Clinical trials in Leber hereditary optic neuropathy: outcomes and opportunities.

Purpose Of Review: Leber hereditary optic neuropathy (LHON) is a mitochondrial DNA disease characterised by sequential bilateral vision loss due to loss of retinal ganglion cells. The purpose of this review is to provide an update on the results of recent clinical trials for LHON, focusing on studies of idebenone and lenadogene nolparvovec gene therapy.

Recent Findings: Evidence from three clinical studies (RHODOS, RHODOS-OFU, and LEROS) suggest that idebenone should be started early and continued for at least 24 months.

Systematic review of evidence for the impact and effectiveness of the 1-3-7 strategy for malaria elimination.

Background: The 1-3-7 approach to eliminate malaria was first implemented in China in 2012. It has since been expanded to multiple countries, but no systematic review has examined the evidence for its use. A systematic review was conducted aiming to evaluate the impact and effectiveness of the strategy and identify key challenges and variations in its implementation across different countries.

Left atrial appendage occlusion in patients with atrial fibrillation and intracerebral haemorrhage associated with cerebral amyloid angiopathy: a multicentre observational study and pooled analysis of published studies.

Background: Cerebral amyloid angiopathy (CAA) is a common cause of intracerebral haemorrhage (ICH) with a high recurrence risk. Left atrial appendage occlusion (LAAO) is a method for ischaemic stroke prevention in patients with atrial fibrillation (AF), potentially reducing the risk of intracranial bleeding in CAA-associated ICH. We aimed to determine the outcomes of patients with AF with CAA-associated ICH undergoing LAAO.

Clinical and Biomarker Determinants for Recurrent Stroke in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background And Objectives: Despite effective secondary prevention, including oral anticoagulant (OAC) therapy, the risk of recurrent stroke (RS) in patients with atrial fibrillation (AF) remains substantial with an annualized risk of 3.2%-6.5% per year.

Human papillomavirus vaccination for recalcitrant cutaneous warts.

•Recalcitrant warts affect immunocompetent and immunocompromised persons.•The optimal approach to refractory warts remains unclear.•Human papillomavirus vaccination is a promising therapy for recalcitrant warts.

Risk factors for benign uretero-enteric anastomotic strictures after open radical cystectomy and ileal conduit.

Introduction And Objective: Radical Cystectomy (RC) is one of the most common and complex surgical procedures in urologic surgery, and benign ureteroenteric anastomosis strictures (UAS) are complications described in about 15% of patients undergoing RC with different urinary diversion (UD). The aim of this study is to evaluate and analyze risk factors related to the development of ureteral stenosis after RC.

Materials And Methods: All consecutive patients who underwent RC with ileal conduit from December 2019 to December 2022 were included.

Novel insights into non-coding RNAs and their role in hydrocephalus.

A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation. This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus, one of the most common neurological conditions worldwide. In this review, we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition.

Metabolic targeting of neuroblastoma, an update.

Neuroblastoma is a paediatric cancer of the sympathetic nervous system that originates from the neural crest and can be categorised into stages and risk groups. Risk groups inform treatment options and high-risk cases bear a 50 % probability of relapse post-treatment remission. In neuroblastoma, MYCN amplification is the strongest predictor of unfavourable patient prognosis; circa 50 % of high-risk cases display MYCN amplification.

Comparative Efficacy and Safety of Endoscopic Modalities for Colorectal Cancer Screening in Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis.

Background & Aims: Long-standing inflammatory bowel disease (IBD) increases the risk of colonic neoplasia, necessitating effective screening strategies. This network meta-analysis compared the efficacy and safety between different endoscopic modalities in the high-definition (HD) era.

Methods: We searched CENTRAL, ClinicalTrials.

Frailty reduces penumbral volumes and attenuates treatment response in hyperacute ischemic stroke.

Background: Frailty-the loss of physiological reserve to withstand a stressor event-is associated with poorer outcomes following acute stroke reperfusion therapies. However, the mechanisms underlying this relationship are poorly understood. This study investigated the association between frailty and penumbral volumes in hyperacute ischemic stroke.

Smart control lipid-based nanocarriers for fine-tuning gut hormone secretion.

Modulating the endogenous stores of gastrointestinal hormones is considered a promising strategy to mimic gut endocrine function, improving metabolic dysfunction. Here, we exploit mouse and human knock-in and knockout intestinal organoids and show that agents used as commercial lipid excipients can activate nutrient-sensitive receptors on enteroendocrine cells (EECs) and, when formulated as lipid nanocarriers, can bestow biological effects through the release of GLP-1, GIP, and PYY from K and L cells. Studies in wild-type, dysglycemic, and gut knockout mice demonstrated that the effect exerted by lipid nanocarriers could be modulated by varying the excipients (e.

An update on immune-based alpha-synuclein trials in Parkinson's disease.

Parkinson's disease (PD) is a prevalent, chronic neurodegenerative disorder characterised by the progressive loss of dopaminergic neurons in the substantia nigra and other brain regions. The aggregation of alpha-synuclein (α-syn) into Lewy bodies and neurites is a key pathological feature associated with PD and its progression. Many therapeutic studies aim to target these aggregated forms of α-syn to potentially slow down or stop disease progression in PD.

Feasibility of embedding orthopaedic clinical trials into national registries: a pilot quality improvement study for the UK Non-Arthroplasty Hip Registry (UK-NAHR).

The integration of 'Registry-based Randomised Control Trials' (RRCT) into national registries has the potential to catalyse prospective research, enhancing the evidence base for practice. The aim of this study was to assess the feasibility of embedding a trial within the UK Non-Arthroplasty Hip Registry. This was a national observational, multi-centre study.

Relationship between the amplitudes of cerebral blood flow velocity and intracranial pressure using linear and non-linear approach.

Intracranial pressure (ICP), cerebral blood flow and volume are affected by craniospinal elasticity and cerebrospinal fluid dynamics, interacting in complex, nonlinear ways. Traumatic brain injury (TBI) may significantly alter this relationship. This retrospective study investigated the relationship between the vascular and parenchymal intracranial compartments by analysing two amplitudes: cerebral blood flow velocity (AmpCBFV) and ICP (AMP) during hypocapnia manoeuvre in TBI patients.

Knowing and not knowing: practical reflections on video based feedback as part of neuro-rehabilitation in a case of persistent anosognosia for hemiplegia.

We report the case of DT, a man in his fifties who suffered a large right fronto-parietal hemorrhage, resulting in a dense left weakness and a persistent anosognosia for the resultant hemiplegia. DT engaged in several video-feedback sessions. Video feedback therapy has been successful in previously reported cases of anosognosia, resulting in immediate and lasting resolution.

Chronic inorganic nitrate supplementation does not improve metabolic health and worsens disease progression in mice with diet-induced obesity.

Inorganic nitrate (NO) has been proposed to be of therapeutic use as a dietary supplement in obesity and related conditions including the metabolic syndrome (MetS), type II diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). Administration of NO to endothelial nitric oxide synthase-deficient mice reversed aspects of MetS; however, the impact of NO supplementation in diet-induced obesity is not well understood. Here we investigated the whole body metabolic phenotype and cardiac and hepatic metabolism in mice fed a high-fat, high-sucrose (HFHS) diet for up to 12 mo of age, supplemented with 1 mM NaNO (or NaCl) in their drinking water.

Association of Blood-Based Biomarkers and 6-Month Patient-Reported Outcomes in Patients With Mild TBI: A CENTER-TBI Analysis.

Background And Objectives: There is seemingly contradictory evidence concerning relationships between day-of-injury biomarkers and outcomes after mild traumatic brain injury (mTBI). To address this issue, we examined the association between a panel of biomarkers and multidimensional TBI outcomes.

Methods: Participants with mTBI (Glasgow coma scores [GCSs] 13-15) were selected from Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury, a European observational study recruiting patients with TBI with indication for brain CT and presentation within 24 hours.

Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 coactivation.

Initial clinical trials with drugs targeting epigenetic modulators - such as bromodomain and extraterminal protein (BET) inhibitors - demonstrate modest results in acute myeloid leukemia (AML). A major reason for this involves an increased transcriptional plasticity within AML, which allows cells to escape the therapeutic pressure. In this study, we investigated immediate epigenetic and transcriptional responses following BET inhibition and could demonstrate that BET inhibitor-mediated release of BRD4 from chromatin is accompanied by an acute compensatory feedback that attenuates down-regulation, or even increases expression, of specific transcriptional modules.

Predicting glioblastoma progression using MR diffusion tensor imaging: A systematic review.

Background And Purpose: Despite multimodal treatment of glioblastoma (GBM), recurrence beyond the initial tumor volume is inevitable. Moreover, conventional MRI has shortcomings that hinder the early detection of occult white matter tract infiltration by tumor, but diffusion tensor imaging (DTI) is a sensitive probe for assessing microstructural changes, facilitating the identification of progression before standard imaging. This sensitivity makes DTI a valuable tool for predicting recurrence.