Search Results for: L’ereditarietà di 12 tipi di cancro

Per nati 1990 rischio doppio di cancro colon

Stroke, Ahead of Print. BACKGROUND:Epigenetic modifications 5-methylcytosine and 5-hydroxymethylcytosine in DNA regulate neuronal survival under ischemic stress. We previously showed that TET3 (ten-eleven translocation 3)–mediated 5-methylcytosine to 5-hydroxymethylcytosine conversion induces neuroprotective gene transcription after stroke. As TET3 neuronal isoform lacks the DNA-binding domain, how TET3 drives 5-hydroxymethylcytosine–mediated transcriptional induction in the ischemic brain remains unclear. Long noncoding RNAs (lncRNAs) act as structural scaffolds to recruit chromatin-modifying proteins and other RNAs to specific genomic loci. However, whether TET3 requires an lncRNA to drive DNA hydroxymethylation in the ischemic brain is unknown.METHODS:Adult male and female mice were subjected to transient middle cerebral artery occlusion. TET3-bound lncRNAs were immunoprecipitated from peri-infarct cortex, and TILR (TET3-interacting lncRNA; AK020504) identified was inhibited with small interfering RNA injected at 5 minutes of reperfusion. Ascorbate was administered at 30 minutes of reperfusion to induce TET3 activity. Poststroke DNA hydroxymethylation was assessed with hydroxymethylation DNA immunoprecipitation sequencing, and sensorimotor deficits, and infarct volume were evaluated between days 1 and 7 of reperfusion.RESULTS:TILR binds to TET3 with high affinity and was significantly upregulated in the peri-infarct cortex at 12 hours of reperfusion. Knockdown of TILR increased the infarct volume and reduced the motor function recovery after transient middle cerebral artery occlusion, in a TET3-dependent manner. On contrary, TET3 activation by ascorbate decreased brain damage and improved motor function recovery after ischemia. However, ascorbate-induced postischemic protection was abrogated by TILR knockdown. Genome-wide profiling showed that ascorbate increases the number of differentially hydroxymethylated regions in the poststroke genome, a neuroprotective effect that is reversed by TILR knockdown. Moreover, TILR inhibition significantly reduced the DNA hydroxymethylation in the intergenic regions associated with enhancers, super enhancers, and the promoters of other lncRNAs, microRNAs, and PIWI-interacting RNAs.CONCLUSIONS:These findings highlight the essential role of TILR in TET3-mediated 5-hydroxymethylcytosine-dependent epigenetic reprogramming in the ischemic brain.

Uno studio prospettico pubblicato su Pain and Therapy condotto presso il centro regionale per le cure palliative dell’Ospedale La Maddalena di Palermo ha analizzato, a distanza di 12 anni da una precedente indagine, le strategie di prescrizione degli oppioidi e l’efficacia analgesica in pazienti ricoverati in un’Unità di Cure Palliative Acute (APCU). I risultati mostrano che un approccio intensivo e personalizzato consente un controllo efficace del dolore senza necessità di aumentare l’equivalente in morfina orale (OME), e sottolineano l’importanza di una gestione esperta nella terapia del dolore oncologico.

Un nuovo inibitore selettivo dell’aldosterone, baxdrostat, ha mostrato in uno studio di Fase III un’efficace riduzione della pressione arteriosa sistolica a 12 settimane, aprendo nuovi scenari terapeutici per pazienti con ipertensione non controllata o resistente.

Dal melanoma al tumore del polmone, dal cancro al seno triplo negativo a quello del colon-retto e della vescica: sono sempre più numerosi i tumori per cui la somministrazione dell’immunoterapia neoadiuvante, cioè del trattamento prima dell’intervento chirurgico, mostra evidenze di maggiore efficacia. Questa nuova evoluzione dell’immunoterapia è al centro della seconda edizione di “I.N.N.O.VA.T.E. – International Neoadjuvant Immunotherapy Across Cancers”, al via oggi, e fino a domani, a Napoli.

L’Agenzia Italiana del Farmaco (Aifa) ha riconosciuto la rimborsabilità di un’ulteriore indicazione terapeutica per enzalutamide, sulla base dei risultati dello studio di Fase 3 EMBARK. Con questa autorizzazione enzalutamide diventa il primo ed unico inibitore del segnale del recettore degli androgeni che ha ottenuto la rimborsabilità per il trattamento di uomini adulti con cancro della prostata non metastatico ormono-sensibile (nmHSPC) con recidiva biochimica (BCR) ad alto rischio non idonei alla radioterapia di salvataggio

Introduction
Distal radius fractures account for one-fifth of all fractures in the active elderly population and may cause chronic pain, loss of hand function and reduced work productivity, imposing a significant socioeconomic burden. Most are initially treated with closed reduction and casting, but 30% subsequently require surgery due to insufficient realignment. The current approaches for analgesia for closed reduction are suboptimal. A brachial plexus nerve block provides complete pain relief and muscle relaxation distal to the elbow, potentially creating better conditions for realignment of the fractured bone ends. This may ultimately translate into reduced need for surgery and result in better functional outcomes and fewer complications compared to a haematoma block, which is the current standard care in Denmark.

Methods and analysis
The BLOCK Trial is an investigator-initiated, parallel-group, allocation-concealed, outcome assessor and analyst-blinded, superiority, randomised, controlled, clinical multicentre trial performed at 11 Danish emergency departments. Eligible adult patients with a distal radius fracture who need closed reduction will be included and allocated 1:1 to either an ultrasound-guided brachial plexus nerve block or a haematoma block. The primary outcome is the proportion of patients with distal radius fracture surgery 90 days after closed reduction. We will include 1716 participants to detect or discard a relative risk reduction of surgery of 20%. Secondary outcomes include treatment-related complications, patient-reported wrist function, pain during closed reduction and proportion of patients with unacceptable radiographic fracture position immediately after closed reduction.

Ethics and disseminationf
The trial is approved by the Danish Medicines Agency and the Danish Research Ethics Committees (EU CT number: 2024-512191-35-00). All results will be summarised on www.theblocktrial.com, clinicaltrials.gov and euclinicaltrials.eu after publication. Primary and secondary outcome results from 0 to 90 days will be presented in the main article and submitted to a peer-reviewed journal. Results from outcomes on the 12-month follow-up will be presented separately.

Trial registration number
NCT06678438.

Nei bambini affetti da orticaria cronica spontanea, compresi quelli di età inferiore ai 12 anni, omalizumab ha prodotto un elevato tasso di risposta con un profilo di sicurezza accettabile, secondo quanto rilevato da una metanalisi pubblicata sulla rivista Pediatric Allergy and Immunology.

Introduction
Most older adults living in residential aged care facilities (RACFs) have at least one marker of potentially suboptimal prescribing. Pharmacists play a crucial role in medication management, with their effectiveness enhanced by using computerised decision support tools. The Pharmacists Review to Optimise Medicines in Residential Aged Care (PROMPT-RC) study aims to optimise medicine use by providing pharmacists in RACFs with an electronic medicine management app with integrated decision support (AusTAPER App/Pathway) to use as part of medication reviews they undertake.

Methods and analysis
The PROMPT-RC study is a parallel cluster randomised controlled trial design involving Australian RACFs. It will assess if pharmacists’ use of the AusTAPER App/Pathway for medication reviews improves medication regimens for RACF residents compared with usual care. Pharmacists in RACFs randomised to the intervention arm will be trained to use the AusTAPER App/Pathway, which flags potentially inappropriate medicines (PIMs) across a person’s entire medicine regimen. Pharmacists in RACFs randomised to the control arm will not have access to the AusTAPER App/Pathway—they will continue to provide usual care. The primary outcome is the difference in the number of regular medicines between treatment arms at 12 months. Secondary outcomes will measure the number of regular and pro re nata medicines, PIMs, medicine administration times, medicine regimen complexity, use of antipsychotics, antidepressants, and benzodiazepines, quality of life, mortality, instances of physical restraint, and the number of falls, hospitalisations and general practitioner/health professional visits. The cost-effectiveness of the AusTAPER App/Pathway compared with usual care will be calculated. Data collection will occur at baseline, 3, 6, 9 and 12 months postrandomisation and 3 and 6 months prebaseline. We aim to recruit 668 participants to adjust for an estimated 10% loss to follow-up, giving 334 participants in each arm. Data analysis will follow an intention-to-treat approach using a linear mixed model.

Ethics and dissemination
Ethical approval was obtained from The University of Western Australia Human Research Ethics Committee (Reference: 2024/ET000525; approved 14 August 2024). Reciprocal approval was also obtained in other states. This study is registered on the Australian New Zealand Clinical Trials Registry (https://anzctr.org.au). Trial findings will be disseminated through national and international peer-reviewed publications and conferences.

Trial registration number
ACTRN12624001409561.

Background
Despite global improvements in antiretroviral therapy (ART) access for children and adolescents living with HIV (CALHIV), a significant proportion continue to experience unsuppressed viral load (USVL). Limited studies focus on the factors contributing to USVL among CALHIV in the Democratic Republic of the Congo (DRC), especially in the context of evolving treatment landscapes. Understanding these determinants is crucial for enhancing ART outcomes.

Objective
This study aimed to determine the prevalence of USVL and identify factors associated with USVL among CALHIV receiving ART in Lubumbashi, DRC.

Design
A multicentre retrospective cross-sectional study was conducted. Data were gathered using an observational checklist based on assessing patient file data and entered into Microsoft Excel. Analysis was performed using STATA V.16. Variables with a p value of 0.20 from the bivariable analysis were included in a multivariable logistic regression model, and significant variables (p

Objectives
Smoking is a well-established risk factor that exacerbates multiple sclerosis (MS) progression and increases disease activity. Smoking cessation promotion practices of MS clinicians are not meeting the needs of people with MS (pwMS). This study aimed to explore the current practices and barriers faced by MS clinicians in Germany.

Design
A qualitative study design, using semi-structured interviews and thematic analysis.

Setting
Interviews with participants were held online, via telephone or face-to-face at our institute in Hamburg, Germany.

Participants
We recruited eight neurologists and four MS nurses from hospitals, neurology practices and rehabilitation facilities in Germany via purposive and snowball sampling.

Results
We identified 27 codes across four themes: (1) knowledge: the 12 participants demonstrated a satisfactory general knowledge of the negative impacts of smoking on MS (2) current practice: significant variability was reported in the current practices, with some clinicians providing detailed advice while others merely assessing smoking status without further advice or assistance. (3) Barriers: key barriers identified included limited consultation time, perceived lack of patient motivation and insufficient availability of resources, like information material, for effective smoking cessation support. (4) Needs and wishes: participants wished for specific smoking cessation courses to which they could refer patients, as well as information material to use during patient counselling.

Conclusion
The study reveals considerable gaps in the consistency and comprehensiveness of smoking cessation support provided by MS clinicians in Germany. Addressing these gaps through targeted interventions, and improving the availability of information materials could enhance smoking cessation promotion for pwMS.

Ricercatori Biogem, si apre la strada a cure mirate

Ricercatori Biogem, si apre la strada a cure mirate

Stroke, Ahead of Print. BACKGROUND:Poststroke depression affects up to one-third of stroke survivors, significantly impacting recovery and quality of life. However, its pathophysiology remains unclear.METHODS:We analyzed 2 independent, prospective ischemic stroke cohorts (PROSCIS-B [Prospective Cohort of Incident Stroke Berlin] and BAPTISe [Biomarkers and Perfusion-Training-Induced Changes After Stroke]; n=377) enrolled at the Charité Hospital, Germany, to identify brain regions and networks associated with depressive symptoms poststroke. Lesion-symptom mapping assessed associations between lesion location and depressive symptoms measured by the Center for Epidemiological Studies Depression Scale at 6 (BAPTISe) or 12 (PROSCIS-B) months poststroke. Lesion-network mapping evaluated lesion connectivity with brain networks. A mixed-effects model, including cohort as a random effect, assessed the relationship between network similarity (Pearson correlation) and Center for Epidemiological Studies Depression Scale scores. Dice coefficients (DC) quantified spatial overlap with canonical resting-state networks.RESULTS:Lesion-symptom mapping showed no significant associations between lesion location and depressive symptoms. In contrast, lesion-network mapping revealed that lesion connectivity to brain regions including the frontal pole, middle and inferior frontal gyri, inferior temporal gyrus, supramarginal gyrus, angular gyrus, frontal orbital cortex, and thalamus weakly correlated with Center for Epidemiological Studies Depression Scale scores (β, 11.4 [95%CI, 1.8–21.1];P=0.02). These regions overlapped with the frontoparietal (DC=0.28), salience (DC=0.27), and default mode (DC=0.20) networks, as well as a published depression circuit (DC=0.43). However, these findings did not replicate across data sets.CONCLUSIONS:Lesion location alone was not associated with poststroke depression. However, connectivity-based analyses implicated disruption of large-scale brain networks in the development of depressive symptoms. The failure to validate this association across data sets underscores the need for further studies with more comparable patient populations—particularly in terms of stroke severity and harmonized assessment time-points—to confirm these findings and their clinical relevance.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT01363856. URL:https://www.clinicaltrials.gov; Unique identifier: NCT01954797.