Search Results for: Fumo e malattia coronarica: responsabile un singolo gene

A un anno dall’introduzione di ruxolitinib crema, primo trattamento topico specifico per la vitiligine non segmentale, si apre un nuovo capitolo nella gestione clinica della malattia. In occasione dell’incontro scientifico Sharing Real Practice in Vitiligo: Beyond Clinical Data, svoltosi durante il XIV International Congress of Dermatology, sono state condivise esperienze, casi clinici e dati real-world, confrontando l’efficacia terapeutica osservata nella pratica quotidiana con i risultati degli studi di fase 3. 

Nei pazienti con mieloma multiplo ricaduto/refrattario che presentano almeno un’alterazione citogenetica associata a un alto rischio di progressione della malattia, il trattamento con l’anticorpo farmaco-coniugato (ADC) anti-BCMA belantamab mafodotin combinato con bortezomib e desametasone (tripletta BVd) offre un beneficio rispetto alla tripletta standard daratumumab-bortezomib-desametasone (DVd) sia in termini di sopravvivenza libera da progressione (PFS) e sopravvivenza globale (OS) sia in termini di tasso di risposte profonde.

Traversata fino in Croazia. Gattafoni, ‘Difficile come malattia’

La Società Italiana di Medicina Generale e delle Cure Primarie esprime pieno apprezzamento per la decisione comunicata dall’Agenzia Italiana del Farmaco (Aifa) il 30 giugno con cui vengono riclassificate le gliflozine (SGLT2-i: inibitori del trasportatore sodio/glucosio di tipo 2) in fascia A e contestualmente abrogati, per l’intera classe, i Piani Terapeutici per il loro utilizzo nel trattamento del diabete di tipo 2, dello scompenso cardiaco e della malattia renale cronica.

“Storia e valore delle immunoglobuline. L’utilizzo terapeutico nelle immunodeficienze primitive, immunodeficienze secondarie e nella polineuropatia demielinizzante infiammatoria cronica”, è una pubblicazione che è un chiaro esempio di sensibilizzazione e diffusione della cultura del valore dei plasmaderivati: comprendere il valore del dono passa anche attraverso la comprensione della difficoltà di vivere con una patologia rara e cronica come un’immunodeficienza o una malattia ancora più rara, come la polineuropatia demielinizzante infiammatoria cronica (CIDP).

“L’intero Collegio dei Reumatologi Italiani-CReI intende complimentarsi con la collega e componente della nostra Società Antonella Marcoccia per l’approvazione avvenuta in questi giorni del PDTA Sclerosi Sistemica della Regione Lazio”.
Lo dichiara Severino Martin Martin, presidente del CReI in merito all’approvazione e pubblicazione del PDTA dedicato a questa malattia autoimmune.

Presentato ieri a Roma, alla presenza di numerosi rappresentanti istituzionali, autorevoli componenti della comunità scientifica e delle Associazioni, l’XI Rapporto MonitoRare sulla condizione delle persone con malattia rara in Italia. Dal 2015 la Federazione UNIAMO – unico caso in Europa e nel mondo – grazie alla collaborazione con le Istituzioni, raccoglie e analizza i dati disponibili per dare vita a un documento che offre una visione globale del sistema malattie rare, partendo dal punto di vista del persona con malattia rara.

L’idrosadenite suppurativa è una malattia cutanea cronica e infiammatoria che interessa i follicoli piliferi. Si presenta con noduli infiammatori profondi e dolorosi, ascessi, tunnel drenanti (draining tunnels, DTs) e cicatrici, localizzati tipicamente in aree intertriginose del corpo1. Bimekizumab (BKZ), anticorpo monoclonale umanizzato diretto contro le interleuchine IL-17A e IL-17F, ha mostrato risultati promettenti nel trattamento dell’HS. I dati dello studio di estensione in aperto BE HEARD EXT, presentati durante la XIV edizione dell’International Congress of Dermatology confermano un miglioramento clinicamente rilevante delle lesioni e dei tunnel drenanti mantenuto fino a due anni.2

Un paziente con amiloidosi cardiaca da transtiretina (ATTR) oggi in Italia può ricevere diagnosi e cure molto diverse a seconda della Regione in cui vive. Eppure, questa malattia rara, spesso sottovalutata e diagnosticata troppo tardi, necessita di un percorso di cura rapido, personalizzato e multidisciplinare.
Per rispondere a questa sfida, Bistoncini Partners ha realizzato, con il contributo non condizionante di Pfizer, il Position Paper: “L’importanza dei PDTA personalizzati per la gestione del paziente con Amiloidosi da Transtiretina”, che viene oggi presentato nel corso di una conferenza stampa promossa dalla Senatrice Elena Murelli

Circulation, Ahead of Print. BACKGROUND:Direct reprogramming of fibroblasts to cardiomyocytes is a potentially curative strategy for ischemic heart disease. However, current reprogramming strategies require excessive factors due to epigenetic barriers of adult mouse and human fibroblasts. Recently, we identified the epigenetic factor PHF7 from a screen of gene-regulatory factors as the most potent activator of adult fibroblast-to-cardiomyocyte reprogramming in vitro.METHODS:Through in vitro assays coupled with genome-wide studies, we interrogated the ability of PHF7 to induce reprogramming events with minimal reprogramming factors. Using in vivo murine models of myocardial infarction and intramyocardial reprogramming factor delivery coupled with genetic fibroblast lineage tracing, we delivered retroviral PHF7 cocktails to the murine heart and interrogated reprogramming events as well as the acute and chronic functional impact of these cocktails. Deployment of 10X multiomics in vivo generated a combinatorial single-nucleus transcriptomic and epigenomic atlas of PHF7 reprogramming in the infarcted heart.RESULTS:Genome-wide in vitro transcriptomic analyses revealed that addition of PHF7 to Tbx5 or Mef2c and Tbx5 in fibroblasts induced global reprogramming through upregulation of unique cardiac transcriptomes. Further, PHF7 itself upregulated cardiac master regulators when overexpressed in dermal fibroblasts. Delivery of PHF7 cocktails to the infarcted murine heart induced in vivo reprogramming events and improved cardiac function and remodeling in both acute and chronic heart failure. When delivered as a single factor to the infarcted heart, PHF7 improved survival, function, and fibrosis up to 16 weeks after injury. Genetic lineage tracing analyses revealed that PHF7 induced bona fide fibroblast-to-cardiomyocyte reprogramming events in vivo. Comprehensive multiomics of PHF7 cocktails in the infarcted heart exposed the impact of PHF7 on chromatin structure, generating population-level shifts in nonmyocyte and cardiomyocyte cellular identity.CONCLUSIONS:Here, we report the ability of a single epigenetic factor, PHF7, to induce reprogramming and improve cardiac function in the mouse heart following myocardial infarction. Together, these data support the premise that a single factor, when deployed into the infarcted mouse heart, can induce reprogramming events and recover function in the ischemic heart.

Introduction
Artemisinin-based combination therapies (ACTs) remain the WHO-recommended treatment for uncomplicated Plasmodium falciparum malaria. However, the emergence and spread of artemisinin resistance (ART-R) threatens ACT efficacy. ART-R is phenotypically expressed as delayed parasite clearance, which can facilitate ACT partner drug resistance. ART-R has been causally linked to specific mutations in the Pfkelch13 gene.

Methods and analysis
The systematic review and associated meta-analysis aim to determine the correlation between Pfkelch13 (alleles present in the Kelch13 gene region of the P. falciparum parasite) genotypes and clinical and parasitological response to ACTs from a globally representative data set pooling individual patient data (IPD) from eligible published and unpublished studies. The eligibility criteria include Pfkelch13 genotyping results at baseline complemented by individually linked parasitological and clinical assessments following artemisinin-based treatment. The data will be curated, standardised and analysed using this proposed statistical analysis plan (SAP), adhering to PRISMA-IPD (PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Our SAP will apply hierarchical modelling to assess the effect of the P. falciparum parasite Pfkelch13 mutations on parasite clearance half-life and therapeutic efficacy across different regions. This will include study sites as random effects in the model and potential predictors such as age, sex, baseline parasite load and other potential effect modifiers as fixed effects. This analysis will enhance the understanding of the influence of Pfkelch13 mutations on malaria treatment outcomes.

Ethics and dissemination
Data were obtained with informed consent and ethical approvals from the relevant countries and were pseudonymised before curation in the Infectious Diseases Data Observatory (IDDO)/WorldWide Antimalarial Resistance Network (WWARN) repository. Data ownership remains with contributors. This IPD meta-analysis met the Oxford Tropical Research Ethics Committee criteria for waiving ethical review, as it is a secondary analysis of existing pseudonymised data. The resulting peer-reviewed publication and conference proceedings will help strengthen and enhance the efficiency of ART-R surveillance and response and support policy decisions.

PROSPERO registration number
CRD42019133366.

Nelle pazienti con carcinoma mammario metastatico, una nuova terapia ormonale mirata, elacestrant, ha ridotto il rischio di progressione o morte del 45%. L’Agenzia Italiana del Farmaco (AIFA) ha approvato la rimborsabilità di elacestrant per il trattamento di donne in postmenopausa, e di uomini, con carcinoma mammario localmente avanzato o metastatico positivo per i recettori degli estrogeni (ER+) e negativo per la proteina HER2 (HER2-), con una mutazione attivante del gene ESR1, che mostrano progressione della malattia in seguito ad almeno una linea di terapia endocrina comprendente un inibitore delle cicline CDK 4/6.

Background
Gut microbial metabolites are recognised as critical effector molecules that influence the development of colorectal cancer (CRC). Peptidoglycan fragments (PGFs) produced by microbiota play a crucial role in maintaining intestinal homeostasis, but their role in CRC remains unclear.

Objective
Here, we aimed to explore the potential contribution of PGFs in intestinal tumourigenesis.

Design
The relative abundance of peptidoglycan synthase and hydrolase genes was assessed by metagenomic analysis. Specific PGFs in the faeces and serum of CRC patients were quantified using targeted mass spectrometry. The effects of PGF on intestinal tumourigenesis were systematically evaluated using various murine models of CRC and organoids derived from CRC patients. Downstream molecular targets were screened and evaluated using proteome microarray, transcriptome sequencing and rescue assays.

Results
Metagenomic analysis across seven independent cohorts (n=1121) revealed a comprehensive reduction in peptidoglycan synthase gene relative abundance in CRC patients. Targeted mass spectrometry identified significant depletion of a specific PGF, N-acetylmuramic acid (NAM) in CRC patients, which decreased as tumours progressed (p

Background and aims
Quantifying systemic inflammation (SI) in acutely decompensated cirrhosis (ADC) is of major importance because SI is a driver of the most severe forms of ADC, including acute-on-chronic liver failure (ACLF). Blood biomarkers of SI already evaluated in ADC failed to appropriately assess SI in ADC. We aimed to investigate whether gene expression related to circulating immune cells could quantify SI in ADC.

Methods
Standard biomarkers (white cell count, C reactive protein, cytokines) and genome-wide RNA expression (RNA-sequencing) were obtained in blood from 700 patients with ADC at the time of their hospital admission. A composite score based on standard biomarkers of SI (Chronic Liver Failure-Standard Biomarkers Composite (CLIF-SBC) score) and a gene score (CLIF-Systemic Inflammation Gene (SIG) score) composed of the 28 top differentially expressed immune cell-related genes in the comparison between high-severity and low-severity clinical phenotypes were computed. Among the 700 patients, the CLIF-SIG score was repeated once during follow-up in 375 patients, and 3 times or more in 46 patients.

Results
The CLIF-SIG score was more accurate in reflecting clinical severity induced by SI than the CLIF-SBC score (area under the curve 0.803 vs 0.658). A CLIF-SIG score of 0.386 (Youden Index) was the best cut-off level discriminating patients with poor outcomes from the others, in all clinical scenarios. Sequential measurement of the CLIF-SIG score showed that 78% of patients were admitted at the peak or descending part of the SI-wave. ACLF developed during hospitalisation in 80% of patients with a CLIF-SIG score >0.386 on admission.

Conclusions
In patients with ADC, the CLIF-SIG score is an accurate estimator of SI, clinical course severity and prognosis.