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.
Search Results for: Diagnosi, trattamento e follow-up dei pazienti con vescica iperattiva
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Pronto soccorso terra di affanni: non solo per i milioni pazienti di ogni età e condizione di salute che rischiano di stazionarvi giorni e giorni – l’attesa media ufficiale è…
Incidence, progression and predictors of chronic kidney disease among adult HIV/AIDS patients on antiretroviral treatment in comprehensive specialised hospitals in the Amhara Region, Ethiopia, 2022: a multi-centre retrospective follow-up study
Objective
To assess the incidence, progression and predictors of chronic kidney disease among adult patients living with HIV/AIDS who are receiving antiretroviral therapy.
Design
An institution-based, multicentre retrospective follow-up study was conducted among a randomly selected sample of 535 adult patients. Data were entered into Epi Data version 4.6.0 and analysed using STATA version 14.0. A Cox proportional hazards regression model was fitted to identify independent predictors of chronic kidney disease incidence. Variables with p
Community-based rehabilitation approach in older adult population: a scoping review protocol
Introduction
The global population of individuals aged 60 years and older is growing rapidly, presenting multiple complex challenges, including frailty, cognitive decline, functional impairments, multimorbidity and polypharmacy. Consequently, addressing the rehabilitation needs of this age group poses significant difficulties in today’s world. There is some evidence that community-based rehabilitation approaches can meet the unique rehabilitation needs of older individuals. Therefore, this scoping review aims to explore the application of community-based rehabilitation approaches for the older adult population.
Methods and analysis
This scoping review will follow the methodological framework outlined by Arksey and O’Malley. The search will be conducted using academic databases, including PubMed, ScienceDirect, Embase, CINAHL and Web of Science, with the search terms ‘community-based rehabilitation,’ ‘aged,’ ‘older,’ ‘elder’ and ‘geriatric’. Additionally, Google Scholar will be used to identify relevant literature. Publications in English from inception to January 2025 that explicitly address community-based rehabilitation programmes for older adults will be eligible. Inclusion criteria encompass studies reporting on CBR interventions, outcomes or implementation targeting older adults with disabilities or vulnerabilities, across diverse geographic and socioeconomic contexts. Both peer-reviewed articles and grey literature (eg, reports, guidelines, theses) will be considered. Studies focusing solely on clinical or institutional rehabilitation without community components will be excluded. The study selection process will occur in two stages, involving the participation of three reviewers. A data extraction form will be used to systematically extract data from all included studies.
Ethics and dissemination
This scoping review was approved by the Ethics Committee of the University of Social Welfare and Rehabilitation Sciences (Code:IR.USWR.REC.1404.034), and the results will be published in a peer-reviewed scientific journal.
Understanding Predictors of Lifelong Initiation and Follow-up Treatment for adolescents and youth living with HIV (UPLIFT): an integrated prospective cohort in Eastern Cape, South Africa
Purpose
Adolescents living with HIV (ALHIV) are a priority population for achieving global HIV prevention and treatment targets but experience poorer outcomes than adults. Long-term follow-up is essential to understand their transition into adulthood. By linking self-reported survey data with routine laboratory records, we established a social science clinical cohort of ALHIV South Africa’s Eastern Cape to explore factors shaping their long-term health and well-being.
Participants
Eligible participants were adolescents who were part of a three-wave quantitative cohort of ALHIV and not living with HIV (2014–2018) and had consented (adolescent and caregiver) to having their self-reported interviews linked with routine health records (n=1563). Adolescents were recruited into the existing three-wave cohort through clinic and community-based methods (97% enrolment, >90% retention over three waves). Between 2019 and 2022, we abstracted laboratory test records from the National Health Laboratory Services database for all eligible participants, with matching based on demographic variables. Individuals with at least one HIV-related record form our ‘lifelong social science cohort’, a total of 956 ALHIV (852 of 1107 ALHIV and 104 of 456 HIV-uninfected).
Findings to date
A total of 32 886 laboratory test records from 2004 to 2023 were matched through three rounds of data extraction, using iteratively refined record-linking searches. Most records were viral load (8864) and CD4 count (6801) results, with a median of 10 (IQR: 7–14) and 8 (IQR: 5–11) tests per matched adolescent, respectively. Overall, 956 of 1563 adolescents (61%) were successfully linked to laboratory data, including 852 of 1107 (77%) ALHIV. Analysis of the matched cohort survey-laboratory data provided several insights. Self-reported antiretroviral therapy adherence was strongly associated with viral suppression, even after adjusting for covariates. The strongest predictors of suppression were not reporting missed doses in the past 3 days, past week and not missing clinic appointments in the past year. Among adolescent girls and young women living with HIV, access to safe and affordable facilities, and kind and respectful staff were associated with a higher likelihood of multiple improved HIV-related outcomes, including viral suppression. Exposure to sexual and intimate partner violence predicted worse viral load outcomes among adolescents.
Future plans
This integrated prospective cohort provides an opportunity to characterise long-term HIV treatment outcomes among ALHIV in Africa. We will investigate how individual, familial, community and healthcare experiences in childhood, and adolescence shape these outcomes. Since the COVID-19 pandemic happened during the period of matched data, we will also investigate the potential effect of the COVID-19 pandemic on adolescent HIV treatment outcomes, with potential subgroup analyses for individuals with available COVID-19-related results.
Brachial plexus nerve block versus haematoma block for closed reduction of distal radius fracture in adults: The BLOCK Trial – a protocol for a multicentre randomised controlled trial
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.
Psoriasi moderata-severa: bimekizumab permette una risposta clinica rapida e duratura [Dermatologia]
Al Congresso ICD 2025 sono stati presentati due studi che confermano l’efficacia duratura di bimekizumab nel trattamento della psoriasi a placche da moderata a severa, con risposte cliniche mantenute fino a quattro anni. I dati confermano inoltre tempi di risposta rapidi, con miglioramenti significativi già entro le prime settimane di trattamento.
Fattori di rischio per diabete nei pazienti con epatite C: il ruolo chiave del genotipo 3a e della cirrosi [Gastroenterologia ed epatologia]
Uno studio pubblicato su BMC Gastroenterology ha evidenziato che nei pazienti con epatite C cronica (CHC), genotipo 3a, età, cirrosi, ipertensione e insulino-resistenza e altri fattori indipendenti sono associati allo sviluppo di diabete di tipo 2 (T2DM). Interventi precoci nei pazienti a rischio possono migliorare la prognosi e ridurre le complicanze gravi.
Tumore del seno metastatico: Aifa approva elacestrant, dimezza il rischio di progressione [Oncologia-Ematologia]
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.
MSD si rafforza nelle patologie respiratorie e con $10 mld fa sua Verona Pharma [Business]
MSD ha annunciato l’acquisto di Verona Pharma per 10 miliardi di dollari. L’azienda ottiene così il controllo di Ohtuvayre (ensifentrina), un farmaco per il trattamento di mantenimento della broncopneumopatia cronica ostruttiva (BPCO). Il prezzo pattuito, 107 dollari per azione (american depositary shares), rappresenta un premio del 23% rispetto al prezzo di chiusura di martedì (86,86 dollari).
[Articles] Effects of empagliflozin on quality of life and healthcare use and costs in chronic kidney disease: a health economic analysis of the EMPA-KIDNEY trial
In EMPA-KIDNEY, 2 years treatment with empagliflozin improved QALYs, and reduced use and cost of other healthcare, resulting in high likelihood of cost-effectiveness across a broad range of patients with CKD. The study’s key limitation is its relatively short active treatment period and follow-up duration, which may lead to underestimation of the cost-effectiveness of long-term SGLT2i treatment in CKD.
Association Between Statin Use and Risk of Subarachnoid Hemorrhage: A Case-Control Study Using Large-Scale Claims Data
Stroke, Ahead of Print. BACKGROUND:While the efficacy of statins, which are cholesterol-lowering agents, in preventing subarachnoid hemorrhage (SAH) has been examined in experimental animal models and some clinical studies, findings remain inconclusive. This study aimed to investigate the association between statin use and the risk of SAH.METHODS:We conducted a large population-based case-control study using data from the Japanese Health Insurance Claims Database from January 2005 to August 2021. This nationwide database includes the data of individuals aged 0 to 74 years. Cases were defined as patients hospitalized with a first diagnosis of SAH (International Classification of Diseases, Tenth Revisioncode I60) during this period. Four controls per case were randomly selected and matched by age, sex, and follow-up period using incidence density sampling. Statin exposure (use, recency, and duration) was evaluated before the incidence of SAH. Conditional logistic regression, adjusted for patient characteristics, was used to assess the association between statin use and SAH risk. We also investigated whether this association varies with a history of hypertension, diabetes, cerebrovascular disease, unruptured intracranial aneurysms, and the use of antihypertensive medications.RESULTS:The study identified 3498 cases and 13 992 matched controls. Statin use was reported in 12.2% of SAH cases and 12.7% of the controls. After adjusting for patient characteristics, statin use was associated with a significantly reduced risk of SAH (adjusted odds ratio, 0.81 [95% CI, 0.69–0.95]). The association was significantly influenced by a history of hypertension or cerebrovascular disease (Pinteraction=0.042 and 0.042, respectively).CONCLUSIONS:Statin use was significantly associated with a reduced risk of SAH. These findings suggest that statins may play a role in the prevention of SAH, particularly in patients with a history of hypertension or cerebrovascular disease.
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Elenco dei centri specialistici della Regione Lazio, per la cura […]
Veneto
Elenco dei centri specialistici della Regione Veneto, per la cura […]
Basilicata
Elenco dei centri specialistici della Regione Basilicata, per la cura […]
Sicilia
Elenco dei centri specialistici della Regione Sicilia, per la cura […]