness, endemism, and mammalian associations.

Nordihydroguaiaretic Acid Affects Undifferentiated and Differentiated Neuroblastoma Cells Differently through Mechanisms that Impact on Cell Viability.

AIM: We aimed to investigate the mechanisms involved in the neurotoxic effects of NDGA on differentiated and undifferentiated human neuroblastoma cells (MSN), assessing cell viability, changes in the actin cytoskeleton, cell migration and the expression of the 5-LOX enzyme and the inhibitor of cell cycle progression p21WAF1/CIP1. BACKGROUND: High expression and activity of the lipoxygenase enzyme (LOX) have been detected in several tumors, including neuroblastoma samples, suggesting the use of LOX inhibitors as potential therapy molecules. Among these, the natural compound nordihydroguaiaretic acid (NDGA) has been extensively tested as an antiproliferative drug against diverse types of cancer cells. OBJECTIVE: In this study, we analyzed the toxic effect of NDGA on neuroblastoma cells at a dose that did not affect cell survival when they differentiated to a neuron-like phenotype and the potential mechanisms involved in the anticancer properties. METHODS: We exposed human neuroblastoma cells (MSN) to different concentrations of NDGA before and after a differentiation protocol with retinoic acid and nerve growth factor and analyzed cell viability, cell migration, actin cytoskeleton morphology and the levels of the cell cycle inhibitor p21WAF1/CIP1 and 5-LOX. RESULTS: We found that differentiated human neuroblastoma cells are more resistant to NDGA than undifferentiated cells. The toxic effects of NDGA were accompanied by reduced cell migration, changes in actin cytoskeleton morphology, induction of p21WAF1/CIP1 and decreased levels of the 5- LOX enzyme. CONCLUSION: This study provides new evidence regarding the potential use of NDGA to induce cell death in human neuroblastoma.

Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: Real-life experience.

Background: Dupilumab is a treatment approved for uncontrolled moderate-to-severe atopic dermatitis (AD). Tropical and developing countries such as Colombia have characteristics that may impact the natural history of AD and access to medical treatments. In that sense, we aimed to describe the effectiveness and safety of dupilumab in adults with moderate to severe AD in a Colombian multicenter cohort. Methods: Multicenter descriptive study that included patients who started treatment between March 2018 and May 2020 in 6 centers. Disease severity was assessed using the following: Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). These measurements were collected according to availability at baseline, 3-5 months, 6-12 months, and more than 12 months. Days of sick leave, hospitalizations, and AD flares before and after dupilumab treatment were reported. Adverse events (AEs) were recorded during follow-up. Results: Ninety-three patients were included, with a median age of 32 years (IQR: 24.0; 40.0) and a disease evolution time of 21 years (IQR: 16.0; 29.5). 88.2% had at least 1 allergic disease other than AD. An improvement greater than or equal to 75% EASI was observed in 41.7% of patients at 3-5 months, in 73.7% of patients at 6-12 months, and in 75.0% of patients after 12 months. For those reporting SCORAD and POEM, the median percent change ([IQR], n) from baseline in SCORAD was -67.1 ([-79.2; -54.2], n = 16), -70.5 ([-85.8; -47.9], n = 36) and -66.7 ([-77.3; -51.0], n = 13); and POEM, -58.6 ([-66.4; -55.5], n = 4), -73.0 ([-86.5; -66.7], n = 16) and -87.3 ([-93.4; -69.6], n = 8), respectively. Before initiation of dupilumab treatment, 82 (88.2%) patients reported at least 1 flare of AD in the past 12 months. During the follow-up period, 30 (32.3%) patients reported at least 1 exacerbation or flare. Twelve patients (12.9%) presented an AE and 3 (3.2%) patients discontinued dupilumab for this cause. Conclusions: Dupilumab was effective and safe for the treatment of moderate to severe AD in point-of-care settings, with results similar to randomized controlled and other real-life studies. These positive results are still maintained even though a high number of patients had short interruptions in the use of dupilumab due to administrative problems.

Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers.

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10-5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate -0.006 kg/m2, 95% CI -0.009 to -0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.

Anatomic hepatectomy as a definitive treatment for hepatolithiasis: a cohort study.

BACKGROUND: Treatment requirements in hepatolithiasis may vary and may involve a multidisciplinary approach. Surgical resection has been proposed as a definitive treatment. OBJECTIVES: This study aimed to evaluate the clinical results of anatomic liver resection among Chilean patients with hepatolithiasis. METHODS: An historical cohort study was conducted. Patients who underwent hepatectomy as a definitive treatment for hepatolithiasis from January 1990 to December 2010 were included. Patients with a preoperative diagnosis of cholangiocarcinoma were excluded. Preoperative, operative and postoperative variables were evaluated. RESULTS: A total of 52 patients underwent hepatectomy for hepatolithiasis. The mean ± standard deviation patient age was 49.8 ± 11.8 years (range: 24-78 years); 65.4% of study subjects were female. A total of 75.0% of subjects had a history of previous cholecystectomy. The main presenting symptom was abdominal pain (82.7%). Hepatic involvement was noted in the left lobe in 57.7%, the right lobe in 34.6% and bilaterally in 7.7% of subjects. The rate of postoperative clearance of the biliary tree was 90.4%. Postoperative morbidity was 30.8% and there were no postoperative deaths. Three patients had recurrence of hepatolithiasis, which was associated with Caroli's disease in two of them. Overall 5-year survival was 94.5%. CONCLUSIONS: Anatomic liver resection is an effective treatment in selected patients with hepatolithiasis and is associated with low morbidity and no mortality. At longterm follow-up, anatomic hepatectomy in these patients was associated with a lower rate of recurrence.

Atrial fibrillation in Mexican population: Differences in presentation, comorbidities and risk factors between men and women / Fibrilación auricular en población mexicana: Diferencias en presentación, comorbilidades y factores de riesgo entre hombres y mujeres

OBJECTIVE: To know the epidemiological behavior and associations of AF in Mexican population. MATERIAL AND METHODS: 8,686 patients from 38 cardiologists participating in REMECAR were analyzed. They were divided by gender and age, the comorbidities studied were obesity, chronic kidney disease (CKD), high blood pressure (HBP), diabetes mellitus (DM), dyslipidemia,stroke, chronic obstructive pulmonary disease (COPD), hypothyroidism, heart failure (HF) and ischemicheart disease (IHD). Program used: IBM SPSS Statistic. RESULTS: AF was diagnosed in 498 patients (5.7%), with higher prevalence in men (6.1% vs. 5.3%) and older age in women (74.3 ± 12.1 vs. 70.5 + -12.3 years, p<0.0001). In those under 60 years, AF was associated in women with HF, in men with CKD, DM, stroke, hypothyroidism and HF. In women older than 60 years, AF was associated with CKD, dyslipidemia, stroke, chronic COPD and HF, in men with CKD, stroke, COPD, hypothyroidism, HF and IHD. AF in women increase the probability 1.13 for obesity, 1.13 for HBP, 2.8 for CKD, 2.9 for COPD, 4.3 for stroke and 6.5 for HF, in men increase the probability 1.05 for HBP, 1.4 for DM, 2.1 for CKD, 2.4 for COPD, 3.0 for hypothyroidism, 4.7 for stroke and 6.0 for HF. CONCLUSIONS: AF is a very common arrhythmia, with a higher prevalence in patients attending the cardiology consultation, in men and with an older age of presentation in women. The older the age, the higher the prevalence of AF and comorbidities, HF is the most frequent condition associated with AF.

OBJETIVO: Conocer el comportamiento epidemiológico y asociaciones de la FA en población mexicana. MATERIAL Y MÉTODOS: Analizamos 8,686 pacientes de 38 cardiólogos inscritos en REMECAR, divididos por edad y sexo. Comorbilidades estudiadas: obesidad, ERC, HTA, DM, dislipidemia, EVC, EPOC, hipotiroidismo, IC y CI. Programa: IBM SPSS. RESULTADOS: FA en 498 pacientes (5.7%), mayor prevalencia en hombres (6.1 vs. 5.3%), mayor edad en mujeres (74.3 ± 12.1 vs. 70.5 ± 12.3 años,p < 0.0001). En mujeres menores de 60 años la FA se asoció con IC (p = 0.041), en hombres con ERC (p = 0.43), DM(p = 0.009), EVC (p = 0.001), hipotiroidismo (p = 0.001) e IC (p = 0.001). En mujeres mayores de 60 años se asoció conERC (p = 0.001), dislipidemia (p = 0.001), EVC (p = 0.001), EPOC (p = 0.001) e IC (p = 0.001), en hombres con ERC(p = 0.002), EVC (p = 0.001), EPOC (p = 0.002), hipotiroidismo (p = 0.002), IC (p = 0.001) y CI (p = 0.033). En mujeres la FA se asoció con 1.13 veces mayor probabilidad de obesidad, 1.13 de HTA, 2.8 de ERC, 2.9 de EPOC, 4.3de EVC y 6.5de IC, en hombres la FA se asoció con 1.05 veces mas probabilidad de HTA, 1.4 de DM, 2.1 de ERC, 2.4 de EPOC, 3 dehipotiroidismo, 4.7 de EVC y 6 de IC. CONCLUSIONES: La FA es una arritmia muy frecuente, con mayor prevalencia en pacientes que acuden a consulta de cardiología, en hombres y mayor edad de presentación en las mujeres. A mayor edad, mayor prevalencia de FA y de comorbilidades, la IC es la condición más frecuente con la que se asoció la FA.

Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression.

Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence "gallstones → dysplasia → GBC". In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p-value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p-value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r2 = 0.26) and three cis-C22orf34-eQTLs (r2 = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR = 1.25 per log2 expression unit, 95% CI 1.04-1.52, p-value = 0.02). Our results suggest that preselection of lncRNAs based on tissue samples and exploitation of cis-lncRNA-eQTLs may facilitate the identification of circulating noncoding RNAs linked to cancer risk.

Surveillance for invasive meningococcal disease in children, US-Mexico border, 2005-2008.

We reviewed confirmed cases of pediatric invasive meningococcal disease in Tijuana, Mexico, and San Diego County, California, USA, during 2005-2008. The overall incidence and fatality rate observed in Tijuana were similar to those found in the US, and serogroup distribution suggests that most cases in Tijuana are vaccine preventable.