Variables asociadas al deterioro cognitivo en pacientes de cáncer de colon

Objetivo: Identificar las variables predictoras de menor rendimiento cognitivo en pacientes de cáncer de colon tratados con cirugía que esperan recibir quimioterapia. Método: En una muestra de 89 pacientes de cáncer de colon se valoró la relación entre su rendimiento en tres dominios cognitivos (función ejecutiva, memoria verbal y habilidad psicomotora) y las siguientes variables: edad, sexo, años de escolaridad, estadio, pronóstico médico, comorbilidad, hemoglobina, ansiedad, depresión, astenia, calidad de vida, problemas físicos y psicosociales. Resultados: En la muestra predominan los varones (61,8%), mayores de 65 años (media 66,9), sin antecedentes neuropsicológicos (89,9%). Los datos correlacionales ponen de manifiesto relaciones selectivas entre alguna prueba de rendimiento cognitivo y ciertas variables evaluadas. Se destaca la existencia de correlaciones negativas de la edad, los problemas respiratorios y la percepción social de la calidad de vida con el rendimiento cognitivo en pruebas de memoria verbal, función ejecutiva y habilidad psicomotora (p < 0,05). Así mismo, los pacientes en estadio III del cáncer de colon rinden peor que aquellos con la enfermedad en estadio II y quienes tienen menos de cinco años de estudios difieren de los de más estudios en los tres dominios cognitivos (p < 0,05) Conclusiones: el perfil detectado de los enfermos de cáncer de colon de alto riesgo de déficit cognitivo es: paciente mayor, con enfermedad en estadio III, de escasa formación escolar, que tiene problemas respiratorios y una buena percepción de su calidad de vida social.Objective: Identify predictors of lower cognitive performance in colon cancer patients treated with surgery before undergoing chemotherapy. Methods: In a sample of 89 colon cancer patients, we evaluated the relation between their cognitive performance in three cognitive domains (executive function, verbal memory and psychomotor skill) and the following variables: Age, sex, years of study, stage, medical prognosis, comorbidity, haemoglobin, anxiety, depression, fatigue, quality of life, physical and psychosocial problems. Results: They are a predominantly male sample (61.8%), over 65 years (mean 66.9) without neuropsychological illness history (89.9%). But, data show correlational relationships between some cognitive performance test and certain variables assessed. There are remarkable negative correlations with age, respiratory problems and social perception of the quality of life, with lower cognitive performance on tests of verbal memory, executive function and psychomotor ability (p <0.05). Also, patients with stage III colon cancer performed worse than those with stage II disease and those with less than five years of study differ from most studies in the three cognitive domains (p < 0.05). Conclusions: The profile of patients with colon cancer at high risk of cognitive deficit is: Old age, with stage III disease, little formal education, breathing problems and a good perception of their quality of social lif

Families’ degree of satisfaction with pediatric telehomecare: interventional prospective pilot study in Catalonia

Home health monitoring; Pediatrics; Telehomecare; Videoconferencing; Satisfaction with care; Remote sensing technology; TelehealthVigilància de la salut domiciliària; Pediatria; Teleassistència domiciliària; Videoconferència; Satisfacció amb la cura; Tecnologia de teledetecció; TelesalutVigilancia de la salud en el hogar; Pediatría; Teleasistencia domiciliaria; Videoconferencia; Satisfacción con la atención; Tecnología de teledetección; TelesaludBackground: Pediatric home hospitalization improves the quality of life of children and their families, involving them in their children's care, while favoring the work-life balance of the family. In this context, technology guarantees accessibility to assistance, which provides security to users. From the perspective of the health care system, this could lower the demand for hospital services and reduce hospitalization costs. Objective: This study aimed to assess families' degree of satisfaction and acceptability of pediatric telehomecare and explore the clinical characteristics of children benefiting from the program. Methods: A total of 95 children and their families participated in the home-hospitalization pilot program operated by Sant Joan de Déu Hospital in Barcelona, Spain. Families were visited once a day and patients were monitored using a kit consisting of a scale, a thermometer, a pulse oximeter, and a blood pressure monitor. Data on parental experience, satisfaction, safety, and preference for care was collected by means of a questionnaire. Data about the children's characteristics were collected from medical records. Descriptive and comparative statistics were used to analyze the data. Results: A total of 65 survey respondents expressed very high levels of satisfaction. Families reported their experiences as being very positive, preferring home hospitalization in 94% (61/65) of cases, and gave high scores regarding the use of telemonitoring devices. The program did not record any readmissions after 72 hours and reported a very low number of adverse incidents. The user profile was very heterogeneous, highlighting a large number of respiratory patients and patients with infections that required endovenous antibiotic therapy. Conclusions: Pediatric home hospitalization through telemonitoring is a feasible and desirable alternative to traditional hospitalization, both from the perspective of families and the hospital. The results of this analysis showed a very high degree of satisfaction with the care received and that the home-based telemonitoring system resulted in few adverse incidents.This study was conducted with the support of the Secretary of Universities and Research of the Department of Business and Knowledge of the Generalitat de Catalunya

High p27 protein levels in chronic lymphocytic leukemia are associated to low Myc and Skp2 expression, confer resistance to apoptosis and antagonize Myc effects on cell cycle

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.Myc (c-Myc) counteracts p27 effects, and low p27 usually correlates with high Myc expression in human cancer. However there is no information on the co-expression of both genes in chronic lymphocytic leukemia (CLL). We found a lack of correlation between RNA and protein levels of p27 and Myc in CLL cells, so we determined the protein levels by immunoblot in 107 cases of CLL. We observed a high p27 protein expression in CLL compared to normal B cells. Ectopic p27 expression in a CLL-derived cell line resulted in cell death resistance. Surprisingly, Myc expression was very low or undetectable in most CLL cases analyzed, with a clear correlation between high p27 and low Myc protein levels. This was associated with low Skp2 expression, which is consistent with the Skp2 role in p27 degradation and with SKP2 being a Myc target gene. High Myc expression did not correlate with leukemia progression, despite that cell cycle-related Myc target genes were upregulated. However, biochemical analysis showed that the high p27 levels inhibited cyclin-Cdk complexes even in Myc expressing CLL cells. Our data suggest that the combination of high p27 and low Myc is a marker of CLL cells which is mediated by Skp2.The work has been funded by grants SAF11-23796 from MINECO and RD12/0036/0033 (to JL), and RD12/0036/0004 (to DC) and RD12/0036/0060 (to MAP) from Instituto Carlos III. These funding was co-sponsored by the European Union FEDER program. JC was recipient of a Fellowship from Fundación Marqués de Valdecilla and from the University of Cantabria.Peer Reviewe

Aortic remodelling induced by obstructive apneas is normalized with mesenchymal stem cells infusion

Obstructive sleep apnea syndrome (OSA) promotes aortic dilatation, increased stiffness and accelerated atherosclerosis, but the mechanisms of vascular remodelling are not known. We aimed to assess vascular remodelling, its mechanisms, and the effect of mesenchymal stem cells (MSC) infusions in a clinically relevant rat model of chronic OSA involving recurrent airway obstructions leading thoracic pressure swings and intermittent hypoxia/hypercapnia (OSA-rats). Another group of rats were placed in the same setup without air obstructions (Sham-rats) and were considered controls. Our study demonstrates that chronic, non-invasive repetitive airway obstructions mimicking OSA promote remarkable structural changes of the descending thoracic aorta such as eccentric aortic hypertrophy due to an increased wall thickness and lumen diameter, an increase in the number of elastin fibers which, in contrast, get ruptured, but no changes in tunica media fibrosis. As putative molecular mechanisms of the OSA-induced vascular changes we identified an increase in reactive oxygen species and renin-angiotensin system markers and an imbalance in oxide nitric synthesis. Our results also indicate that MSC infusion blunts the OSA-related vascular changes, most probably due to their anti-inflammatory properties

Development and validation of a sample entropy-based method to identify complex patient-ventilator interactions during mechanical ventilation

Patient-ventilator asynchronies can be detected by close monitoring of ventilator screens by clinicians or through automated algorithms. However, detecting complex patient-ventilator interactions (CP-VI), consisting of changes in the respiratory rate and/or clusters of asynchronies, is a challenge. Sample Entropy (SE) of airway flow (SE-Flow) and airway pressure (SE-Paw) waveforms obtained from 27 critically ill patients was used to develop and validate an automated algorithm for detecting CP-VI. The algorithm’s performance was compared versus the gold standard (the ventilator’s waveform recordings for CP-VI were scored visually by three experts; Fleiss’ kappa = 0.90 (0.87–0.93)). A repeated holdout cross-validation procedure using the Matthews correlation coefficient (MCC) as a measure of effectiveness was used for optimization of different combinations of SE settings (embedding dimension, m, and tolerance value, r), derived SE features (mean and maximum values), and the thresholds of change (Th) from patient’s own baseline SE value. The most accurate results were obtained using the maximum values of SE-Flow (m = 2, r = 0.2, Th = 25%) and SE-Paw (m = 4, r = 0.2, Th = 30%) which report MCCs of 0.85 (0.78–0.86) and 0.78 (0.78–0.85), and accuracies of 0.93 (0.89–0.93) and 0.89 (0.89–0.93), respectively. This approach promises an improvement in the accurate detection of CP-VI, and future study of their clinical implications.This work was funded by projects PI16/01606, integrated in the Plan Nacional de R+D+I and co-funded by the ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). RTC-2017-6193-1 (AEI/FEDER UE). CIBER Enfermedades Respiratorias, and Fundació Parc Taulí

COVID-19 mRNA Based Vaccine Immune-Response Assessment in Nursing Home Residents for Public Health Decision

Nursing home residents (NHR) have been targeted as a vaccination priority due to their higher risk of worse outcome after COVID-19 infection. The mRNA-based vaccine BTN2b2 was first approved in Europe for NHRs. The assessment of the specific vaccine immune response (both humoral and cellular) at long term in NHRs has not been addressed yet. A representative sample of 624 NHR subjects in Northern region of Spain was studied to assess immune response against full vaccination with BTN2b2. The anti-S1 antibody levels and specific T cells were measured at two and six months after vaccination. 24.4% of NHR had a previous infection prior to vaccination. The remaining NHR were included in the full vaccination assessment group (FVA). After two months, a 94.9% of the FVA presented anti-S1 antibodies, whereas those seronegative without specific cellular response were 2.54%. At long-term, the frequency of NHR within the FVA group with anti-S1 antibodies at six months were 88.12% and the seronegative subjects without specific cellular response was 8.07%. The cellular immune assays complement the humoral test in the immune vaccine response assessment. Therefore, the cellular immune assessment in NHRs allows for the fine tuning of those seronegative subjects with potential competent immune responses against the vaccine

Utility of CYP2D6 copy number variants as prognostic biomarker in localized anal squamous cell carcinoma

Background: Anal squamous cell carcinoma (ASCC) is an infrequent tumor whose treatment has not changed since the 1970s. The aim of this study is the identification of biomarkers allowing personalized treatments and improvement of therapeutic outcomes. Methods: Forty-six paraffin tumor samples from ASCC patients were analyzed by whole-exome sequencing. Copy number variants (CNVs) were identified and their relation to disease-free survival (DFS) was studied and validated in an independent retrospective cohort of 101 ASCC patients from the Multidisciplinary Spanish Digestive Cancer Group (GEMCAD). GEMCAD cohort proteomics allowed assessing the biological features of these tumors. Results: On the discovery cohort, the median age was 61 years old, 50% were males, stages I/II/III: 3 (7%)/16 (35%)/27 (58%), respectively, median DFS was 33 months, and overall survival was 45 months. Twenty-nine genes whose duplication was related to DFS were identified. The most representative was duplications of the CYP2D locus, including CYP2D6, CYP2D7P, and CYP2D8P genes. Patients with CYP2D6 CNV had worse DFS at 5 years than those with two CYP2D6 copies (21% vs. 84%; p <.0002, hazard ratio [HR], 5.8; 95% confidence interval [CI], 2.7–24.9). In the GEMCAD validation cohort, patients with CYP2D6 CNV also had worse DFS at 5 years (56% vs. 87%; p =.02, HR = 3.6; 95% CI, 1.1–5.7). Mitochondria and mitochondrial cell-cycle proteins were overexpressed in patients with CYP2D6 CNV. Conclusions: Tumor CYP2D6 CNV identified patients with a significantly worse DFS at 5 years among localized ASCC patients treated with 5-fluorouracil, mitomycin C, and radiotherapy. Proteomics pointed out mitochondria and mitochondrial cell-cycle genes as possible therapeutic targets for these high-risk patients. Plain Language Summary: Anal squamous cell carcinoma is an infrequent tumor whose treatment has not been changed since the 1970s. However, disease-free survival in late staged tumors is between 40% and 70%. The presence of an alteration in the number of copies of CYP2D6 gene is a biomarker of worse disease-free survival. The analysis of the proteins in these high-risk patients pointed out mitochondria and mitochondrial cell-cycle genes as possible therapeutic targets. Therefore, the determination of the number of copies of CYP2D6 allows the identification of anal squamous carcinoma patients with a high-risk of relapse that could be redirected to a clinical trial. Additionally, this study may be useful to suggest new treatment strategies to increase current therapy efficacyIdiPAZ, Grant/Award Number: Jesús Antolín Garciarena Fellowship; European Proteomics Infrastructure Consortium, Grant/Award Number: 823839, Horizon 2020 Programm

Changes in heart rate variability of flight phobics during a paced breathing task and exposure to fearful stimuli

The aim of this experiment was to explore changes in the vagally mediated heart rate variability (HRV) of flight phobics during exposure to feared stimuli. A paced breathing task was included to control for respiration effects. Sixty-one flight phobics (40 women) with a mean age of 39.07 years (SD = 11.24) participated in the study. The root mean of the squared successive interbeat intervals differences (RMSSD) was taken as the time domain measure of HRV. High frequency (HF: 0.15-0.4 Hz) and low frequency (LF: 0.04-0.15 Hz) band power was calculated on the ECG recordings obtained during free breathing baseline (BL), paced breathing (PB), and exposure (E) to fearful stimuli. Heart rate unexpectedly increased from BL to PB, and decreased from PB to E, while no differences were found between BL and E. No changes in the RMSSD were seen across conditions. HF band power increased, as expected, from BL to PB, and a significant decrease was found from PB to E. LF band power, as well as the LF/HF ratio, increased from BL to E. Discussion focuses on (a) the role of the parasympathetic and the sympathetic nervous systems in fear-related situations, and (b) the effects of paced breathing in preparing the system to cope with threatEn este estudio se analizan los cambios en la variabilidad de la tasa cardíaca (HRV) relacionada con el sistema vagal en sujetos fóbicos durante la exposición a estímulos temidos. Se ha introducido una tarea de respiración pautada para controlar los efectos de la misma en la medida de la HRV. Han participado en el estudio 61 pacientes con fobia a volar (40 mujeres) con una edad media de 39,07 años (SD =11,24). Como medida de la HRV en el dominio del tiempo se ha tomado la RMSSD (media cuadrática de las diferencias de los intervalos RR sucesivos). Se ha calculado la potencia espectral en las bandas de alta (HF: 0.15-0.4 Hz) y de baja frecuencia (LF: 0.04-0.15 Hz) sobre los registros de ECG obtenidos durante una línea base sin respiración controlada (BL), una fase de respiración pautada (PB) y la exposición (E) a estímulos temidos. La tasa cardíaca aumentó de forma inesperada de BL a PB, disminuyó de PB a E, y no se obtuvieron diferencias entre BL y E. No se observaron cambios en RMSSD entre las tres condiciones. La potencia espectral de HF aumentó, como se esperaba, de BL a PB, y disminuyó de forma significativa de PB a E. La potencia espectral de LF, así como la relación LF/HF, aumentó de BL a E. La discusión se centra en (a) el papel de los sistemas simpático y parasimpático en las situaciones de miedo, y (b) los efectos de la respiración pautada en la preparación del sistema para afrontar estímulos temido

Stratifying diffuse large B-cell lymphoma patients treated with chemoimmunotherapy: GCB/non-GCB by immunohistochemistry is still a robust and feasible marker

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas that can be classified into three molecular subtypes by gene expression profiling (GEP): GCB, ABC and unclassified. Immunohistochemistry-based cell of origin (COO) classification, as a surrogate for GEP, using three available immunohistochemical algorithms was evaluated in TMA-arranged tissue samples from 297 patients with de novo DLBCL treated by chemoimmunotherapy (R-CHOP and R-CHOP-like regimens). Additionally, the prognostic impacts of MYC, BCL2, IRF4 and BCL6 abnormalities detected by FISH, the relationship between the immunohistochemical COO classification and the immunohistochemical expression of MYC, BCL2 and pSTAT3 proteins and clinical data were evaluated. In our series, non-GCB DLBCL patients had significantly worse progression-free survival (PFS) and overall survival (OS), as calculated using the Choi, Visco-Young and Hans algorithms, indicating that any of these algorithms would be appropriate for identifying patients who require alternative therapies to R-CHOP. Whilst MYC abnormalities had no impact on clinical outcome in the non-GCB subtype, those patients with isolated MYC rearrangements and a GCB-DLBCL phenotype had worse PFS and therefore might benefit from novel treatment approaches