Progressive plasticity during colorectal cancer metastasis.

Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 + intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.

SARS-CoV-2 seroprevalence in workers from a Colombian University Hospital.

BACKGROUND: Antibody (Ab) tests for SARS-CoV-2 virus allows for the estimation of incidence, level of exposure and duration of immunity acquired by a previous infection. In health workers, the hospital setting might convey a greater risk of infection. AIMS: To describe the frequency of immunoglobulin G (IgG) Abs (IgG-Abs) to the SARS-CoV-2 virus among workers at a third-level university hospital in Colombia. METHODS: In this cross-sectional study, we included medical and non-medical personnel with at least one real-time polymerase chain reaction (RT-PCR)/antigen test between March 2020 and March 2021. In April 2021, an IgG-Ab test against SARS-CoV-2 was conducted for all participants and replicated 2 weeks later in a random sample (10%). The frequency of IgG-Abs is presented based on status (positive/negative) and time elapsed since RT-PCR/antigen test (<3 months, 3-6 months, >6 months). RESULTS: We included 1021 workers (80% women, median age 34 years (interquartile range 28-42), 73% medical personnel, 23% with previous positive RT-PCR/antigen). The overall seroprevalence was 35% (95% CI 31.6-37.4, 35% in medical and 33% in non-medical personnel). For those with a previous positive RT-PCR/antigen test, the seroprevalence was 90% (<3 months), 82% (3-6 months) and 48% (>6 months). In participants with a previous negative RT-PCR/antigen test, the seroprevalence was 17% (<3 months), 21% (3-6 months) and 29% (>6 months). CONCLUSIONS: High IgG-Ab positivity was found in hospital personnel, regardless of work activities. The prevalence of detectable Abs differed by previous RT-PCR/antigen status and time elapsed since the diagnostic test.

[Efficacy of tele-rehabilitation in patients with chronic obstructive pulmonary disease: a systematic review].

The COVID-19 pandemic has required the use of new technologies to carry out rehabilitation sessions for COP D remotely. The aim of this systematic review was to analyse the available evidence on the efficacy of telerehabilitation in COPD patients. PubMed, WOS, PEDro and Cochrane databases were consulted. The systematic review included nine clinical trials, 55.5% of which display good methodological quality. The most commonly used rehabilitation methods were applications or software for real-time video-calls, visualisation of exercises and recording progress. TR was as effective as outpatient pulmonary rehabilitation, with greater benefits in functional capacity, self-efficacy, mental health, exacerbations and emergency care visits, offering a cost-effective option with high patient satisfaction. The small number of studies and the variety of rehabilitation methods examined limit the value of the evidence obtained.

Alimentación funcional para corregir desórdenes gastrointestinales asociados a trastornos del espectro autista: una revisión sistemática / Functional feeding to correct gastrointestinal disorders associated with autism spectrum disorders: a systematic review

Antecedentes: los trastornos gastrointestinales (TGI) son comorbilidades comunes en los pacientes con trastornos del espectro autista (TEA); los tratamientos con dietas libres de gluten y caseína (LGLC) o suplementos de prebióticos/probióticos podrían reducir la severidad de los TGI. Objetivo: integrar y discutir la evidencia sobre la efectividad de las terapias con dietas LGLC y suplementos de prebióticos/probióticos sobre los TGI en pacientes con TEA. Metodología: se utilizaron las guías para la publicación de revisiones sistemáticas y metaanálisis (PRISMA). Se analizaron las características de los participantes, las intervenciones dietéticas, la administración de suplementos de prebióticos/prebióticos, los efectos de las intervenciones sobre los TGI, el riesgo de sesgo de los estudios y la seguridad de los tratamientos. Resultados: se analizaron quince investigaciones; la prevalencia de los TGI entre los pacientes con TEA fue alta (58 %; rango, 27-83 %). En más del 20 % de los pacientes intervenidos con dietas LGLC o suplementos disminuyó la severidad de los TGI (principalmente estreñimiento, diarrea y dolor abdominal). Se reportaron aumentos en los conteos de bacterias benéficas y una disminución de la proporción de bacterias patógenas tras el uso de los suplementos. Sin embargo, todas estas investigaciones presentaron sesgos metodológicos importantes. Conclusiones: aunque se han encontrado reducciones en la frecuencia y severidad de algunos TGI, la efectividad de estos tratamientos aún no se ha comprobado. Dadas las diferencias metodológicas de las investigaciones, se justifica el diseño de estudios rigurosos para evaluar los efectos terapéuticos de estos tratamientos sobre la salud gastrointestinal en pacientes con TEA (AU)

Background: gastrointestinal disorders (GIDs) are common comorbidities in patients with autism spectrum disorders (ASD); treatments with gluten- and casein-free (LGLC) diets or prebiotic/probiotic supplements may reduce the severity of GIDs. Objective: to integrate and discuss the evidence on the effectiveness of LGLC diet therapies and prebiotic/probiotic supplements on GIDs in patients with ASD. Methodology: the guidelines for the publication of systematic reviews and meta-analyses (PRISMA) were used. Participant characteristics, dietary interventions, prebiotic/prebiotic supplementation, effects of interventions on GIDs, risk of bias, and safety of treatments were analyzed. Results: fifteen investigations were analyzed; the prevalence of GIDs among patients with ASD was high (58 %; range, 27-83 %). In more than 20 % of the patients managed with LGLC diets or supplements GID severity decreased (mainly constipation, diarrhea, and abdominal pain). Increases in the counts of beneficial bacteria and a decrease in the proportion of pathogenic bacteria were reported after supplement use. However, all these investigations had significant methodological biases. Conclusions: although reductions in the frequency and severity of some GIDs have been found, the effectiveness of these treatments has not been proven yet. Given the methodological differences in the investigations, the design of rigorous studies to evaluate the therapeutic effects of these treatments on gastrointestinal health in patients with ASD is warranted (AU)

Estudios mamográficos en un centro metropolitano de referencia en imágenes mamarias: Chile 2008-2018 ¿Vamos por el camino correcto? / Analysis of mammograms performed in a public imaging center in Santiago, Metropolitan Region Chile 2008-2018

BACKGROUND: Mammograms are one of the most effective preventive means for the early detection of breast cancer. OBJECTIVE: To describe the features of patients and results of mammograms performed at a public breast imaging service of the Santiago Metropolitan Area. MATERIAL AND METHODS: We reviewed the reports of mammograms performed on 174,017 women and 18 men, between 2008 and 2018 in an Imaging Center. The BI-RADS classification was used in the reports. RESULTS: Forty-six percent of mammograms (75,781) were reported as BI-RADS 2. The high proportion of BI-RADS 4 reports (674 reports) was seen in patients aged 40 to 49 years, corresponding to 30% of reports in this age range. Among patients aged 50 to 59 years, there were 779 BI-RADS 4 reports (35%). BI-RADS 5 reports were more common among patients aged 50 to 59 years (50 reports, 30%) and among patients aged 70 years or older (83 reports, 28%). CONCLUSIONS: The presence of a significant number of women between 40 and 49 years of age with a BI-RADS 4 mammography result stands out; being an opportunity to develop new clinical research and public health strategies within the framework of the Universal Health Care policy for breast cancer in Chile.

Eficacia de la tele-rehabilitación en pacientes con enfermedad pulmonar obstructiva crónica: una revisión sistemática / Efficacy of tele-rehabilitation in patients with chronic obstructive pulmonary disease: a systematic review

La pandemia de la COVID-19 ha requerido el uso de nuevas tecnologías para realizar las sesiones de rehabilitación en la EPOC de manera telemática. El objetivo de esta revisión sistemática fue analizar la evidencia disponible sobre la eficacia de la telerehabilitación en pacientes con EPOC. Se consultaron las bases de datos PubMed, WOS, PEDro y Cochrane. La revisión incluyó nueve ensayos clínicos, el 55,5% con buena calidad metodológica. Los métodos de telerehabilitación más utilizados fueron las aplicaciones o software para realizar video-llamadas a tiempo real, visualizar los ejercicios y registrar los progresos conseguidos. La telerehabilitación fue tan eficaz como la rehabilitación pulmonar ambulatoria, obteniendo mayores beneficios en capacidad funcional, autoeficacia, salud mental, exacerbaciones y visitas a urgencias, siendo una opción rentable y con alta satisfacción del paciente. El pequeño número de estudios y la variedad de métodos de telerehabilitación limitan el valor de la evidencia obtenida.(AU)

The COVID-19 pandemic has required the use of new technologies to carry out rehabilitation sessions for COP Dremotely. The aim of this systematic review was to analyse the available evidence on the efficacy of telerehabilitation in COPD patients. PubMed, WOS, PEDro and Cochrane data bases were consulted. The systematic review included nine clinical trials, 55.5% of which display good methodological quality. The most commonly used rehabilitation methods were applications or software for real-time video-calls, visualisation of exercises and recording progress. TR was as effective as outpatient pulmonary rehabilitation, with greater benefits in functional capacity, self-efficacy, mental health, exacerbations and emergency care visits, offering a cost-effective option with high patient satisfaction. The small number of studies and the variety of rehabilitation methods examined limit the value of the evidence obtained.(AU)

The role of afforestation species as a driver of Hg accumulation in organic horizons of forest soils from a Mediterranean mountain area in SW Europe.

Forest areas are a primary sink of atmospheric mercury (Hg) within terrestrial ecosystems, whereas forest vegetation plays a key role in atmospheric Hg transfer to soil horizons. This study assessed variations in total Hg contents (HgT) and accumulation (HgRes) in the soil organic horizons of a forest area in NE Portugal, where post-wildfire afforestation led to the substitution of the native deciduous species (Quercus pyrenaica) by fast-growing coniferous species (Pseudotsuga menziesii and Pinus nigra). The study also evaluated, for each species, the links between Hg contents and other biophilic elements of soil organic matter (C, N, S) present in organic subhorizons (OL, OF, OH). Mean HgT in the organic horizons of the different tree species follow the sequence: P. nigra (88 µg kg-1) < Q.pyrenaica (101 µg kg-1)

[Analysis of mammograms performed in a public imaging center in Santiago, Metropolitan Region Chile 2008-2018]. / Estudios mamográficos en un centro metropolitano de referencia en imágenes mamarias: Chile 2008-2018 ¿Vamos por el camino correcto?

BACKGROUND: Mammograms are one of the most effective preventive means for the early detection of breast cancer. OBJECTIVE: To describe the features of patients and results of mammograms performed at a public breast imaging service of the Santiago Metropolitan Area. MATERIAL AND METHODS: We reviewed the reports of mammograms performed on 174,017 women and 18 men, between 2008 and 2018 in an Imaging Center. The BI-RADS classification was used in the reports. RESULTS: Forty-six percent of mammograms (75,781) were reported as BI-RADS 2. The high proportion of BI-RADS 4 reports (674 reports) was seen in patients aged 40 to 49 years, corresponding to 30% of reports in this age range. Among patients aged 50 to 59 years, there were 779 BI-RADS 4 reports (35%). BI-RADS 5 reports were more common among patients aged 50 to 59 years (50 reports, 30%) and among patients aged 70 years or older (83 reports, 28%). CONCLUSIONS: The presence of a significant number of women between 40 and 49 years of age with a BI-RADS 4 mammography result stands out; being an opportunity to develop new clinical research and public health strategies within the framework of the Universal Health Care policy for breast cancer in Chile.

Cost-utility analysis of ceftazidime-avibactam versus colistin-meropenem in the treatment of infections due to Carbapenem-resistant Klebsiella pneumoniae in Colombia.

BACKGROUND: Ceftazidime-Avibactam (CAZ-AVI) is a new antimicrobial against carbapenem-resistant Klebsiella pneumoniae. The aim of the study is to examine the cost-effectiveness of CAZ-AVI compared to colistin-meropenem (COL+MEM) in Colombia. METHODS: A decision tree model was developed from health-care system perspective assuming a 30-day time horizon. The clinical course was simulated based on treatment response between 48 and 72 hours, and the duration of the treatment was 7-14 days. Cost inputs were extracted from a published Colombian manual tariffs and official databases, expressed in 2019 dollars (USD). RESULTS: In the base case analysis, CAZ-AVI was associated with reduced mortality, length of hospital stay and fewer add-on antibiotics, resulting in an increase of 1.76 QALYs per patient versus COL+MEM and incremental costs associated in CAZ-AVI were $2,521 higher per patient compared to COL+MEM ($755 versus $3,276). The incremental costs were partially increased due to the lower mortality rate observed with CAZ-AVI. The incremental cost-effectiveness ratio was estimated to be $3,317 per QALY. In the probabilistic sensitivity analysis, with a willingness to pay above $2,438, CAZ-AVI has higher probability of being cost-effective. CONCLUSION: CAZ-AVI demonstrates cost-effectiveness as a treatment for Carbapenem-resistant Klepsiella pneumoniae infections by reducing the number of deaths and increasing QALYs. EXPERT COMMENTARY: Previous studies and surveillance programs from Colombia have reported prevalence of pathogens and the antimicrobial susceptibility of infections caused by multidrug-resistant Gram-negative bacteria. The health authorities have to consider and plan adequate surveillance systems in order to predict the resistance type and in choose the optimal antibiotics when infections occur.

Severity and duration of allergic conjunctivitis: are they associated with severity and duration of allergic rhinitis and asthma?

Summary: Objective. The association of allergic conjunctivitis (AC) with rhinitis and/or asthma is poorly understood. The objective of this study was to apply the Consensus Document for Allergic Conjunctivitis (DECA) criteria for the classification of AC to a population of patients with AC to assess the association between the severity and duration of AC and rhinitis and/or asthma. Methods. Patients with ocular symptoms of AC who participated in the 'Alergológica 2015' study were included. The demographics, classification according to the DECA criteria, etiology, and comorbidities were evaluated by age groups (less or equal than 14 and greater than 14 years). Results. A total of 2,914 patients (age range, 1-90 years) were included in the "Alergológica 2015" study. Of these, 965 patients (33.1%) were diagnosed with AC (77.5% > 14 years). AC was classified as severe, moderate, or mild in 1.8%, 46.4%, and 51.8%, respectively; and as intermittent or persistent in 51.6% and 48.4% of the patients. AC alone occurred in 4% of patients. AC was mainly associated with rhinitis (88.4%), asthma (38.2%), food allergy (8.3%) and atopic dermatitis (3.5%). In allergic respiratory disease rhinitis preceded AC and asthma developed later. The severity and duration of AC was significantly associated with severity and duration of rhinitis (p less than 0.001 for both age groups) and asthma (p less than 0.001 only in adults). Conclusions. The application of the new DECA classification for AC reveals a direct relationship between AC, rhinitis and asthma respect to severity and duration. These relationships suggest that AC should be considered an integral part of the "one airway, one disease" hypothesis.

The Full Spectrum of COVID-19 Development and Recovery Among Kidney Transplant Recipients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) fatality rate is high among kidney transplant recipients. Among survivors, kidney outcomes, seroconversion, and persistence of viral shedding are unexplored. METHODS: Single-center prospective cohort study including data from kidney transplant recipients with confirmed COVID-19 between March 20, 2020 and July 31, 2020. Outcomes were adjudicated until August 31, 2020 or the date of death. RESULTS: There were 491 patients with COVID-19 among the 11 875 recipients in follow-up. The majority were middle aged with ≥1 comorbidities. Thirty-one percent were treated at home, and 69% required hospitalization. Among the hospitalized, 61% needed intensive care, 75% presented allograft dysfunction, and 46% needed dialysis. The overall 28-day fatality rate was 22% and among hospitalized patients it was 41%. Age (odds ratio, 3.08; 95% confidence interval, 1.86-5.09), diabetes mellitus (odds ratio, 1.69; 95% confidence interval, 1.06-2.72), and cardiac disease (odds ratio, 2.00; 95% confidence interval, 1.09-3.68) were independent factors for death. Among the 351 survivors, 19% sustained renal graft dysfunction, and there were 13 (4%) graft losses. Biopsy (n = 20) findings were diverse but decisive to guide treatment and estimate prognosis. Seroconversion was observed in 79% of the survivors and was associated with disease severity. Persistence of viral shedding was observed in 21% of the patients without detectable clinical implications. CONCLUSIONS: This prospective cohort analysis confirms the high 28-day fatality rate of COVID-19, associated primarily with age and comorbidities. The high incidence of allograft dysfunction was associated with a wide range of specific histologic lesions and high rates of sequelae and graft loss. Seroconversion was high and the persistence of viral shedding deserves further studies.

Utilidad de la ecografía diafragmática para predecir el éxito en la extubación / Usefulness of diaphragmatic ultrasound in predicting extubation success

Objetivo Evaluar la exactitud diagnóstica de la ecografía diafragmática para predecir el éxito en la extubación. Diseño Estudio de exactitud diagnóstica. Ámbito Unidad de Cuidado Intensivo Médico de un hospital académico de la ciudad de Bogotá (Colombia). Pacientes o participantes Muestra consecutiva de pacientes mayores de 18 años con ventilación mecánica invasiva durante más de 48h. Intervenciones Evaluación ecográfica diafragmática al finalizar la prueba de ventilación espontánea. Variables de interés principales Se evaluó la excursión diafragmática (ED, cm), el tiempo de inspiración (TPIAdia, s), la velocidad de contracción del diafragma (ED/TPIAdia, cm/s), el tiempo total (Ttot, s) y la fracción de engrosamiento (TFdi, %). Resultados Se incluyeron 84 pacientes, el 79,8% (n=67) con extubación exitosa y el 20,2% (n=17) con extubación fallida. La variable con mejor capacidad discriminatoria para predecir éxito en la extubación fue la velocidad de contracción, con un AUC-ROC de 0,70 (p=0,008). Conclusiones La velocidad de contracción diafragmática mostró una capacidad discriminatoria aceptable. La ultrasonografía podría formar parte de un abordaje multifactorial en el proceso de extubación. (AU)

Objective To evaluate the diagnostic accuracy of diaphragmatic ultrasound in predicting extubation success. Design A diagnostic accuracy study was carried out. Scope Intensive Care Unit of an Academic hospital in the city of Bogotá (Colombia). Patients or participants A consecutive sample of patients >18 years of age subjected to invasive mechanical ventilation for >48h. Interventions Diaphragmatic ultrasound evaluation at the end of spontaneous ventilation testing. Main variables of interest Diaphragmatic excursion (DE, cm), inspiration time (TPIAdia, s), diaphragm contraction speed (DE/TPIAdia, cm/s) and total time (Ttot, s) were evaluated, together with thickening fraction (TFdi, %). Results A total of 84 patients were included, 79.8% (n=67) with successful extubation and 20.2% (n=17) with failed extubation. The variable with the best discriminatory capacity in predicting extubation success was diaphragm contraction speed, with AUC-ROC 0.70 (p=0.008). Conclusions Diaphragm contraction speed exhibited acceptable discriminatory capacity. Ultrasound could be part of a multifactorial approach in the extubation process. (AU)

[Usefulness of diaphragmatic ultrasound in predicting extubation success]. / Utilidad de la ecografía diafragmática para predecir el éxito en la extubación.

OBJECTIVE: To evaluate the diagnostic accuracy of diaphragmatic ultrasound in predicting extubation success. DESIGN: A diagnostic accuracy study was carried out. SCOPE: Intensive Care Unit of an Academic hospital in the city of Bogotá (Colombia). PATIENTS OR PARTICIPANTS: A consecutive sample of patients >18 years of age subjected to invasive mechanical ventilation for >48h. INTERVENTIONS: Diaphragmatic ultrasound evaluation at the end of spontaneous ventilation testing. MAIN VARIABLES OF INTEREST: Diaphragmatic excursion (DE, cm), inspiration time (TPIAdia, s), diaphragm contraction speed (DE/TPIAdia, cm/s) and total time (Ttot, s) were evaluated, together with thickening fraction (TFdi, %). RESULTS: A total of 84 patients were included, 79.8% (n=67) with successful extubation and 20.2% (n=17) with failed extubation. The variable with the best discriminatory capacity in predicting extubation success was diaphragm contraction speed, with AUC-ROC 0.70 (p=0.008). CONCLUSIONS: Diaphragm contraction speed exhibited acceptable discriminatory capacity. Ultrasound could be part of a multifactorial approach in the extubation process.