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5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines, This project has been financed with SEOM and SEFF resources

Obesity is a preventable risk factor for cerebrovascular disorders and it is associated with cerebral grey and white matter changes. Specifically, individuals with obesity show diminished grey matter volume and thickness, which seems to be more prominent among fronto-temporal regions in the brain. At the same time, obesity is associated with lower microstructural white matter integrity, and it has been found to precede increases in white matter hyperintensity load. To date, however, it is unclear whether these findings can be attributed solely to obesity or whether they are a consequence of cardiometabolic complications that often co-exist with obesity, such as low-grade systemic inflammation, hypertension, insulin resistance, or dyslipidemia. In this narrative review we aim to provide a comprehensive overview of the potential impact of obesity and a number of its cardiometabolic consequences on brain integrity, both separately and in synergy with each other. We also identify current gaps in knowledge and outline recommendations for future research.

Additional file 2. Informed Consent v4.0 18th March 2021.

Additional file 1. RELEASE Protocol v5.0 14th May 2021.

OBJECTIVE: Life expectancy and obesity rates have drastically increased in recent years. An unhealthy weight is related to long-lasting medical disorders that might compromise the normal course of aging. The aim of the current study of brain connectivity patterns was to examine whether adults with obesity would show signs of premature aging, such as lower segregation, in large-scale networks. METHODS: Participants with obesity (n = 30, mean age = 32.8 ± 5.68 years) were compared with healthy-weight controls (n = 33, mean age = 30.9 ± 6.24 years) and senior participants who were stroke-free and without dementia (n = 30, mean age = 67.1 ± 6.65 years) using resting-state magnetic resonance imaging and graph theory metrics (i.e., small-world index, clustering coefficient, characteristic path length, and degree). RESULTS: Contrary to our hypothesis, participants with obesity exhibited a higher clustering coefficient compared with senior participants (t = 5.06, p < .001, d = 1.23, 95% CIbca = 0.64 to 1.88). Participants with obesity also showed lower global degree relative to seniors (t = -2.98, p = .014, d = -0.77, 95% CIbca = -1.26 to -0.26) and healthy-weight controls (t = -2.92, p = .019, d = -0.72, 95% CIbca = -1.19 to -0.25). Regional degree alterations in this group were present in several functional networks. CONCLUSIONS: Participants with obesity displayed greater network clustering than did seniors and also had lower degree compared with seniors and individuals with normal weight, which is not consistent with the notion that obesity is associated with premature aging of the brain. Although the cross-sectional nature of the study precludes causal inference, the overly clustered network patterns in obese participants could be relevant to age-related changes in brain function because regular networks might be less resilient and metabolically inefficient.

Additional file 3. Supplementary Tables 1 and 2.

Clinical trials show that nivolumab has remarkable activity against relapsed/refractory classical Hodgkin lymphoma (cHL). However, the role of allogeneic hematopoietic stem cell transplantation (alloHSCT) as consolidation therapy in these patients remains controversial. We performed a retrospective analysis of data from 74 patients treated with nivolumab. The overall response rate was 58% (30.6% complete responses). Treatment-related adverse events were reported in 56.8% of patients (grade =3 in 9.4%). The main reasons for nivolumab discontinuation were referral for transplantation (41.7% patients) and disease progression (37.5%). The 2 year overall survival (OS) rate was 52% for the whole series. Ultimately, 39 patients received alloHSCT. The cumulative incidence of grade II-IV acute graft-versus-host disease was 33.3% (grade III-IV in two patients). The cumulative incidence of non-relapse mortality was 13.2%. Among nivolumab responding patients, 2 year OS and progression free survival (PFS) were higher for patients who underwent consolidation with alloHSCT (77.5% vs. 42.6%, p=0.126; and 73.9% vs. 27.2%, p=0.025, respectively). Thus, efficacy and safety of nivolumab is comparable with that reported in previous clinical trials. The percentage of patients who bridged to transplantation was high, indicating a preference for Spanish physicians. These results suggest that consolidation alloHSCT increases OS and PFS.

Life expectancy and obesity rates have drastically increased in recent years. An unhealthy weight is related to long-lasting biological deregulations that might compromise the normal course of development and the so-called “successful aging”. The aim of the current study was to test whether an obesity status could mimic the functional organization of an otherwise healthy aged brain. To this end, we included adults with (N = 32, mean age 34.5 ± 6.49) and without obesity (N = 34, mean age 32.7 ± 6.79) as well as adolescents with obesity (N = 30, mean age 15.3 ± 2.64) and normal-weight (N = 31, mean age 15.6 ± 2.60). A sample of stroke-free non-obese and non-demented seniors was also entered (N = 32, mean age 66.1 ± 7.43). Participants underwent a resting-state MRI acquisition and graph-based measurements of segregation, integration and robustness (i.e., mean degree and strength) were calculated. Obesity in adults was accompanied by a broad pattern of losses in network robustness when compared to healthy-weight adults and seniors, as well as increases in network segregation relative to elders. Differences in adolescents followed the same direction yet did not survive multiple comparison adjustment. No interaction emerged when exploring the transition from childhood to adulthood accounting for body-weight status. While more research is needed, we offer preliminary evidence of an obesity status negatively rendering network resilience, which could compromise the normal course of aging.

Objective: Overweight (body mass index or BMI = 25 kg/m(2)) and stress interact with each other in complex ways. Overweight promotes chronic low-inflammation states, while stress is known to mediate caloric intake. Both conditions are linked to several avoidable health problems and to cognitive decline, brain atrophy, and dementia. Since it was proposed as a framework for the onset of mental illness, the allostatic load model has received increasing attention. Although changes in health and cognition related to overweight and stress are well-documented separately, the association between allostatic load and brain integrity has not been addressed in depth, especially among overweight subjects. Method: Thirty-four healthy overweight-to-obese and 29 lean adults underwent blood testing, neuropsychological examination, and magnetic resonance imaging to assess the relationship between cortical thickness and allostatic load, represented as an index of 15 biomarkers (this is, systolic and diastolic arterial tension, glycated hemoglobin, glucose, creatinine, total cholesterol, HDL and LDL cholesterol, triglycerides, c-reactive protein, interleukin-6, insulin, cortisol, fibrinogen, and leptin). Results: Allostatic load indexes showed widespread positive and negative significant correlations (p < 0.01) with cortical thickness values depending on body-weight status. Conclusion: The increase of allostatic load is linked to changes in the gray matter composition of regions monitoring behavior, sensory-reward processing, and general cognitive function.

El síndrome de apneas-hipoapneas del sueño, en lo adelante (SAHS) es una alteración que actualmente afecta a un número elevado de niños y adolescentes. Esta revisión tiene como objetivo evaluar los factores que generan esta alteración y el riesgo de padecer otro tipo de enfermedad asociada al SAHS. Los artículos seleccionados para ser incluidos en esta revisión se identificaron a través de GOOGLE SCHOLAR con un total de 50 artículos. La validez de los artículos estuvo dada por el grado de evidencias demostrado, por las recomendaciones que dejan y por la aplicabilidad a nuestro contexto. Esta revisión ha considerado los estudios que investigan el SAHS en niños y adolescentes. También se han tenido en cuenta los que relacionan esta alteración con la obesidad, la hipertensión arterial, la actividad física y otras variables. Los estudios demuestran que el SAHS está relacionado con la obesidad infantil y aumenta el riesgo de enfermedades cerebrocardiovascular. También se evidencia que disminuye la capacidad física y la calidad de vida de niños y adolescentes. Los aspectos psicológicos también se ven afectados, lo que influye en el rendimiento académico, que es inferior al de los niños sanos. Así pues, es importante un diagnóstico precoz del SAHS pediátrico, de modo que se eviten las alteraciones asociadas.

CIGB-300 is a pro-apoptotic casein kinase 2 inhibitor peptide with potential anticancer action. An open-label and dose scaling Phase I trial was carried out to investigate the peptide tumor uptake, pharmacokinetics, toxicity, and levels of a CIGB-300 response biomarker in patients with cervical cancer stage IB2/II. Fourteen patients were included; six of them received 35 mg, 6 received 70 mg and the two remaining patients received 245 mg of CIGB-300 prior chemoradiotherapy. CIGB-300 was applied by intratumor injections during 5-consecutive days. For pharmacokinetic and biodistribution studies, the peptide was radiolabeled with 99m Tc in the first administration and whole body gammagraphy and plasma testing were done during 48 h. Data showed that the maximum tolerated dose was 70 mg for CIGB-300 in this clinical setting. Furthermore, an allergic-like syndrome was identified as the dose limiting toxicity, which was well-correlated with plasmatic histamine levels. Importantly, the mean tumor uptake was 14.9 mg and 10.4 mg for CIGB-300 doses of 35 and 70 mg, respectively. Also, the kidneys were the main target organ for drug elimination. Finally, treatment with CIGB-300 significantly reduced the B23/nucleophosmin levels in tumor specimens. CIGB-300 meets potentialities to be tested in future trials in a neoadjuvant setting prior to chemoradiotherapy in cervical cancer.