Household-level effects of seasonal malaria chemoprevention in the Gambia.

BACKGROUND: In 2022 the WHO recommended the discretionary expansion of the eligible age range for seasonal malaria chemoprevention (SMC) to children older than 4 years. Older children are at lower risk of clinical disease and severe malaria so there has been uncertainty about the cost-benefit for national control programmes. However, emerging evidence from laboratory studies suggests protecting school-age children reduces the infectious reservoir for malaria and may significantly impact on transmission. This study aimed to assess whether these effects were detectable in the context of a routinely delivered SMC programme. METHODS: In 2021 the Gambia extended the maximum eligible age for SMC from 4 to 9 years. We conducted a prospective population cohort study over the 2021 malaria transmission season covering 2210 inhabitants of 10 communities in the Upper River Region, and used a household-level mixed modelling approach to quantify impacts of SMC on malaria transmission. RESULTS: We demonstrate that the hazard of clinical malaria in older participants aged 10+ years ineligible for SMC decreases by 20% for each additional SMC round per child 0-9 years in the same household. Older inhabitants also benefit from reduced risk of asymptomatic infections in high SMC coverage households. Spatial autoregression tests show impacts are highly localised, with no detectable spillover from nearby households. CONCLUSIONS: Evidence for the transmission-reducing effects of extended-age SMC from routine programmes implemented at scale has been previously limited. Here we demonstrate benefits to the entire household, indicating such programmes may be more cost-effective than previously estimated.

Seasonal malaria chemoprevention (SMC) is the provision of monthly, preventative, anti-malaria medication to young children at times when they are most at risk of severe disease. Recently the World Health Organisation recommended expanding SMC to children older than 4 years. Older children with malaria typically remain symptomless so the advantages were unclear. However, laboratory evidence suggests this group continues to transmit malaria to others. We conducted a population study in 2021 in 10 communities in the Gambia where SMC was extended to all children up to 9 years of age for the first time. We found household members aged over 9 years were less likely to get clinical disease when most young children in the same household did receive SMC. This suggests an added protection of SMC for those who do not receive it, potentially increasing cost-effectiveness.

Understanding and maximising the community impact of seasonal malaria chemoprevention in Burkina Faso (INDIE-SMC): study protocol for a cluster randomised evaluation trial.

INTRODUCTION: Seasonal malaria chemoprevention (SMC) involves repeated administrations of sulfadoxine-pyrimethamine plus amodiaquine to children below the age of 5 years during the peak transmission season in areas of seasonal malaria transmission. While highly impactful in reducing Plasmodium falciparum malaria burden in controlled research settings, the impact of SMC on infection prevalence is moderate in real-life settings. It remains unclear what drives this efficacy decay. Recently, the WHO widened the scope for SMC to target all vulnerable populations. The Ministry of Health (MoH) in Burkina Faso is considering extending SMC to children below 10 years old. We aim to assess the impact of SMC on clinical incidence and parasite prevalence and quantify the human infectious reservoir for malaria in this population. METHODS AND ANALYSIS: We will perform a cluster randomised trial in Saponé Health District, Burkina Faso, with three study arms comprising 62 clusters of three compounds: arm 1 (control): SMC in under 5-year-old children, implemented by the MoH without directly observed treatment (DOT) for the full course of SMC; arm 2 (intervention): SMC in under 5-year-old children, with DOT for the full course of SMC; arm 3 (intervention): SMC in under 10-year-old children, with DOT for the full course of SMC. The primary endpoint is parasite prevalence at the end of the malaria transmission season. Secondary endpoints include the impact of SMC on clinical incidence. Factors affecting SMC uptake, treatment adherence, drug concentrations, parasite resistance markers and transmission of parasites will be determined. ETHICS AND DISSEMINATION: The London School of Hygiene & Tropical Medicine's Ethics Committee (29193) and the Burkina Faso National Medical Ethics Committee (Deliberation No 2023-05-104) approved this study. The findings will be presented to the community; disease occurrence data and study outcomes will also be shared with the Burkina Faso MoH. Findings will be published irrespective of their results. TRIAL REGISTRATION NUMBER: NCT05878366.

Sexual-biased necroinflammation is revealed as a predictor of bevacizumab benefit in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is a highly malignant brain tumor that affects men more often than women. In addition, the former shows a poorer survival prognosis. To date, the reason for this sex-specific aggressiveness remains unclear. Therefore, the aim of this study is to investigate tumor processes that explain these sex differences. METHODS: This was a retrospective study of GBM patients which was stratified according to sex. A cohort with 73 tumors was analyzed with immunohistochemistry, RNA-seq and RT-qPCR to characterize differences in vascular and immunological profiles. Transcriptomic profiling, gene set enrichment analysis, and pathway enrichment analysis were used for discovering molecular pathways predominant in each group. We further investigated the therapeutic effect of bevacizumab (vascular endothelial growth factor A (VEGFA) blocking antibody) in a retrospective GBM cohort (36 tumors) based on sex differences. RESULTS: We found that under hypoxic tumor conditions, 2 distinct tumor immuno-angiogenic ecosystems develop linked to sex differences and ESR1 expression is generated. One of these subgroups, which includes male patients with low ESR1 expression, is characterized by vascular fragility associated with the appearance of regions of necrosis and high inflammation (called necroinflamed tumors). This male-specific tumor subtype shows high inflammation related to myeloid-derived suppressor cells infiltration. Using this stratification, we identified a possible group of patients who could respond to bevacizumab (BVZ) and revealed a genetic signature that may find clinical applications as a predictor of those who may benefit most from this treatment. CONCLUSIONS: This study provides a stratification based on the sexual differences in GBM, which associates the poor prognosis with the presence of immunosuppressive myeloid cells in the necrotic areas. This new stratification could change the current prognosis of GBM and identifies those who respond to BVZ treatment.

Maternal and obstetric outcomes after Ex-Utero Intrapartum Treatment (EXIT): a single center experience.

BACKGROUND: The Ex-utero Intrapartum Treatment (EXIT) is a procedure developed to manage a range of fetal conditions, aiming to ensure the maintenance of neonatal airway and preserving the feto-placental circulation. Its goal is to enhance the neonatal ability to successfully transition and adapt to postnatal life, thereby reducing perinatal morbidity and mortality. However, EXIT has been associated with a high risk of maternal complications. This paper provides an overview of the indications and characteristics of the EXIT procedure, as well as the obstetric outcomes and maternal complications. METHODS: A retrospective analysis was conducted on a cohort of patients undergoing EXIT at our center between January 2007 and December 2022. Maternal outcomes, including demographic information, data related to the surgical procedure, surgical complications, and postoperative complications were analyzed. To assess the severity of the surgical complications, a modified Clavien-Dindo classification was used. Comparative analysis was performed by randomly selecting a sample from elective cesarean deliveries performed at our center. RESULTS: A total of 34 EXIT procedures were performed. According to the modified Clavien-Dindo classification, we observed no major complications, while minor maternal complications were present in 2.94% of cases. Compared to elective cesarean deliveries (n = 350), there were no significant differences in terms of maternal complications, highlighting the similarity observed in the mean decrease in postoperative hemoglobin (1.15 g/dL in EXIT vs. 1.2 g/dL in elective cesarean deliveries, p = 0.94). In EXIT group, there was a higher rate of polyhydramnios (26.47% vs 6.59%, p < 0.001), as well as the need for amnioreduction (14.71% vs 0%, p = 0.001) and preterm delivery (32.35% vs 6.02%, p = 0.001). There were no cases of endometritis, post-procedural fever, or abruptio placentae following EXIT. CONCLUSIONS: EXIT can be considered a safe procedure when performed under adequate conditions, including appropriate uterine access and proper anesthetic management. In our series, EXIT procedure was not associated with a higher incidence of maternal complications when compared to elective cesarean delivery. TRIAL REGISTRATION: Retrospectively registered.

Maternal and Neonatal Outcomes After Ex-Utero Intrapartum Treatment for Congenital Diaphragmatic Hernia: A Case Series.

INTRODUCTION: Despite advances in neonatal intensive care, fetuses with congenital diaphragmatic hernia (CDH) remain to have a poor prognosis. Exclusive postnatal treatment is inadequate in patients with moderate CDH (observed than expected lung-to-head ratio [O/E LHR] 26-45%) and can lead to respiratory failure at birth, requiring extracorporeal membrane oxygenation in 75% of cases. An ex-utero intrapartum treatment (EXIT) procedure may be beneficial in these cases, improving the fetal-neonatal transition. MATERIAL AND METHODS: We review all pregnancies with fetal isolated left CDH with moderate O/E LHR delivered by EXIT in our center from January 2007 to December 2022. Maternal and neonatal variables were analyzed. As primary outcomes, we included neonatal survival and mortality rates, surgical and infectious complications, uterine scar dehiscence, and blood loss during EXIT. As secondary outcomes, we studied recurrences of the diaphragmatic defect, long-term evolution, subsequent pregnancies, and mode of delivery. RESULTS: A total of 14 patients were delivered by the EXIT procedure, with a neonatal survival rate of 85.7%. All these children had optimal physical and neurocognitive development and no pulmonary morbidity. We found no major complications and 7.1% of minor maternal complications. There were no cases of surgical wound infection or endometritis. The median decrease in hemoglobin during the EXIT procedure was 1.9 mg/dL, and only one case required postoperative transfusion. Two out of the 14 women became pregnant again, and both pregnancies were uneventful. CONCLUSIONS: In our series, the EXIT procedure allows for adequate airway management associated with a high neonatal survival rate in patients with moderate O/E LHR CDH, with a low rate of neonatal and maternal complications.

Anaplastic large cell lymphomas with the 6p25.3 rearrangement are a heterogeneous group of tumours with a diverse molecular background.

ALK-negative anaplastic large cell lymphoma (ALCL) cases with 6p25.3 rearrangement are characterized by peculiar morphological and immunohistochemical features compare to 6p25.3-negative ALK-negative ALCL cases. A subgroup of 6p25.3-positive ALK-negative ALCL cases show the t(6,7) (p25.3;q32.3) rearrangement. Aims: To analyse the differences between 6p25.3-rearranged cases with and without t(6,7) (p25.3;q32.3). Using RNA-sequencing we studied a series of 17 samples showing 6p25.3-rearrangement, identified by FISH, consisting of seven systemic and eight primary cutaneous cases including two examples of secondary skin involvement by systemic ALCL. RNA-sequencing exclusively detected a translocation involving a gene in the 6p25.3 region (either IRF4 or DUSP22) in 7/14 cases (50%). In six of these seven cases the partner proved to be the LINC-PINT region in chromosome 7, while an EXOC2::DUSP22 rearrangement was found in one case. All cases but one were primary cutaneous ALCLs. They all were CD3 positive and BCL2 negative, while most of them expressed p-STAT3. On the contrary, cases without the t(6,7) (p25.3;q32.3) were mainly systemic (71%, 5/7) against just two pcALCL. In general, they lose CD3 (50% positive) and p-STAT3 (25% positive) expression, being all of them BCL2 positive. Moreover, in 60% of them other gene fusions were found. At the transcriptional level, they were characterized by the overexpression of TCF3 (TCF7L1/E2A), DLL3, CD58 and BCL2 genes 75%(6/8) of pcALCL with 6p25.3 rearrangement featured the so-called "biphasic morphologic pattern, which was not found in cutaneous involvement from systemic ALCL. 83% (5/6) of the pcALCL cases with the "biphasic morphologic pattern" showed the t(6,7) (p25.3;q32.3) rearrangement. ALK-negative ALCL cases with 6p25.3 rearrangement are a subgroup of tumours that are heterogeneous with respect to the presence or absence of the t(6,7) (p25.3;q32.3) translocation.

Advanced immunotherapies for glioblastoma: tumor neoantigen vaccines in combination with immunomodulators.

Glial-origin brain tumors, including glioblastomas (GBM), have one of the worst prognoses due to their rapid and fatal progression. From an oncological point of view, advances in complete surgical resection fail to eliminate the entire tumor and the remaining cells allow a rapid recurrence, which does not respond to traditional therapeutic treatments. Here, we have reviewed new immunotherapy strategies in association with the knowledge of the immune micro-environment. To understand the best lines for the future, we address the advances in the design of neoantigen vaccines and possible new immune modulators. Recently, the efficacy and availability of vaccine development with different formulations, especially liposome plus mRNA vaccines, has been observed. We believe that the application of new strategies used with mRNA vaccines in combination with personalized medicine (guided by different omic's strategies) could give good results in glioma therapy. In addition, a large part of the possible advances in new immunotherapy strategies focused on GBM may be key improving current therapies of immune checkpoint inhibitors (ICI), given the fact that this type of tumor has been highly refractory to ICI.

Outcomes and bioethical implications of lymphadenectomy in mastectomized patients: Importance and indication of ultrasound-guided fine-needle aspiration biopsy / Resultados e implicaciones bioéticas de la linfadenectomía en pacientes mastectomizadas: Importancia y recomendación de biopsia por aspiración con aguja fina guiada por ecografía / Resultados e implicações bioéticas da linfadenectomia em pacientes mastectomizadas: Importância e recomendação da biópsia aspirativa com agulha fina guiada por ultrassom

Introduction: Lymph node involvement is the main prognostic factor in breast cancer. Mastectomized patients usually undergo lymphadenectomy (LA) of micrometastatic sentinel lymph nodes (SLNs) despite the evidence of AMAROS trial to replace this therapy with radiotherapy in select cases. Objective: Demonstrate the ability of ultrasonography to detect non-metastatic or micrometastatic SLNs. Materials and methods: 132 patients who underwent mastectomy were evaluated. Ultrasound-guided fine-needle aspiration biopsy (FNAB) was indicated for suspicious lymph nodes. LA and SNL biopsy (SLNB) were performed in patients with positive and negative FNAB, respectively. LA was performed in FNAB positive or SLNB positive cases, except in the presence of isolated tumor cells and micrometastatic SLNs. The tumor burden after LA in patients with negative FNAB and positive SLNB was measured; the presence of two or fewer positive SLNs was considered a low burden. Results: Sensitivity of FNAB for detecting positive lymph nodes in patients with a high tumor burden was 93% and specificity was 84%. Positive (PPV) and negative predictive value (NPV) were 60% and 79%, respectively. Conclusions: LA could have been avoided in 90% of mastectomized patients with negative FNAB and a low tumor burden who met the AMAROS criteria with a high NPV (79%).

Introducción: La afectación ganglionar es el principal factor pronóstico en cáncer de seno. Generalmente, pacientes mastectomizadas se somenten a linfadenectomia (LA) de ganglios linfáticos centinela micrometastásicos (GLCs), a pesar de la evidencia del ensayo AMAROS en ciertos casos para reemplazarla con radioterapia. Objetivo: Demostrar la importancia de la ecografía para detectar GLCs no metastásicos o micrometastásicos. Materiales y métodos: Se evaluaron132 pacientes sometidas a mastectomía. Se recomendó biopsia aspirativa con aguja fina (BAAF) por ultrasonido para ganglios linfáticos sospechosos. Se realizó Biopsia LA y biopsia de GLCs (BGLC) en pacientes con BAAF positiva y negativa, respectivamente. En casos positivos de BAAF o BGLC se ejecutó LA, excepto en presencia de células tumorales aisladas y GLCs. Se evaluó la carga tumoral posterior a LA en pacientes con BAAF negativa y BGLC positiva. La presencia de dos o menos GLC positivos se consideró carga baja. Resultados: La sensibilidad de BAAF para detectar nódulos linfáticos positivos en pacientes con alta carga tumoral fue del 93%; la especificidad fue del 79%. Valores predictivos positivo (60%) y negativo (79%). Conclusiones: Se podría haber evitado LA en 90% de pacientes mastectomizadas con BAAF negativa y baja carga tumoral que cumplían criterios AMAROS con alto VPN (79%).

Introdução: O comprometimento dos gânglios é o principal fator prognóstico no câncer de mama. Geralmente, pacientes mastectomizadas são submetidas a linfadenectomia (LA) de gânglios linfáticos sentinelas de micrometástases (GLSs), apesar da evidência do estudo AMAROS em certos casos para substituí-la por radioterapia. Objetivo: Demonstrar a importância da ultrassonografia na detecção de GLSs não metastáticos ou micrometástase. Materiais e métodos: Foram avaliadas 132 pacientes submetidas à mastectomia. A biópsia aspirativa com agulha fina (BAAF) ultrassônica foi recomendada para gânglios linfáticos suspeitos. A biópsia LA e a biópsia do GLSs (BGLS) foram realizadas em pacientes com BAAF positivo e negativo, respectivamente. Nos casos positivos de BAAF ou BGLS, a LA foi realizada, exceto na presença de células tumorais isoladas e GLSs. A carga tumoral após a LA foi avaliada em pacientes com BAAF negativa e BGLS positiva. A presença de dois ou menos GLS positivos foi considerada carga baixa. Resultados: A sensibilidade do BAAF para detectar linfonodos positivos em pacientes com alta carga tumoral foi de 93%; a especificidade foi de 79%. Valores preditivos positivos (60%) e negativos (79%). Conclusões: a LA poderia ter sido evitada em 90% das pacientes mastectomizadas com BAAF negativa e baixa carga tumoral que preencheram os critérios AMAROS com alto VPN (79%).

Inguinal Sentinel Lymph Node in a Patient With Recurrent Breast Cancer.

ABSTRACT: Sentinel lymph node biopsy is the standard of care for axillary staging in early, clinically node-negative breast cancer. The lymphatic pathways could be altered after receiving axillary treatments such as radiation and/or axillary lymph node dissection. We report a case of inguinal and contralateral axilla SLNs in breast cancer recurrence.

A Rare Case of Drug-induced Erectile Dysfunction with Adalimumab and Certolizumab Solved after Switch to Ustekinumab in a Crohn's Disease Patient.

BACKGROUND: Crohn Disease (CD) is an intestinal inflammatory condition characterized by a complex pathogenesis, with elevated levels of inflammatory cytokines. Adalimumab and certolizumab are two biologic drugs inhibiting TNF-α. OBJECTIVE: We report the first case of a probable relationship, according to Naranjo causality assessment score, between two consecutive treatments with TNF-α inhibitors and induced erectile dysfunction (ED), that disappeared after switching to another biologic drug (ustekinumab). CASE PRESENTATION: This case report describes a possible and important association of two TNF-α inhibitors (certolizumab and adalimumab) and ED in a male patient with CD, with resolution after switching to Ustekinumab (anti-interleukin 12 and 23 biologic drug). A 65 years old man experienced erectile dysfunction during treatment with an anti-TNF. The adverse effect disappeared after discontinuation of the drug. All necessary urologic exams were carried out. Adalimumab was replaced by certolizumab and sexual disfunction symptoms appeared again, improving typically at the end of treatment periods and getting worse with each new dose. RESULTS: Switching to ustekinumab lead to a resolution of the erectile dysfunction. CONCLUSION: We describe for the first time a sexual dysfunction possibly due to two similar anti TNF drugs and its resolution after the switch to another similar but different drug, highlighting the potential difference between biologic drugs.

High-throughput RNA sequencing transcriptome analysis of ABC-DLBCL reveals several tumor evasion strategies.

Activated B-cell (ABC) lymphoma, a distinct molecular entity within diffuse large B-cell lymphoma (DLBCL), remains highly incurable, showing a worse response to standard immunochemotherapy. The discouraging results obtained in several clinical trials using proteasome inhibitors, tyrosine kinase inhibitors, or immunomodulators, lead to an intense search for new, potentially druggable biomarkers in DLBCL. In this study, we designed an experimental strategy for DLBCL to discover high- and low-abundance RNA-seq-derived transcripts involved in the oncogenic phenotype in patients diagnosed with ABC-DLBCL. Based on the results of a comparative analysis, 79 DE genes and two enriched gene sets related to metabolism and immunity were selected. Genes related to drug resistance, anti-inflammatory response, and tumor-cell dissemination were found to be up-regulated, while tumor suppressor genes were down-regulated. Then, we searched for the perturbagens most suitable for gene expression profiling (GEP) by iLINCS-CMap. Herein, we present a novel experimental approach that connects the omics signature of DLBCL with potential drugs for more accurate treatments.

GOECP/SEOR clinical guidelines on radiotherapy for malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare tumor with poor prognosis and rising incidence. Palliative care is common in MPM as radical treatment with curative intent is often not possible due to metastasis or extensive locoregional involvement. Numerous therapeutic advances have been made in recent years, including the use of less aggressive surgical techniques associated with lower morbidity and mortality (e.g., pleurectomy/decortication), technological advancements in the field of radiotherapy (intensity-modulated radiotherapy, image-guided radiotherapy, stereotactic body radiotherapy, proton therapy), and developments in systemic therapies (chemotherapy and immunotherapy). These improvements have had as yet only a modest effect on local control and survival. Advances in the management of MPM and standardization of care are hampered by the evidence to date, limited by high heterogeneity among studies and small sample sizes. In this clinical guideline prepared by the oncological group for the study of lung cancer of the Spanish Society of Radiation Oncology, we review clinical, histologic, and therapeutic aspects of MPM, with a particular focus on all aspects relating to radiotherapy, including the current evidence base, associations with chemotherapy and surgery, treatment volumes and planning, technological advances, and reradiation.

Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.

Natural phenolic compounds found in food have demonstrated interesting preventive and therapeutic effects on a large variety of pathologies. Indeed, some of them, such as resveratrol (RES), have been examined in clinical trials. Nevertheless, their success has been scarce mainly due to their low bioavailability. In this study, we found serendipitously that O-silyl RES derivatives exerted a better neuroprotective activity than resveratrol itself and decided to explore them as potential drugs for neurodegenerative and neurological diseases. We have also designed and prepared a series of O-silyl RES prodrugs to improve their bioavailability. We found that di-triethylsilyl and di-triisopropylsilyl RES derivatives were better in vitro neuroprotective and anti-inflammatory agents than RES. Among these derivatives and their corresponding acyl-, glycosyl- and carbamoyl-prodrugs, 3,5-triethylsilyl-4'-(6″-octanoylglucopyranosyl) resveratrol 26 showed the best profile on toxicity and neuroprotective activity in zebra fish embryo. Compound 26 was also capable of reducing the loss of motor coordination in a 3-nitropropionic acid mice model of Huntington's disease, in a similar way to RES. However, 26 diminished pro-inflammatory cytokine IL-6 to a higher extent than RES and improved the latency to fall in the rotarod test by 10% with respect to RES. Finally, we investigated 26 and RES as potential treatments on an experimental autoimmune encephalomyelitis (EAE) multiple sclerosis mice model. We observed that, in a therapeutic regimen, 26 significantly diminished the progression of EAE severity and reduced the percentage of animals with moderate to severe clinical score, whereas RES showed no improvement.

Neonatal cystic fibrosis screening: Analysis and differences in immunoreactive trypsin levels in newborns with a positive screen.

INTRODUCTION: Neonatal cystic fibrosis (CF) screening has enabled the disease to be diagnosed early, and is a determining factor in the increase in survival of these patients. Its main disadvantage is its low specificity and elevated number of false positives. The aim of this study is to analyse the differences in immunoreactive trypsin (IRT) between the different groups of newborns (NB) with a positive neonatal screen depending on whether they were healthy, healthy carriers, affected by CF, or CFSPID (Cystic Fibrosis Screen Positive, Inconclusive Diagnosis). MATERIAL: Retrospective analytical study of the concentrations of IRT in NB with a positive neonatal screen for CF born in a tertiary hospital during an 8-year period. RESULTS: A total of 790 NB with a positive neonatal screen for CF were analysed. Of these 86.3% were term, 53% girls, and 11.8% were admitted. The mean IRT value was 79.16 ng/mL (range 60-367). Significantly higher concentrations of IRT were found in those affected by CF compared to the other groups (P < .001). There were higher levels in large prematures (P = .007) and admitted patients (P = .002). There were no differences as regards gender or season. There was a direct correlation of 64% (P = .001) between IRT and sweat test in those affected by CF and CFSPID. A cut-off value of IRT for the diagnosis of CF was calculated from the ROC curve (76.2 ng/mL (S = 95.7%, Sp = 64.5%). CONCLUSIONS: NB with CF have significantly higher levels of IRT than healthy ones, or carriers and CFSPID. Prematurity and hospital admission may also have an influence. A higher IRT value is associated with a higher level in the sweat test.

Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

Breast cancer is the most frequent cancer and the leading cause of cancer death in women. Oxidative stress and the generation of reactive oxygen species (ROS) have been related to cancer progression. Compared to their normal counterparts, tumor cells show higher ROS levels and tight regulation of REDOX homeostasis to maintain a low degree of oxidative stress. Traditionally antioxidants have been extensively investigated to counteract breast carcinogenesis and tumor progression as chemopreventive agents; however, there is growing evidence indicating their potential as adjuvants for the treatment of breast cancer. Aimed to elucidate whether antioxidants could be a reality in the management of breast cancer patients, this review focuses on the latest investigations regarding the ambivalent role of antioxidants in the development of breast cancer, with special attention to the results derived from clinical trials, as well as their potential use as plausible agents in combination therapy and their power to ameliorate the side effects attributed to standard therapeutics. Data retrieved herein suggest that antioxidants play an important role in breast cancer prevention and the improvement of therapeutic efficacy; nevertheless, appropriate patient stratification based on "redoxidomics" or tumor subtype is mandatory in order to define the dosage for future standardized and personalized treatments of patients.

Music-Based Interventions in Paediatric and Adolescents Oncology Patients: A Systematic Review.

BACKGROUND: The implications of cancer and its medical treatment are traumatic, highly stressful and have great psychosocial impact. Therefore, a comprehensive treatment is essential and music-based interventions can play an important role. The objective of this study is to summarise research that assesses the effects of music therapy in paediatric and adolescent patients with cancer during the process of the disease. METHODS: A systematic review conducted following PRISMA's statements. An electronic search of the literature was carried out in the following databases: PubMed, Cochrane, Dialnet, Scopus, IDICEs CSIC and Science Direct. Original studies that conducted music-based interventions with oncology patients between 0 to 18 years old were included. RESULTS: 11 studies were finally included in the review. The sample consisted of two quasi-experimental studies, five randomised clinical controlled trials, one non-randomised controlled trial, one study that involved qualitative and quantitative analysis methods, one descriptive study and one observational study. CONCLUSIONS: Music-based interventions decrease anxiety, perceived pain and depression symptoms and improve state of mind, self-esteem and quality of life of paediatric and adolescent patients with cancer. Moreover, they decrease heart rate, respiratory rate and blood pressure and encourage patients to use adaptive coping strategies.

Drug Repurposing for Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer which presents a high rate of relapse, metastasis, and mortality. Nowadays, the absence of approved specific targeted therapies to eradicate TNBC remains one of the main challenges in clinical practice. Drug discovery is a long and costly process that can be dramatically improved by drug repurposing, which identifies new uses for existing drugs, both approved and investigational. Drug repositioning benefits from improvements in computational methods related to chemoinformatics, genomics, and systems biology. To the best of our knowledge, we propose a novel and inclusive classification of those approaches whereby drug repurposing can be achieved in silico: structure-based, transcriptional signatures-based, biological networks-based, and data-mining-based drug repositioning. This review specially emphasizes the most relevant research, both at preclinical and clinical settings, aimed at repurposing pre-existing drugs to treat TNBC on the basis of molecular mechanisms and signaling pathways such as androgen receptor, adrenergic receptor, STAT3, nitric oxide synthase, or AXL. Finally, because of the ability and relevance of cancer stem cells (CSCs) to drive tumor aggressiveness and poor clinical outcome, we also focus on those molecules repurposed to specifically target this cell population to tackle recurrence and metastases associated with the progression of TNBC.

An Unusual Case of Allergic Reaction to Anakinra in a Patient with Tumor Necrosis Factor Receptor-1 Associated Periodic Syndrome (TRAPS) and Subsequent Canakinumab Treatment.

Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is a rare hereditary systemic autoinflammatory disease (SAID). Treatment is based on corticosteroids, but often requires the addition of a biologic drug (anti-TNF agent, IL-1 receptor antagonist, etc) to achieve symptom control. The addition of the second drug is not clearly defined and must take into account the characteristics and preferences of the patient. We describe a patient with TRAPS and an allergic reaction to anakinra which was difficult to manage clinically while alternative treatment was being identified. LEARNING POINTS: Treatment of tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) often requires adding a biologic drug to corticosteroids to achieve the best efficacy.Currently, IL-1 receptor antagonists are considered the first line of treatment in TRAPS.The most frequent adverse effect of anakinra is a reaction at the injection site.Canakinumab has shown better response compared to placebo in the treatment of TRAPS.

Actin and Nuclear Envelope Components Influence Ectopic Recombination in the Absence of Swr1.

The accuracy of most DNA processes depends on chromatin integrity and dynamics. Our analyses in the yeast Saccharomyces cerevisiae show that an absence of Swr1 (the catalytic and scaffold subunit of the chromatin-remodeling complex SWR) leads to the formation of long-duration Rad52, but not RPA, foci and to an increase in intramolecular recombination. These phenotypes are further increased by MMS, zeocin, and ionizing radiation, but not by double-strand breaks, HU, or transcription/replication collisions, suggesting that they are associated with specific DNA lesions. Importantly, these phenotypes can be specifically suppressed by mutations in: (1) chromatin-anchorage internal nuclear membrane components (mps3∆75-150 and src1∆); (2) actin and actin regulators (act1-157, act1-159, crn1∆, and cdc42-6); or (3) the SWR subunit Swc5 and the SWR substrate Htz1 However, they are not suppressed by global disruption of actin filaments or by the absence of Csm4 (a component of the external nuclear membrane that forms a bridging complex with Mps3, thus connecting the actin cytoskeleton with chromatin). Moreover, swr1∆-induced Rad52 foci and intramolecular recombination are not associated with tethering recombinogenic DNA lesions to the nuclear periphery. In conclusion, the absence of Swr1 impairs efficient recombinational repair of specific DNA lesions by mechanisms that are influenced by SWR subunits, including actin, and nuclear envelope components. We suggest that these recombinational phenotypes might be associated with a pathological effect on homologous recombination of actin-containing complexes.