Family burden after critical illness: the forgotten caregivers / La sobrecarga familiar tras una enfermedad crítica: los cuidadores olvidados

Objective To determine the incidence of primary caregiver burden in a cohort of family members of critically ill patients admitted to ICU and to identify risk factors related to its development in both the patient and the family member. Design Prospective observational cohort study was conducted for 24 months. Setting Hospital Universitario Clínico San Cecilio, Granada. Patients The sample was the primary caregivers of all patients with risk factors for development of PICS (Post-Intensive Care Syndrome). Interventions The follow-up protocol consisted of evaluation 3 months after discharge from the ICU in a specific consultation. Main variables of interest The scales used in patients were Barthel, SF-12, HADS, Pfeiffer, IES-6 and in relatives the Apgar and Zarit. Results A total of 93 patients and caregivers were included in the follow-up. 15 relatives did not complete the follow-up questionnaires and were excluded from the study. The incidence of PICS-F (Family Post Intensive Care Syndrome) defined by the presence of primary caregiver burden in our cohort of patients is 34.6% (n=27), 95% CI 25.0−45.7. The risk factors for the development of caregiver burden are the presence of physical impairment, anxiety or post-traumatic stress in the patient, with no relationship found with the characteristics studied in the family member. Conclusions One out of 3 relatives of patients with risk factors for the development of PICS presents at 3 months caregiver burden. This is related to factors dependent on the patient's state of health. (AU)

Objetivo Determinar la incidencia de la sobrecarga del cuidador principal en una cohorte de familiares de pacientes críticos ingresados en UCI e identificar los factores de riesgo relacionados con su desarrollo tanto en el paciente como en el familiar. Diseño Estudio de cohortes observacional prospectivo durante 24 meses. Ámbito Hospital Universitario Clínico San Cecilio de Granada. Pacientes La muestra estuvo compuesta por los cuidadores principales de todos los pacientes con factores de riesgo para el desarrollo de SPCI (Síndrome Post-Cuidados Intensivos). Intervenciones El protocolo de seguimiento consistió en la evaluación a los 3 meses del alta de la UCI en una consulta específica. Variables de interés principales Las escalas utilizadas fueron Barthel, SF-12, HADS, Pfeiffer, IES-6, Apgar y Zarit. Resultados Un total de 93 pacientes y cuidadores fueron incluidos en el seguimiento. 15 cuidadores no completaron los cuestionarios de seguimiento y fueron excluidos del estudio. La incidencia de PICS-F (Síndrome Post-Cuidados Intensivos Familiar) definido por la presencia de sobrecarga del cuidador en nuestra cohorte es del 34,6% (n=27), IC 95% 25,0–45,7. Los factores de riesgo para el desarrollo del mismo son la presencia de deterioro físico, ansiedad o estrés postraumático en el paciente, no encontrándose relación con las características estudiadas en el familiar. Conclusiones Uno de cada 3 familiares de pacientes con factores de riesgo para el desarrollo de SPCI presenta a los 3 meses sobrecarga del cuidador, relacionándose con factores dependientes del estado de salud del paciente. (AU)

Family burden after critical illness: the forgotten caregivers.

OBJECTIVE: To determine the incidence of primary caregiver burden in a cohort of family members of critically ill patients admitted to ICU and to identify risk factors related to its development in both the patient and the family member. DESIGN: Prospective observational cohort study was conducted for 24 months. SETTING: Hospital Universitario Clínico San Cecilio, Granada. PATIENTS: The sample was the primary caregivers of all patients with risk factors for development of PICS (Post-Intensive Care Syndrome). INTERVENTIONS: The follow-up protocol consisted of evaluation 3 months after discharge from the ICU in a specific consultation. MAIN VARIABLES OF INTEREST: The scales used in patients were Barthel, SF-12, HADS, Pfeiffer, IES-6 and in relatives the Apgar and Zarit. RESULTS: A total of 93 patients and caregivers were included in the follow-up. 15 relatives did not complete the follow-up questionnaires and were excluded from the study. The incidence of PICS-F (Family Post Intensive Care Syndrome) defined by the presence of primary caregiver burden in our cohort of patients is 34.6% (n=27), 95% CI 25.0-45.7. The risk factors for the development of caregiver burden are the presence of physical impairment, anxiety or post-traumatic stress in the patient, with no relationship found with the characteristics studied in the family member. CONCLUSIONS: One out of 3 relatives of patients with risk factors for the development of PICS presents at 3 months caregiver burden. This is related to factors dependent on the patient's state of health.

Computational pathology in 2030: a Delphi study forecasting the role of AI in pathology within the next decade.

BACKGROUND: Artificial intelligence (AI) is rapidly fuelling a fundamental transformation in the practice of pathology. However, clinical integration remains challenging, with no AI algorithms to date in routine adoption within typical anatomic pathology (AP) laboratories. This survey gathered current expert perspectives and expectations regarding the role of AI in AP from those with first-hand computational pathology and AI experience. METHODS: Perspectives were solicited using the Delphi method from 24 subject matter experts between December 2020 and February 2021 regarding the anticipated role of AI in pathology by the year 2030. The study consisted of three consecutive rounds: 1) an open-ended, free response questionnaire generating a list of survey items; 2) a Likert-scale survey scored by experts and analysed for consensus; and 3) a repeat survey of items not reaching consensus to obtain further expert consensus. FINDINGS: Consensus opinions were reached on 141 of 180 survey items (78.3%). Experts agreed that AI would be routinely and impactfully used within AP laboratory and pathologist clinical workflows by 2030. High consensus was reached on 100 items across nine categories encompassing the impact of AI on (1) pathology key performance indicators (KPIs) and (2) the pathology workforce and specific tasks performed by (3) pathologists and (4) AP lab technicians, as well as (5) specific AI applications and their likelihood of routine use by 2030, (6) AI's role in integrated diagnostics, (7) pathology tasks likely to be fully automated using AI, and (8) regulatory/legal and (9) ethical aspects of AI integration in pathology. INTERPRETATION: This systematic consensus study details the expected short-to-mid-term impact of AI on pathology practice. These findings provide timely and relevant information regarding future care delivery in pathology and raise key practical, ethical, and legal challenges that must be addressed prior to AI's successful clinical implementation. FUNDING: No specific funding was provided for this study.

Generation of a H9 Clonal Cell Line With Inducible Expression of NUP98-KDM5A Fusion Gene in the AAVS1 Safe Harbor Locus.

Pediatric acute myeloid leukemia (AML) is a rare and heterogeneous disease that remains the major cause of mortality in children with leukemia. To improve the outcome of pediatric AML we need to gain knowledge on the biological bases of this disease. NUP98-KDM5A (NK5A) fusion protein is present in a particular subgroup of young pediatric patients with poor outcome. We report the generation and characterization of human Embryonic Stem Cell (hESC) clonal lines with inducible expression of NK5A. Temporal control of NK5A expression during hematopoietic differentiation from hESC will be critical for elucidating its participation during the leukemogenic process.

Agreement of blood glucose measured with glucose meter in arterial, central venous, and capillary samples in adult critically ill patients.

BACKGROUND: The measurement of blood glucose in critically ill patients is still performed in many ICUs with glucose meters and capillary samples. Several prevalent factors in these patients affect the accuracy of the results and should be interpreted with caution. A weak recommendation from the Surviving Sepsis Campaign (SSC) suggests the use of arterial blood rather than capillary blood for point of care testing using glucose meters. AIMS AND OBJECTIVES: To analyse the agreement between arterial, central venous, and capillary blood samples of glucose values measured by glucose meter in critically ill patients and study potential confounding factors. DESIGN: Prospective cross-sectional study in a general intensive care unit (ICU). Patients needing insulin treatment (subcutaneous or intravenous) and blood glucose control were included. METHODS: Standardized collection of blood samples and measurement of glucose values with a glucometer. Agreement was studied by the Bland-Altman method and stratified analysis of disagreement-survival plots was used to study the influence of haematocrit, pH range, SOFA score, capillary refilling time, intravenous insulin infusion, and lactic acid. RESULTS: A total of 297 measurements from 54 patients were included. The mean arterial blood glucose was 150.42 (range 31-345 mg/dL). In the graphical analysis, there is a poor agreement both in capillary and venous central to arterial samples, but in opposite direction (underestimation of capillary and overestimation of central venous). Factors associated with a reduction in the agreement between arterial and capillary samples were elevated lactate, poor capillary refilling, and hemodynamic failure. Patients without hemodynamic compromise have an acceptable agreement with values for absolute differences of 16 mg/dL for a disagreement of 10%. CONCLUSIONS: In critically ill patients, the measurement of blood glucose with a glucose meter should be performed with arterial samples whenever possible. Capillary samples do not accurately estimate arterial blood glucose values in patients with shock and/or vasoactive drugs and underestimate the values in the range of hypoglycemia. Venous samples are subject to error because of potential contamination. RELEVANCE TO CLINICAL PRACTICE: This study adds support to the recommendation of using arterial blood rather than capillary or venous blood when using glucose meters in critically ill patients, especially in those with hemodynamic failure.

Small cell lung cancer: Recent changes in clinical presentation and prognosis.

BACKGROUND: Small cell lung cancer (SCLC) is a leading cause of death all over the world. Diagnostic and therapeutic arsenals have improved in recent years, but we are unsure as to whether these advances have been transferred to clinical practice. The aim of this study was to evaluate differences in SCLC diagnostic processes and short-term survival rates between two recent cohorts. METHODS: A prospective, observational study was conducted with patients diagnosed with SCLC (either at extensive or limited stages) in the 2011-2016 period. Patients were divided into two cohorts (2011-2013 and 2014-2016) and followed up for 1 year after diagnosis. RESULTS: Around 713 patients with lung cancer were selected, 134 of whom had SCLC (74 patients in the 2011-2013 cohort and 60 in the 2014-2016 cohort). We observed a chronological increase in the use of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and positron emission tomography-computed tomography (PET-CT) between the cohorts. Overall, short-term survival was similar between the two groups and improved survival was associated with age and limited stage. CONCLUSIONS: Changes in diagnostic process in SCLC have been observed towards a more precise stadification. Although short-term survival has not changed for SCLC, it is unclear that the real benefit of PET-CT and EBUS-TBNA is far from correct disease staging.

Biological and prognostic differences between symptomatic colorectal carcinomas and those detected by screening.

INTRODUCTION: Few studies have been conducted to establish the relationship between colorectal cancer screening programmes and survival adjusting by stage and, to determine whether there are differences, at a biological level, between the tumours of asymptomatic and symptomatic patients. Accordingly, the aim of this study is to evaluate clinical, biological and survival differences between symptomatic colorectal tumours and those detected by screening. STUDY METHOD: A prospective cohort study was performed of patients subjected to surgical intervention during the period 2010-2012, at different hospitals in Spain. In every case, clinical, pathological, biological and survival-related variables were obtained. RESULTS: A total of 2634 patients from the CARESS-CCR cohort were analysed; of these, 220 were diagnosed through screening. The asymptomatic patients were younger, had a higher Body Mass Index (BMI), a lower degree of perineural invasion and a less advanced T stage and nodular stage, and the tumour was frequently located on the right side of the colon. All of these differences were statistically significant. The serum tumour marker carbohydrate antigen 19.9 (CA 19.9) was found more frequently in the symptomatic patients (p < 0.05). However, no significant differences were found regarding the markers of tumour biology: Ki67 (proliferation), CD105 (angiogenesis) and the Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay (apoptosis). The patients with asymptomatic tumours had a lower mortality at five years than those diagnosed presenting symptoms. CONCLUSIONS: The detection method employed influenced the survival of patients with colorectal cancer and there were no significant biological differences between the study groups.

Nefropatía familiar hiperuricemiante: nueva mutación familiar del gen de la uromodulina / Familial hyperuricaemic nephropathy: New mutation in uromodulin gen

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Clinical-pathological characteristics and short-term follow-up associated with proliferation, apoptosis and angiogenesis in a prospective cohort of patients with colorectal tumours.

We investigate the clinical and pathological features related to variations in colorectal tumour apoptosis, proliferation and angiogenesis and the influence of the latter in short-term mortality (2 years); 551 tumour samples from a prospective cohort of patients with colorectal cancer were examined and tumour biology markers were determined as follows: percentage of apoptotic cells, by the terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling technique; Ki-67 antigen, as a cell proliferation marker and density of microvessels (as a marker of angiogenesis). An increase in the percentage of cellular apoptosis is significantly related to the presence of poorly differentiated tumours, with vascular invasion (p < 0.001). The CD105 angiogenesis marker is not related to any clinical-pathological parameter except that of higher frequency in older patients (p = 0.03). Ki-67 is more frequently expressed in tumours with less nervous invasion (p = 0.05). Neither apoptosis nor angiogenesis present any significant association with short-term survival. The only marker clearly related to 2-year survival is Ki-67, which is shown to be a good prognostic factor in the multivariate analysis (hazard ratio = 0.49; 95% confidence interval = 0.27-0.90). Therefore, in a prospective cohort of colorectal cancer patients, only Ki-67 is a marker of good prognosis in short-term follow-up.

Definición clínico-patológica de los subtipos de epilepsia temporal medial con esclerosis del hipocampo / Clinical and pathological definition of temporal medium epilepsy subtypes with hypocampic sclerosis

Antecedentes y objetivo: La epilepsia temporal con esclerosis hipocampal es la causa más frecuente de epilepsia refractaria, y la indicación más común de cirugía. Aunque eficaz, la cirugía fracasa hasta en un 40% de los pacientes. El objetivo de nuestro trabajo es establecer una correlación entre los distintos subtipos histológicos de epilepsia temporal con esclerosis hipocampal y el pronóstico, control de crisis, efectos secundarios y retirada de fármacos anticomiciales en los pacientes con epilepsia resistente a fármacos intervenidos. Pacientes y método: Se analizaron de forma retrospectiva las historias clínicas y muestras anatomopatológicas de 228 pacientes con epilepsia temporal intervenidos en nuestro centro entre los años 1993 y 2014. Todos fueron sometidos a una evaluación prequirúrgica estándar e intervenidos mediante una resección temporal anterior (modificada de Spencer). El estudio anatomopatológico incluyó el protocolo de hematoxilina-eosina e inmunohistoquímico estándar, con especial interés en la valoración de pérdida neuronal con NeuN. El control de las crisis fue valorado de acuerdo a la escala de resultados de la ILAE y de Engel. El seguimiento medio fue de 8,6 años (2-19). Resultados: A los 10 años tras la intervención, un 67,9% de los pacientes se encontraban libres de crisis (ILAE 1). Un 77,5% de los pacientes estaba libre de crisis (Engel 1) al final del seguimiento. La probabilidad de quedar sin crisis (ILAE 1) tras la cirugía a los 2 (p = 0,042), 5 (p = 0,001) y 7 (p = 0,022) años fue mayor en las formas clásica y severa frente a las formas de esclerosis aislada CA1 y CA4. Una mayor pérdida neuronal medida con NeuN en CA1 se relacionó con un mejor resultado en el control de las crisis (análisis multivariante, p = 0,08). La presencia de antecedentes personales desencadenantes de epilepsia se relacionó con una mayor pérdida neuronal en CA1 (p = 0,028) y CA3 (p = 0,034), y la presencia de auras psíquicas con una mayor pérdida de neuronas en CA3 (p = 0,025). En nuestro caso, la probabilidad de dejar la medicación se relacionó con la presencia de antecedentes personales (p = 0,003) y, de forma inversa, con la pérdida neuronal en CA1 (p = 0,036) y CA3 (p = 0,038). El mayor deterioro de memoria verbal ocurrió en aquellos pacientes con menor pérdida neuronal en CA1 (p = 0,023), CA2 (p = 0,049) y CA3 (p = 0,035). Conclusiones: Los resultados señalan que los subtipos clásico y severo tienen un mejor pronóstico en el control de las crisis frente a las formas atípicas, validándose la utilidad clínica y pronóstica de la clasificación de consenso de los subtipos histológicos de esclerosis hipocampal de la ILAE. Se ha demostrado el valor de la inmunohistoquímica en la epilepsia temporal con esclerosis hipocampal como un elemento clave para determinar el pronóstico en el control de las crisis y neuropsicológico de los pacientes tras la cirugía

Background and objective: Mesial temporal lobe epilepsy with hippocampal sclerosis is the most common cause of refractory epilepsy, and the most common indication for surgery. Although effective, surgery fails in up to 40% of patients. The objective of our study was to establish a correlation between the different histological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis and the prognosis, seizures control, side effects and anticonvulsivant drug withdrawal in patients with refractory epilepsy. Patients and method: Clinical histories and anatomopathological specimens of 228 patients with temporal epilepsy surgically obtained at our hospital between 1993 and 2014 were retrospectively analysed. All patients underwent a standard preoperative evaluation and anterior temporal resection (modified from Spencer). The anatomopathological study included the standard hematoxylin-eosin and immunohistochemical protocol, with special interest in the assessment of neuronal loss with NeuN. Seizure control was assessed according to the scale of results of the ILAE and Engel. The mean follow-up was 8.6 years (2-19). Results: At 10 years after the intervention, 67.9% of patients were seizure-free (ILAE 1) and as many as 77.5% of the patients were seizure-free (Engel 1) at the end of the follow-up. The probability of not having a seizure (ILAE 1) after surgery at 2 (p=.042), 5 (p=.001) and 7 years (p=.22) was higher in classic and severe forms compared to isolated sclerosis CA1 and CA4 forms. Higher neuronal loss measured with the NeuN immunostain in CA1 was associated with better outcome in seizure management (multivariate analysis, p=.08). The presence of a personal history of epilepsy was associated with greater neuronal loss in CA1 (p=.028) and CA3 (p=.034), and the presence of psychic auras was related with greater neuronal loss in CA3 (p=.025). In our case, the probability of medication withdrawal was related to the presence of personal history (p=.003) and, inversely, to neuronal loss in CA1 (p=.036) and CA3 (p=.038). The greatest impairment of verbal memory occurred in those patients with a lower neuronal loss in CA1 (p=.023), CA2 (p=.049) and CA3 (p=.035). Conclusions: The results indicate that the classical and severe subtypes have a better prognosis in the control of seizures against the atypical forms, validating the clinical and prognostic utility of the classification of histological subtypes of hippocampal sclerosis from the ILAE. The value of the immunohistochemistry in the mesial temporal lobe epilepsy with hippocampal sclerosis has been demonstrated as a key element to determine the neuropsychological prognosis and seizure management of the patients after surgery

[Clinical and pathological definition of temporal medium epilepsy subtypes with hypocampic sclerosis]. / Definición clínico-patológica de los subtipos de epilepsia temporal medial con esclerosis del hipocampo.

BACKGROUND AND OBJECTIVE: Mesial temporal lobe epilepsy with hippocampal sclerosis is the most common cause of refractory epilepsy, and the most common indication for surgery. Although effective, surgery fails in up to 40% of patients. The objective of our study was to establish a correlation between the different histological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis and the prognosis, seizures control, side effects and anticonvulsivant drug withdrawal in patients with refractory epilepsy. PATIENTS AND METHOD: Clinical histories and anatomopathological specimens of 228 patients with temporal epilepsy surgically obtained at our hospital between 1993 and 2014 were retrospectively analysed. All patients underwent a standard preoperative evaluation and anterior temporal resection (modified from Spencer). The anatomopathological study included the standard hematoxylin-eosin and immunohistochemical protocol, with special interest in the assessment of neuronal loss with NeuN. Seizure control was assessed according to the scale of results of the ILAE and Engel. The mean follow-up was 8.6 years (2-19). RESULTS: At 10 years after the intervention, 67.9% of patients were seizure-free (ILAE 1) and as many as 77.5% of the patients were seizure-free (Engel 1) at the end of the follow-up. The probability of not having a seizure (ILAE 1) after surgery at 2 (p=.042), 5 (p=.001) and 7 years (p=.22) was higher in classic and severe forms compared to isolated sclerosis CA1 and CA4 forms. Higher neuronal loss measured with the NeuN immunostain in CA1 was associated with better outcome in seizure management (multivariate analysis, p=.08). The presence of a personal history of epilepsy was associated with greater neuronal loss in CA1 (p=.028) and CA3 (p=.034), and the presence of psychic auras was related with greater neuronal loss in CA3 (p=.025). In our case, the probability of medication withdrawal was related to the presence of personal history (p=.003) and, inversely, to neuronal loss in CA1 (p=.036) and CA3 (p=.038). The greatest impairment of verbal memory occurred in those patients with a lower neuronal loss in CA1 (p=.023), CA2 (p=.049) and CA3 (p=.035). CONCLUSIONS: The results indicate that the classical and severe subtypes have a better prognosis in the control of seizures against the atypical forms, validating the clinical and prognostic utility of the classification of histological subtypes of hippocampal sclerosis from the ILAE. The value of the immunohistochemistry in the mesial temporal lobe epilepsy with hippocampal sclerosis has been demonstrated as a key element to determine the neuropsychological prognosis and seizure management of the patients after surgery.

Pseudolinfoma de la mama: entidad inusual. Descripción de un caso y revisión de la literatura / Pseudolymphoma of the breast: an unusual entity. A case report and a review of the literature

El pseudolinfoma de la mama es una entidad considerada como un proceso patológico benigno cuya naturaleza puede ser un proceso reactivo; suele presentarse habitualmente como una tumoración de superficie irregular, con bordes definidos, indolora y de crecimiento lento. Morfológicamente se asemeja al linfoma, con el cual debe hacerse su principal diagnóstico diferencial, ya que el pronóstico y el tratamiento de estas 2 entidades varían considerablemente. Presentamos el caso de una mujer en la quinta década de la vida, con una lesión nodular en la mama derecha de 2 años de evolución, al momento del diagnóstico, sin evidencia de compromiso sistémico. Los hallazgos radiológicos orientaban hacia un proceso tumoral/inflamatorio, por lo que para su diagnóstico fue necesario un estudio anatomopatológico, inmunohistoquímico y molecular (AU)

Pseudolymphoma of the breast is considered a benign lesion, perhaps a reactive process, and usually presents as a slow growing, painless tumour with well-defined borders and an irregular surface. The morphological appearance resembles that of lymphoma and therefore a careful differential diagnosis should be made as the prognosis and treatment of these two entities vary considerably. We report the case of a woman in the fifth decade of life, who presented with a two year history of a nodular lesion in her right breast. There was no evidence of systemic disease. Radiological imagery suggested a tumour or inflammatory process and a biopsy was necessary for further histopathological, immunohistochemical and molecular studies (AU)

Aplasia medular en paciente con nefropatía lúpica terminal y c-ANCA (+) / Medullary aplasia in c-ANCA positive patient with end-stage lupus nephritis

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