The Microbiota in Cancer: A Secondary Player or a Protagonist?

The intestinal microbiota and the human body are in a permanent interaction. There is a symbiotic relationship in which the microbiota plays a vitally important role in the performance of numerous functions, including digestion, metabolism, the development of lymphoid tissue, defensive functions, and other processes. It is a true metabolic organ essential for life and has potential involvement in various pathological states, including cancer and pathologies other than those of a digestive nature. A growing topic of great interest for its implications is the relationship between the microbiota and cancer. Dysbiosis plays a role in oncogenesis, tumor progression, and even the response to cancer treatment. The effect of the microbiota on tumor development goes beyond a local effect having a systemic effect. Another aspect of great interest regarding the intestinal microbiota is its relationship with drugs, modifying their activity. There is increasing evidence that the microbiota influences the therapeutic activity and side effects of antineoplastic drugs and also modulates the response of several tumors to antineoplastic therapy through immunological circuits. These data suggest the manipulation of the microbiota as a possible adjuvant to improve oncological treatment. Is it possible to manipulate the microbiota for therapeutic purposes?

Epstein­Barr virus as a promoter of tumorigenesis in the tumor microenvironment of breast cancer (Review).

Epstein­Barr virus (EBV) is an oncovirus associated with various neoplasms, including breast cancer (BC). EBV­associated oncogenesis requires the action of several viral molecules, such as EBV nuclear antigen 3C, latent membrane protein 1, microRNAs and long non­coding RNAs, which are able of manipulating the cellular machinery, inducing an evasion of the immune system, blocking apoptosis processes, promoting cell survival and metastasis. The risk of developing cancer is associated with epigenetic alterations and alterations in various signaling pathways. The activation of all these molecules can modify the expression of EBV proteins with oncogenic activity, influencing the oncogenic process. It is clear that BC, being multifactorial, presents a greater complexity; in numerous cases, the infection associated with EBV may be crucial for this neoplasia, if particular conditions for both the virus and host are present. In the present review, all these variables are analyzed in an aim to improve the understanding of the participation of EBV in BC.

Tumor response to neoadjuvant chemotherapy in molecular breast cancer subtypes in Medellin, Colombia. Retrospective cohort study / Respuesta tumoral a la quimioterapia neoadyuvante en subtipos moleculares de cáncer de mama en Medellín, Colombia. Estudio de cohorte retrospectivo

Objectives: To describe the frequency of clinical and pathological response in different molecular subtypes of breast cancer, in patients receiving prior neoadjuvant chemotherapy. Materials and methods: Descriptive retrospective cohort. The study population consisted of women 18 years of age and older with a histological diagnosis of invasive breast cancer stages IIA, IIB, IIIA, IIIB and IIIC, with a classification by molecular subtypes, who had received prior neoadjuvant chemotherapy, seen at a high complexity clinic in Medellin (Colombia), between July 1, 2017, and July 30, 2019. We measured age clinical stage, histological characteristics, molecular classification, and complete clinical and pathological responses by molecular subtype. A descriptive analysis was conducted. Results: Overall, 255 patients met the inclusion criteria. Mean age was 55.2 years; the clinical stages with the highest prevalence were IIIB (28.6 %) and IIB (26.3 %), and the most frequent by histologic grading were grades 3 (48.2 %) and 2 (37.3 %). Frequency by molecular types was as follows: luminal A (10.2 %), HER2-negative luminal B (39.6 %), triple-negative (23.1%), HER2-positive luminal B (13.7 %), and pure HER2 (13.3 %). Complete clinical response following chemotherapy, by molecular type, was as follows: luminal A (26.9 %), HER2-negative luminal B (37.6 %), HER2-positive luminal B (48.6 %), pure HER2 (41.2 %), triple-negative (45.8 %). Complete pathological response by molecular subtype was achieved in the luminal A (19.2 %), HER2-negative luminal B (32.7 %), HER2-positive luminal B (54.3 %), pure HER2 (50 %) and triple-negative (42.4 %) subtypes. Conclusions: In clinical practice, breast cancer classification by molecular subtypes is a means to approach the assess the to neoadjuvant chemotherapy. Prospective studies are needed in the region in order to determine the ability to predict overall and disease-free survival based on the complete pathologic response.

Objetivos: describir la frecuencia de la respuesta clínica y patológica, entre los diferentes subtipos moleculares de cáncer de mama, en pacientes que previamente recibieron quimioterapia neoadyuvante. Materiales y métodos: cohorte retrospectiva, descriptiva. Se incluyeron mujeres mayores de 18 años, con diagnóstico histológico de carcinoma invasivo de mama, en estadios IIA, IIB, IIIA, IIIB y IIIC, con clasificación por subtipos moleculares, que hubieran recibido quimioterapia neoadyuvante, atendidas en una clínica de alto nivel de complejidad localizada en Medellín (Colombia), entre el 1 de julio de 2017 y el 30 de julio de 2019. Las variables recolectadas fueron edad, estadio clínico, características histológicas, clasificación molecular y la respuesta clínica y patológica completa por subtipo molecular. Se realizó análisis descriptivo. Resultados: 255 pacientes cumplieron con los criterios de inclusión. La edad media fue de 55,2 años; los estadios clínicos con mayor prevalencia fueron IIIB (28,6 %) y IIB (26,3 %), respecto al grado histológico, los más frecuentes fueron grado 3 (48,2%) y 2 (37,3%). La frecuencia por subtipos moleculares fue: luminal A (10,2 %), luminal B HER2 negativo (39,6%), triple negativo (23,1 %), luminal B HER2 positivo (13,7 %), y HER2 puro (13,3%). La respuesta clínica completa posquimioterapia por subtipo molecular fue: luminal A (26,9 %), luminal B HER2 negativo (37,6 %), luminal B HER2 positivo (48,6 %), HER2 puro (41,2%), triple negativo (45,8%); se logró respuesta patológica completa por subtipo molecular, así: luminal A (19,2 %), luminal B HER2 negativo (32,7%), luminal B HER2 positivo (54,3 %), HER2 puro (50 %), triple negativo (42,4%). Conclusiones: en la práctica clínica, la clasificación por subtipos moleculares en cáncer de mama permite hacer una aproximación a la respuesta de la quimioterapia neoadyuvante. Se requieren estudios prospectivos en la región para determinar la capacidad predictiva de la respuesta patológica completa respecto a la sobrevida global y libre de enfermedad.

Respuesta tumoral a la quimioterapia neoadyuvante en subtipos moleculares de cáncer de mama en Medellín, Colombia. Estudio de cohorte retrospectivo / Tumor response to neoadjuvant chemotherapy in molecular breast cancer subtypes in Medellin, Colombia. Retrospective cohort study

Objetivos: Describir la frecuencia de la respuesta clínica y patológica, entre los diferentes subtipos moleculares de cáncer de mama, en pacientes que previamente recibieron quimioterapia neoadyuvante. Materiales y métodos: Cohorte retrospectiva, descriptiva. Se incluyeron mujeres mayores de 18 años, con diagnóstico histológico de carcinoma invasivo de mama, en estadios IIA, IIB, IIIA, IIIB y IIIC, con clasificación por subtipos moleculares, que hubieran recibido quimioterapia neoadyuvante, atendidas en una clínica de alto nivel de complejidad localizada en Medellín (Colombia), entre el 1 de julio de 2017 y el 30 de julio de 2019. Las variables recolectadas fueron edad, estadio clínico, características histológicas, clasificación molecular y la respuesta clínica y patológica completa por subtipo molecular. Se realizó análisis descriptivo. Resultados: 255 pacientes cumplieron con los criterios de inclusión. La edad media fue de 55,2 años; los estadios clínicos con mayor prevalencia fueron IIIB (28,6 %) y IIB (26,3 %), respecto al grado histológico, los más frecuentes fueron grado 3 (48,2 %) y 2 (37,3 %). La frecuencia por subtipos moleculares fue: luminal A (10,2 %), luminal B HER2 negativo (39,6 %), triple negativo (23,1 %), luminal B HER2 positivo (13,7 %), y HER2 puro (13,3 %). La respuesta clínica completa posquimioterapia por subtipo molecular fue: luminal A (26,9 %), luminal B HER2 negativo (37,6 %), luminal B HER2 positivo (48,6 %), HER2 puro (41,2 %), triple negativo (45,8 %); se logró respuesta patológica completa por subtipo molecular, así: luminal A (19,2 %), luminal B HER2 negativo (32,7 %), luminal B HER2 positivo (54,3 %), HER2 puro (50 %), triple negativo (42,4 %). Conclusiones: En la práctica clínica, la clasificación por subtipos moleculares en cáncer de mama permite hacer una aproximación a la respuesta de la quimioterapia neoadyuvante. Se requieren estudios prospectivos en la región para determinar la capacidad predictiva de la respuesta patológica completa respecto a la sobrevida global y libre de enfermedad.

Objectives: To describe the frequency of clinical and pathological response in different molecular subtypes of breast cancer, in patients receiving prior neoadjuvant chemotherapy. Materials and methods: Descriptive retrospective cohort. The study population consisted of women 18 years of age and older with a histological diagnosis of invasive breast cancer stages IIA, IIB, IIIA, IIIB and IIIC, with a classification by molecular subtypes, who had received prior neoadjuvant chemotherapy, seen at a high complexity clinic in Medellin (Colombia), between July 1, 2017, and July 30, 2019. We measured age clinical stage, histological characteristics, molecular classification, and complete clinical and pathological responses by molecular subtype. A descriptive analysis was conducted. Results: Overall, 255 patients met the inclusion criteria. Mean age was 55.2 years; the clinical stages with the highest prevalence were IIIB (28.6 %) and IIB (26.3 %), and the most frequent by histologic grading were grades 3 (48.2 %) and 2 (37.3 %). Frequency by molecular types was as follows: luminal A (10.2 %), HER2-negative luminal B (39.6 %), triple-negative (23.1%), HER2-positive luminal B (13.7 %), and pure HER2 (13.3 %). Complete clinical response following chemotherapy, by molecular type, was as follows: luminal A (26.9 %), HER2-negative luminal B (37.6 %), HER2-positive luminal B (48.6 %), pure HER2 (41.2 %), triple-negative (45.8 %). Complete pathological response by molecular subtype was achieved in the luminal A (19.2 %), HER2-negative luminal B (32.7 %), HER2-positive luminal B (54.3 %), pure HER2 (50 %) and triple-negative (42.4 %) subtypes. Conclusions: In clinical practice, breast cancer classification by molecular subtypes is a means to approach the assess the to neoadjuvant chemotherapy. Se requieren estudios prospectivos en la región para determinar la capacidad predictiva de la respuesta patológica completa respecto a la sobrevida global y libre de enfermedad.

Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis.

FAM20C (family with sequence similarity 20, member C) is a serine/threonine-specific protein kinase that is ubiquitously expressed and mainly associated with biomineralization and phosphatemia regulation. It is mostly known due to pathogenic variants causing its deficiency, which results in Raine syndrome (RNS), a sclerosing bone dysplasia with hypophosphatemia. The phenotype is recognized by the skeletal features, which are related to hypophosphorylation of different FAM20C bone-target proteins. However, FAM20C has many targets, including brain proteins and the cerebrospinal fluid phosphoproteome. Individuals with RNS can have developmental delay, intellectual disability, seizures, and structural brain defects, but little is known about FAM20C brain-target-protein dysregulation or about a potential pathogenesis associated with neurologic features. In order to identify the potential FAM20C actions on the brain, an in silico analysis was conducted. Structural and functional defects reported in RNS were described; FAM20C targets and interactors were identified, including their brain expression. Gene ontology of molecular processes, function, and components was completed for these targets, as well as for potential involved signaling pathways and diseases. The BioGRID and Human Protein Atlas databases, the Gorilla tool, and the PANTHER and DisGeNET databases were used. Results show that genes with high expression in the brain are involved in cholesterol and lipoprotein processes, plus axo-dendritic transport and the neuron part. These results could highlight some proteins involved in the neurologic pathogenesis of RNS.

Predictors for limb amputation in war vascular trauma: A 20-years retrospective analysis from the Colombian armed conflict.

BACKGROUND: The Latin American military vascular trauma is virtually unknown. The aim of this study was to describe severe war vascular trauma during the last 20 years of the Colombian armed conflict, and to identify predictors of limb amputation. METHODS: Retrospective analysis of a follow-up cohort from 1999 to 2019 of patients with associated severe vascular injuries (ISS >15) in the Colombian armed conflict treated at the Hospital Militar Central. RESULTS: Out of 5948 patients, 243 had military vascular trauma with 430 vascular injuries. The most frequent trauma mechanisms were gunshot wounds (n = 153; 63%). The most common injured vessels were femoral. 24 (10%) patients required amputations. Mortality was 4.1%. Amputation was associated with arteriovenous lesions (RR 4.82, p = 0.025), compartment syndrome (RR 4.2, p = 0.007), arteriovenous femoropopliteal injuries (RR 3.5, p = 0.0026), multiple arterial injuries (RR 3.35, p = 0.0218), associated fractures (RR 3.1, p = 0.0032). CONCLUSIONS: Concomitant arteriovenous injuries in popliteal and femoropopliteal lesions, multiple arterial lesions, bone fractures, and compartment syndrome are associated with amputation in severe vascular injury.

Clinical outcomes of long-term corneas preserved frozen in Eusol-C used in emergency tectonic grafts.

To report the clinical results on the use of corneas frozen in Eusol-C as tectonic corneal grafts.Retrospective review of medical records of patients who received frozen corneas as emergency tectonic grafts from 2013 to 2020. Corneas had been stored in Eusol-C preservation media at - 78 °C for a mean time of 6.9 months. Diagnosis, transplant characteristics, microbial culture results, anatomic integrity, epithelial healing, neovascularization, transparency, infection and need for additional surgeries were registered. Fifty corneas were used in 40 patients (mean age 60.5 years, 20 males) with a median follow-up of 27.3 months after surgery. Need for tectonic graft was due to: perforation secondary to immune diseases (6, 12%), neurotrophic ulcer (11, 22%), trauma (3, 6%), corneal infection (11, 22%), chronic disorders of the ocular surface (9, 18%) and previous corneal graft failure (10, 22%). Mean size of grafts was 5.6 mm and 36 cases (72%) also received an amniotic membrane graft. Thirty-eight corneas achieved epithelization (76%), 25 (50%) were clear and 19 (38%) developed neovascularization. None of the corneas were rejected. Seventeen corneas (34%) failed: 7 (14%) due to reactivation of baseline disease and 10 (20%) due to primary graft failure. Four corneas (8%) had positive microbial cultures suggestive of contamination and 2 (4%) developed a cornea abscess non-related to a positive microbial culture. Long-term preservation of donor corneas in Eusol-C at - 78 °C is a viable technique to meet the needs of emergency grafts with minimal equipment.

Perfiles de expresión de los genes ERG11, MDR1 y AFR1 en Cryptococcus neoformans var. grubii aislados de pacientes con HIV / Gene expression profiles of ERG11, MDR1 y AFR1 in Cryptococcus neoformans var. grubbi isolated from HIV patients

Introducción. El fluconazol es el antifúngico más utilizado para la prevención y el tratamiento de infecciones causadas por el género Cryptococcus, agente etiológico de la criptococosis. La resistencia al fluconazol en los aislamientos de Cryptoccocus neoformans puede hacer fracasar el tratamiento y generar recaídas de la infección. Objetivo. Evaluar los perfiles de expresión de los genes AFR1, MDR1 y ERG11 en aislamientos clínicos de C. neoformans var. grubii, durante la respuesta in vitro a la inducción con fluconazol. Materiales y métodos. Se estudiaron 14 aislamientos de C. neoformans var. grubii provenientes de pacientes con HIV, de los cuales 6 eran sensibles al fluconaol y 8 presentaban sensibilidad disminuida. Los niveles de expresión de los genes ERG11, AFR1 y MDR1 se determinaron mediante PCR en tiempo real. Resultados. Los aislamientos resistentes al fluconazol mostraron sobreexpresión de los genes AFR1 y MDR1, mientras que la expresión de los fenotipos de resistencia evaluados se mantuvo homogénea en ERG11, en todos los aislamientos de C. neoformans var. grubii. Conclusiones. La sobreexpresión de los genes AFR1 y MDR1 que codifican las bombas de eflujo, contribuye a la resistencia al fluconazol en los aislamientos estudiados. Sin embargo, los patrones de resistencia que se registran en este hongo, sumado a los casos de recaídas en pacientes con HIV, no pueden atribuirse únicamente a los casos de resistencia por exposición al fármaco. Otros mecanismos podrían también estar involucrados en este fenómeno, como la resistencia emergente (resistencia mediante otros genes ERG) y la heterorresistencia, los cuales deben ser estudiados en estos aislamientos.

Introduction: Fluconazole is the most used antifungal drug for prevention and treatment of Cryptococcus spp. infections, the etiological agent of cryptococcosis. Resistance to fluconazole among Cryptococcus neoformans isolates can lead to treatment failure and generate relapses. Objective: To evaluate the expression profles of the AFR1, MDR1 and ERG11 genes in C. neoformans var. grubii clinical isolates during the in vitro response to fluconazole induction. Materials and methods: Fourteen C. neoformans var. grubii isolates recovered from HIV patients were studied, in which 6 showed sensitivities to fluconazole and 8 decreased sensitivity. The expression levels of ERG11, AFR1 and MDR1 genes were determined by real-time PCR from extracted mRNA. Results: AFR1 and MDR1 genes from C. neoformans var. grubii were overexpressed in fluconazole resistant isolates, whereas ERG11 maintains homogeneous expression in all the evaluated resistance phenotypes of C. neoformans var. grubii isolates. Conclusions: The overexpression of AFR1 and MDR1 genes, which codify for efflux pumps, contributes to fluconazole resistance in the studied isolates. However, the resistance patterns in this fungus and the relapse cases in HIV patients cannot be attributed solely to the exposure to the drug. Heteroresistance and the emerging resistance (resistance through other ERG genes), might be other mechanisms involved in this phenomenon, which must be studied in these isolations.

Análisis de conglomerado de cáncer infantil y su relación con proximidad a fuentes de contaminación industrial en el Área Metropolitana del Valle de Aburrá, 2000-2015

Objetivo: Este estudio evaluó el efecto de la proximidad a fuentes industriales de contaminación del aire sobre la aparición de clústeres de casos de cáncer infantil en el Área Metropolitana del Valle de Aburrá, del departamento de Antioquia, durante el período 2000-2015. Metodología: La información de casos de cáncer infantil en menores de 15 años residentes del área metropolitana se obtuvo del Registro Poblacional de Cáncer de Antioquia, de dicho periodo. Se identificaron 32 conglomerados industriales, a partir del inventario de la autoridad ambiental local. Se realizaron pruebas de escaneo circular de Kulldorf locales y focalizadas, para detectar clústeres de cáncer infantil en los municipios y alrededor de los conglomerados industriales respectivamente. Se usó un modelo de regresión multivariable ajustado por estrato socioeconómico, para evaluar el efecto de las variables espaciales. Resultados: La tasa de incidencia específica en el Valle de Aburrá para el periodo evaluado fue de 117,13 casos por millón de niños menores de 15 años. Las tasas de incidencia más altas se presentaron en los municipios de Medellín y Sabaneta. La prueba de Kulldorf identificó 12 clústeres espaciales y 8 espacio-temporales con significación estadística en 7 de los municipios, particularmente en Bello y Medellín. Las pruebas focalizadas identificaron clústeres alrededor de 20 conglomerados industriales. En los modelos multivariables, un conglomerado en Bello evidenció asociación estadísticamente significativa e inversa entre la incidencia y la distancia al conglomerado con direccionalidad sureste. Conclusión: Algunos conglomerados espacio-temporales de cáncer infantil en el Área Metropolitana del Valle de Aburrá entre 2000 y 2015 están relacionados con proximidad a fuentes industriales de contaminación del aire.

Objective: This study evaluated the effect of proximity to industrial sources of air pollution on the occurrence of clusters of childhood cancer cases in the Aburrá Valley Metropolitan Area, Department of Antioquia, during the 2000-2015 period. Methodology: The information on childhood cancer cases in children under 15 years of age residing in the metropolitan area was obtained from the Registro Poblacional de Cáncer de Antioquia (Antioquia Cancer Population Registry) for that period. 32 industrial clusters were identified based on the local environmental authority's inventory. Local and targeted Kulldorff's circular scan tests were performed to detect childhood cancer clusters in the municipalities and surrounding the industrial clusters, respectively. We used a multivariate regression model adjusted for socioeconomic strata to assess the effect of spatial variables. Results: The specific incidence rate in the Aburrá Valley for the evaluated period was 117.13 cases per million children under 15 years of age. The highest incidence rates occurred in the municipalities of Medellín and Sabaneta. The Kulldorff test identified 12 spatial clusters and 8 space-time clusters that were statistically significant in 7 municipalities, particularly in Bello and Medellín. The targeted tests identified childhood cancer clusters surrounding 20 industrial clusters. In multivariate models, an industrial cluster in Bello showed a statistically significant inverse association between incidence and distance from the industrial cluster toward the southeast. Conclusion: Some space-time childhood cancer clusters in the Aburrá Valley Metropolitan Area between 2000 and 2015 are related to proximity to industrial sources of air pollution.

Objetivo: Este estudo avaliou o efeito da proximidade a fontes industriais de poluição do ar sobre a aparição de agrupações de casos de câncer infantil na Área Metropolitana do Valle de Aburrá, do departamento de Antioquia, durante o período 2000-2015. Metodología: A informação de casos de câncer infantil em menores de 15 anos residentes da área metropolitana foi obtida do Registro Populacional de Câncer de Antioquia, de tal período. Foram identificados 32 conglomerados industriais, a partir do inventário da autoridade ambiental local. Foram realizados testes de varredura circular de Kulldorf locais e focalizados, para detectar agrupações de casos de câncer infantil nos municípios e ao redor dos conglomerados industriais, respectivamente. Foi usado um modelo de regressão multivariável ajustado por nivel socioeconômico, para avaliar o efeito das variáveis espaciais. Resultados: A taxa de incidência específica no Valle de Aburrá para o período avaliado foi de 117,13 casos por milhão de crianças menores de 15 anos. As maiores taxas de incidencia apresentaram-se nos municípios de Medellín e Sabaneta. O teste de Kulldorf identificou 12 agrupações de casos espaciais e 8 espaço-temporais com significação estatística em 7 dos municípios, particularmente em Bello e Medellín. As provas focalizadas identificaram agrupações de casos ao redor de 20 conglomerados industriais. Nos modelos multivariáveis, um conglomerado em Bello evidenciou associação estatisticamente significativa e inversa entre a incidência e a distância com o conglomerado orientado ao sudeste. Conclusão: Algumas agrupações de casos espaço-temporais de câncer infantil na Área Metropolitana do Valle del Aburrá entre 2000 e 2015 estão relacionadas com a proximidade a fontes industriais de poluição do ar.

NOTCH expression variability and relapse of breast cancer in high-risk groups.

BACKGROUND: In regards to breast cancer (BC), survival or disease-free periods are still compromised mainly in Triple Negative (TN) and HER2 tumors. The participation of estrogen receptor (ER) has been reported as crucial in the signaling pathways, including the NOTCH pathway. The study was aimed to evaluate the expression of NOTCH1 and NOTCH3 in BC and its relationship with the presence of ER, as well as with relapses. METHODS: NOTCH1 and NOTCH3 expression was evaluated in BC using Oncomine database, Breast Cancer Gene Expression Miner database and Kaplan Meier Plotter. Subsequently, detection of NOTCH1 and NOTCH3 in 100 paraffin-embedded BC samples from Mexican patients was achieved by immunohistochemistry (IHC) and RT-qPCR, a group of benign breast tumors were included as controls. Relapses were evaluated by BC subtypes and their relationship with NOTCH1 and NOTCH3 expression, as well as with ER expression. RESULTS: The analyses from public databases of TN and HER2 groups, which are estrogen receptor-negative (ERN), revealed NOTCH1 and NOTCH3 expression variability. The overexpression was associated with lower relapse-free survival (P = 0.00019). These data were concordant with results from tumor samples of patients included in this study, which showed overexpression of NOTCH1 and NOTCH3 in ERN tumors, as well as lower relapse-free survival (P < 0.0001). CONCLUSIONS: NOTCH1 and NOTCH3 were found to be overexpressed mainly in ERN tumors. HER2 and TN groups, are related to higher relapse rates. Therefore, anti-NOTCH therapy could be justified and implemented in conventional treatments of high-risk BC groups.

Dealing with Emotional Vulnerability and Anxiety in Nurses from High-Risk Units-A Multicenter Study.

Compassion fatigue and anxiety derived from continued exposure to trauma and death greatly impact nurses' quality of care and quality of life, increasing their desire to leave work. The aim of the study is to assess compassion fatigue and anxiety prevalence and their association with secondary variables. A multicenter, cross-sectional study in nurses from four high-risk units, Emergency, Intensive Care, Oncology, and Pediatrics, was carried out in 14 hospitals in Catalonia (Spain) between 2015 and 2016. The primary endpoints were compassion satisfaction and compassion fatigue (burnout and secondary traumatic stress), which were assessed by Professional Quality of Life (ProQOL), and anxiety, assessed with the State-Trait Anxiety Inventory (STAI). Multivariable logistic regression analyzed the association of sociodemographic, training, working, and psychological factors. Of a total of 1302 nurses, 18.6% presented low compassion satisfaction; 19.7%, high burnout; and 36.4%, high secondary traumatic stress. Trait anxiety scored high in 7.2%. Although compassion satisfaction was present, it did not protect sufficiently against the high level of compassion fatigue or anxiety present in nurses in all centers. The working conditions in the units and variables showed a strong association with nurses' desire to leave. This corroborates the global challenge of healthcare professionals' shortage. Participants expressed the need for better training in emotional management.

Impacts of COVID-19 pandemic and public policies on corneal transplantations in Brazil / Impactos da pandemia da COVID-19 e das políticas públicas nos transplantes de córnea no Brasil

ABSTRACT Purpose: The study aimed to evaluate the impact of coronavirus disease 2019 (COVID-19) pandemic and public policies on corneal donations and transplantations in Brazil and get reliable indicators to support effective measures for improving the system of obtaining, processing, distributing, using, and controlling donated ocular tissues. Methods: A questionnaire was applied by the Brazilian office of the Pan-American Association of Eye Banks (APABO) to Brazilian Eye Banks to collect data from January to August 2020 and generate reliable indicators about the impact of the COVID-19 pandemic on corneal donations and transplantations in Brazil. Results: Data from 37 Eye Banks showed that 76.1% of the 3,060 donations and 74.5% of the 3,167 transplants occurred in the pre-pandemic period. From the 6,052 processed corneas, 71.8% were provided for therapeutic purposes: 72.9% were transplanted, 26.1% ended up being discarded (45% of which qualified for optical transplantation), and 1% remained in stock in glycerin. Of the 1,706 corneas that could not be eligible for therapeutic use, 47.9% were excluded due to tissue conditions, 43.6% for serological reasons, 6.7% due to contraindications found in clinical history after retrieval, and 1.8% for other factors. Conclusions: The negative impact of the COVID-19 pandemic on corneal donations and transplantations in Brazil resulted from the recommendation of the Health Ministry to suspend the retrieval of ocular tissues from donors in cardiopulmonary arrest for almost six months. The indicators reveal the compelling requirement for updating both the classification and cornea provision criteria by the Eye Banks and improving the Brazilian corneal distribution system.

RESUMO Objetivos: Dimensionar o impacto da pandemia da COVID-19 nas doações e transplantes de córnea no Brasil e obter indicadores confiáveis para o embasamento de proposições de medidas efetivas para a manutenção e o aperfeiçoamento do sistema de obtenção, processamento, distribuição, utilização e controle dos tecidos oculares doados. Métodos: Um questionário foi enviado, pelo escritório Brasil da Associação Pan-Americana de Bancos de Olhos (APABO), aos Bancos de Olhos brasileiros. Dados de janeiro a agosto de 2020 foram coletados para gerar indicadores confiáveis sobre o impacto da pandemia da COVID-19 nas doações e transplantes de córnea no Brasil. Resultados: Dados de 37 Bancos de Olhos mostraram que 76,1% das 3.060 doações e 74,5% dos 3.167 transplantes aconteceram no período pré-pandemia. Das 6.052 córneas processadas 71,8% foram disponibilizadas para fins terapêuticos: 72,9% foram transplantadas, 26,1% acabaram sendo inviabilizadas (45% destas, classificadas para indicações ópticas) e 1%, em glicerina, permanecia em estoque. Das 1.706 córneas que não puderam ser disponibilizadas para uso terapêutico, 47,9% foram excluídas por fatores relacionados às condições dos tecidos, 43,6% por fatores sorológicos, 6,7% por contraindicações constatadas em histórico clínico após a captação e 1,8% por outros fatores. Conclusões: O impacto negativo da pandemia nas doações e transplantes de córnea no Brasil se deveu à recomendação do Ministério da Saúde de suspender, por quase seis meses, as captações de doadores em parada cardiorrespiratória. Os indicadores tornam evidente a necessidade de atualização dos critérios de classificação e disponibilização das córneas pelos Bancos de Olhos e do sistema nacional de distribuição destes tecidos.

Efficacy in size and symptom reduction of radiofrequency ablation of benign non-functioning thyroid nodules.

INTRODUCTION: Radiofrequency ablation (RFA) plays an increasing role in the management of thyroid nodules. The purpose of this study was to evaluate the safety and efficacy of RFA of benign thyroid nodules in terms of volume reduction and symptom relief. METHODS: We reviewed the medical records of patients with a solitary thyroid nodule who received RFA at our centre from April 2016 to January 2020. Ultrasound-guided RFA was performed by the moving-shot technique. Patients were followed up with ultrasound examinations and thyroid function tests. We evaluated changes in volume and in compressive (0-10 scale) and cosmetic (4-point scale) symptoms to analyse efficacy and complications, and in thyroid function to evaluate safety. RESULTS: A total of 72 patients were included in the study. The mean follow-up was 11.1±0.7 months. There was a statistically significant reduction in size of the nodules at Month 1, 3, 6 and 12 after RFA (expressed as volume reduction rate: 34%±2.1, 50.8%±2.2, 60.3%±2.6, 58.87%±3.5, p<0.0001). We found statistically significant improvement in compressive symptoms (from 7.1±0.26 to 1.76±0.33, p<0.0001) and in cosmetic alteration (from 3.66±0.09 to 2.14±0.14, p<0.0001). No major complications were observed. DISCUSSION: RFA achieved significant volume reduction and improved compressive symptoms as well as cosmetic complaints, with minimum side effects. Our results are in line with recent available evidence and further support the use of RFA as a safe and effective therapeutic option in the management of benign thyroid nodules.

Propiedades psicométricas de la versión corta del Inventario Friburgo de Mindfulness / Psychometric properties of the Freiburg Mindfulness Inventory short version

Resumen Antecedentes El mindfulness está cobrando un interés cada vez más creciente desde el ámbito de intervención psicológica, pero también desde ámbitos educativos o laborales. Este interés está suscitando, como consecuencia, la necesidad de disponer de herramientas que ayuden a medirlo. Objetivo Presentar las propiedades psicométricas de la versión corta de la adaptación española del Inventario Friburgo de Mindfulness (IFM) que tiene sus raíces teóricas en la tradición budista. Método Se contó con una muestra de 543 participantes (161 hombres y 379 mujeres) cuya edad media fue de 35.27 ( DT = 13.66), con unos niveles educativos y situaciones laborales heterogéneos. Resultados La consistencia interna ( α = .86, ω = .87) así como otros aspectos relacionados con la validez de constructo pueden considerarse apropiados. Los análisis factoriales exploratorios llevados a cabo apuntan a que los ítems de la escala se agrupan en dos factores relacionados, aceptación incondicional y atención plena, frente al modelo unifactorial planteado inicialmente desde el punto de vista teórico. Conclusiones Consideramos que la versión breve del IFM puede ser utilizada con éxito tanto a nivel clínico como para la investigación y, en este sentido, se sugiere que se siga indagando en la estructura factorial de la escala.

Abstract Background Mindfulness is getting more and more attention from psychological intervention contexts, but also from educational and organizational settings. As a consequence, there also is a growing need for tools to measure mindfulness. Objective The aim of this work is to present the Spanish adaptation psychometric properties of the short version Freiburg Mindfulness Inventory (FMI), a test based on Buddhist tradition. Method A sample of 543 participants (161 males and 379 females) with age average of 35.27 ( SD = 13.66) and heterogeneous educational and occupational background was studied. Results The scale internal consistency ( α = .86, ω = .87) as well as construct validity evidences can be considered appropriated. Exploratory factorial analyses suggest the FMI items are clustered in two related factors, unconditional acceptance, and full attention, as opposed to the initially proposed unifactorial model. Conclusions the FMI short version can be successfully used for clinical and research purposes although its factorial structure should be additionally tested.

Supervivencia en las personas que viven con VIH en el marco del sistema de salud colombiano 2011-2018 / Survival in people living with HIV in the framework the Colombian health system: 2011-2018

Resumen Objetivo: Describir la supervivencia a siete años y los principales factores asociados a esta, en las personas con VIH que fueron atendidas en el sistema de salud colombiano entre 2011 a 2018. Métodos: Análisis de supervivencia de una cohorte de 64 039 personas diagnosticadas con VIH en Colombia. Se aplicó el método de Kaplan-Meier para estimar la probabilidad de supervivencia a partir de la fecha del diagnóstico. Se ajustó un modelo de supervivencia paramétrico flexible de Royston Parmar. Resultados: La estimación de la supervivencia global a 7 años fue de 94,8% (IC 95%: 94,5-95,2). El mayor riesgo de muerte se presentó en los hombres (HR: 1,2; IC 95%: 1,1-1,4; p: 0,010); en personas ≥50 años de edad (HR: 3,1; IC 95%: 1,6-6,3; p: 0,002); en el régimen subsidiado (HR: 2,2; IC 95%: 1,9-2,5; p: <0,001); en la etapa sida (HR: 2,8; IC 95%: 2,1-3,7; p: <0,001); en quienes presentaron la última carga viral detectable (HR: 7,1; IC 95%: 6,0-8,3; p: <0,001); y en quienes mostraron conteo de linfocitos T CD4+ <350 células/μL (HR: 1,9; IC 95%: 1,4-2,4; p: <0,001). Conclusión: La probabilidad de la supervivencia de las personas que viven con VIH aumenta al ser diagnosticados en edades jóvenes, en quienes presenten un recuento de linfocitos T CD4+ ≥350 células/μL, una carga viral indetectable (< 50 copias/mL) y no se encuentren en etapa sida.

Summary Objective: to describe the seven-year survival and predictors of mortality among people with HIV who were treated in the Colombian health system between 2011 and 2018. Methods: 64 039 people diagnosed with HIV in Colombia were included. Kaplan-Meier analysis estimated the probability of survival from the date of diagnosis. A Royston Parmar flexible parametric survival model was fitted. Results: The overall survival at 7 years was 94.8% (95% CI: 94.5-95.2). Survival was related to sex (men, HR: 1.2; 95% CI: 1.1-1.4; p: 0.010); people ≥50 years of age (HR: 3.1; 95% CI: 1.6-6.3; p: 0.002); subsidized regime (HR: 2.2; 95% CI: 1.9-2.5; p: <0.001); AIDS stage (HR: 2.8; 95% CI: 2.1-3.7; p: <0.001); a detectable viral load (HR: 7.1; 95% CI: 6.0-8.3; p: <0.001); and a CD4+ Lymphocyte count <350 cells/μL (HR: 1.9; 95% CI: 1.4-2.4; p: <0.001). Conclusion: The probability of survival of people living with HIV increases when they are diagnosed at a young age, in those with a CD4+ T Lymphocyte count ≥350 cells/μL, an undetectable viral load (<50 copies/mL) and are not in the AIDS stage.

National Cancer Information System Within the Framework of Health Insurance in Colombia: A Real-World Data Approach to Evaluate Access to Cancer Care.

PURPOSE: The National Cancer Information System (NCIS) has been operating since 2014, including information reported by health care insurers and providers on people with cancer diagnosed and treated within the Colombian health system. Its main purpose is to identify barriers to an effective access to cancer diagnosis and treatment across the country. We aimed to describe the methodology, scope and results in terms of access to health services with real-world data provided by the NCIS. METHODS: Reporting of all cases of cancer by insurers and providers is mandatory by law. Data gathered include demographic and clinical information about new and old cases of cancer who receive health services. Over the years, the reporting process has been automated and it is currently performed in real time. Data quality is ensured through a standardized data-monitoring process. Access to health services is monitored by quality measures defined by consensus. RESULTS: Since 2015, prevalent cases of invasive cancer have increased from 163,776 to 331,021 in 2020 (increment of 102.12%). Regarding quality measures, the proportion of people staged at diagnosis has increased over the years, especially in breast cancer. Meanwhile, early diagnosis is still concerning for breast and prostate cancer. Time to diagnosis and treatment have not consistently reached the expected goals in breast, cervical, and prostate cancer, whereas they have shown a better level of compliance for stomach and colon and rectum tumors, still not reaching the highest performance. CONCLUSION: The real-world information approach provided by the NCIS may be complementary for cancer control planning in Colombia, emphasizing better management processes of health insurers and providers by identifying barriers for timely access to health care.

FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes.

FAM20C is a gene coding for a protein kinase that targets S-X-E/pS motifs on different phosphoproteins belonging to diverse tissues. Pathogenic variants of FAM20C are responsible for Raine syndrome (RS), initially described as a lethal and congenital osteosclerotic dysplasia characterized by generalized atherosclerosis with periosteal bone formation, characteristic facial dysmorphisms and intracerebral calcifications. The aim of this review is to give an overview of targets and variants of FAM20C as well as RS aspects. We performed a wide phenotypic review focusing on clinical aspects and differences between all lethal (LRS) and non-lethal (NLRS) reported cases, besides the FAM20C pathogenic variant description for each. As new targets of FAM20C kinase have been identified, we reviewed FAM20C targets and their functions in bone and other tissues, with emphasis on novel targets not previously considered. We found the classic lethal and milder non-lethal phenotypes. The milder phenotype is defined by a large spectrum ranging from osteonecrosis to osteosclerosis with additional congenital defects or intellectual disability in some cases. We discuss our current understanding of FAM20C deficiency, its mechanism in RS through classic FAM20C targets in bone tissue and its potential biological relevance through novel targets in non-bone tissues.

Adenocarcinoma indiferenciado como factor predictor de metástasis ganglionares en cáncer gástrico / Undifferentiated adenocarcinoma as a predictor of lymph nodemetastases in gastric cancer

Introducción. El grado de diferenciación celular en el estudio histopatológico del adenocarcinoma gástrico está descrito como un factor pronóstico determinante en el comportamiento clínico del tumor. El adenocarcinoma gástrico indiferenciado es considerado una variante agresiva de mal pronóstico, que se correlaciona con una alta tasa de metástasis ganglionares. Métodos. Estudio prospectivo descriptivo de una serie de casos en el cual se analizan los pacientes con adenocarcinoma gástrico indiferenciado, que fueron llevados a cirugía radical con gastrectomía y linfadenectomía DII y su correlación con la presencia de metástasis ganglionares en un período de dos años. Resultados. De enero de 2018 a enero de 2020 se recolectaron en la base de datos 113 pacientes con adenocarcinoma gástrico a quienes se les practicó gastrectomía total, disección ganglionar DII y reconstrucción esofagoyeyunal termino lateral con técnica de Orr más Y de Roux. Fueron clasificados histológicamente como adenocarcinoma gástrico indiferenciado 41 pacientes (36,3 %). La edad promedio de este grupo fue de 56 años con un rango entre 28-92 años. De ellos 30 fueron hombres (73 %) y 11 mujeres (27 %). El número promedio de ganglios linfáticos analizados por espécimen fue de 24. De los 41 pacientes con adenocarcinoma gástrico indiferenciado, 35 (85 %) tuvieron metástasis ganglionares, con 382 ganglios positivos en total, con un rango entre 1-38 y un promedio de 11 ganglios linfáticos positivos por espécimen. Discusión. En esta serie el adenocarcinoma gástrico indiferenciado se presentó en el 36,3 % de los casos y se correlacionó con un 85 % de presencia de metástasis ganglionares en estadios T3-T4

Introduction. The degree of cellular differentiation in the histopathological study of gastric adenocarcinoma is described as a determining prognostic factor in the clinical behavior of the tumor. Undifferentiated gastric adenocarcinoma is considered an aggressive variant with a poor prognosis, which is correlated with a high rate of lymph node metastasis.Methods. Descriptive prospective study of a series of cases in which patients with undifferentiated gastric adenocarcinoma who underwent radical surgery with DII gastrectomy and lymphadenectomy and their correlation with the presence of lymph node metastases in a period of two years. Results. From January 2018 to January 2020, 113 patients with gastric adenocarcinoma were collected in the database who underwent total gastrectomy, DII lymph node dissection and end-to-side esophagojejunal reconstruction with the Orr plus Roux-en-Y technique. Forty-one patients (36.3%) were histologically classified as undifferentiated gastric adenocarcinoma. The average age of this group was 56 years with a range between 28-92 years. Of these, 30 were men (73%) and 11 women (27%). The mean number of lymph nodes analyzed per specimen was 24. Of the 41 patients with undifferentiated gastric adenocarcinoma, 35 (85%) had lymph node metastases, with 382 positive nodes in total, with a range between 1-38 and a mean of 11 positive lymph nodes per specimen. Discussion. In this series, undifferentiated gastric adenocarcinoma occurred in 36.3% of cases and was correlated with 85% of the presence of lymph node metastases in T3-T4