The state-of-the-art of N-of-1 therapies and the IRDiRC N-of-1 development roadmap.

In recent years, a small number of people with rare diseases caused by unique genetic variants have been treated with therapies developed specifically for them. This pioneering field of genetic N-of-1 therapies is evolving rapidly, giving hope for the individualized treatment of people living with very rare diseases. In this Review, we outline the concept of N-of-1 individualized therapies, focusing on genetic therapies, and illustrate advances and challenges in the field using cases for which therapies have been successfully developed.

Transforaminal Endoscopic Lumbar Discectomy versus Coblation Nucleoplasty Combined with Collagenase Chemonucleolysis for Lumbar Disc Herniation with Grade I Degenerative Spondylolisthesis.

Introduction: To investigate the short-term clinical effect of transforaminal endoscopic lumbar discectomy (TELD) versus coblation nucleoplasty (CN) combined with collagenase chemonucleolysis (CCNL) in the treatment of lumbar disc herniation (LDH) with grade I degenerative spondylolisthesis.

Methods: From January 2019 to December 2020, 60 patients who had LDH with grade I degenerative spondylolisthesis were divided into two groups. Group A adopted TELD while Group B adopted CN combined with CCNL.

Serum neurofilament light and glial fibrillary acidic protein levels are not associated with wearing-off symptoms in natalizumab-treated multiple sclerosis patients.

Background: Biomarkers of neuronal and axonal damage (serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP)) may provide insight into the aetiology of natalizumab wearing-off symptoms (WoSs).

Objectives: We investigated the longitudinal association between and predictive value of sNfL and sGFAP and the occurrence of WoS in MS patients treated with natalizumab.

Methods: We performed longitudinal measurements of sNfL and sGFAP in NEXT-MS trial participants who completed a questionnaire about WoS.

EUS-guided gastroenterostomy for malignant gastric outlet obstruction: impact of clinical and demographic factors on outcomes.

Background And Aims: EUS-guided gastroenterostomy (EUS-GE) has emerged as an alternative to surgical gastrojejunostomy and endoluminal stenting for malignant gastric outlet obstruction (MGOO). Studies regarding factors associated with the EUS-GE outcomes are limited.

Methods: A retrospective observational study was conducted with consecutive patients who underwent EUS-GE for MGOO from January 2016 to November 2023.

Hypothalamic Hyperphagia in the Hospice Patient: Case Report and Discussion.

We present a case of insatiable appetite and harmful overeating in a hospice patient that showcases the burden of hypothalamic hyperphagia, a rare complication of brain cancer. While confounders exist such as progression of disease and prior tapering of dexamethasone, in this case the initiation of metformin was associated with substantial appetite reduction and resolution of our patient's debilitating food-seeking behaviors. We will explore metformin as a potential cost-effective option for palliation in a hospice setting and explore some of the physiologic mechanisms involved.

Prophylactic Antibiotics in Adults With Acute Brain Injury Who Are Invasively Ventilated in the ICU: A Systematic Review and Meta-Analysis.

Background: Lower respiratory tract infections are common in patients receiving invasive mechanical ventilation in an ICU after an acute brain injury and may have deleterious consequences.

Research Question: In adults with acute brain injury receiving invasive mechanical ventilation in an ICU, is the administration of prophylactic parenteral antibiotics, compared with placebo or usual care, associated with reduced mortality?

Study Design And Methods: We conducted a systematic review and meta-analysis. We searched for randomized clinical trials (RCTs) in electronic databases, as well as unpublished trials.

Bias and precision of SPECT-based Lu activity-concentration estimation using a ring-configured solid-state versus a dual-headed anger system.

Background: The aim was to compare bias and precision for Lu-SPECT activity-concentration estimation using a dual-headed Anger SPECT system and a ring-configured CZT SPECT system. This was investigated for imaging at 208 keV and 113 keV, respectively.

Methods: Phantom experiments were performed on a GE Discovery 670 system with 5/8'' NaI(Tl) crystal (dual-headed Anger system) and a GE StarGuide (ring-configured CZT system).

Epoxytiglianes induce keratinocyte wound healing responses via classical protein kinase C activation to promote skin re-epithelialization.

Epoxytiglianes are a novel class of diterpene esters. The prototype epoxytigliane, EBC-46 (tigilanol tiglate), is a potent anti-cancer agent in clinical development for local treatment of a range of human and animal tumors. EBC-46 also consistently promotes wound re-epithelialization at the treatment sites, mediated via activation of classical protein kinase C (PKC) isoforms.

A scenario for an evolutionary selection of ageing.

Signs of ageing become apparent only late in life, after organismal development is finalized. Ageing, most notably, decreases an individual's fitness. As such, it is most commonly perceived as a non-adaptive force of evolution and considered a by-product of natural selection.

Xe Image Processing Pipeline: An open-source, graphical user interface application for the analysis of hyperpolarized Xe MRI.

Purpose: Hyperpolarized Xe MRI presents opportunities to assess regional pulmonary microstructure and function. Ongoing advancements in hardware, sequences, and image processing have helped it become increasingly adopted for both research and clinical use. As the number of applications and users increase, standardization becomes crucial.

Synergistic effect of folic acid and hypericin administration to improve the efficacy of photodynamic therapy via folate receptors.

Transport systems are developed to improve the solubility of the transported drug, increase its stability, enhance its pharmacological activity and target cancer while minimising side effects. In this work, nanoporous silica particles that can be functionalized and loaded with a large number of hydrophobic molecules are proposed. The designed system was modified with folic acid to target the folic acid receptors of cancer cells.

Interleukin-6, C-Reactive Protein, and Recurrence After Stroke: A Time-Course Analysis of Individual-Participant Data.

Background: Inflammation promotes atherogenesis. Randomized controlled trials of anti-inflammatory therapies for prevention after stroke have not yet demonstrated clear benefit. IL-6 (interleukin-6) and hsCRP (high-sensitivity C-reactive protein) are independently associated with major adverse cardiovascular events poststroke and may guide patient selection in future randomized controlled trials.

A retrospective audit of an artificial intelligence software for the detection of intracranial haemorrhage used by a teleradiology company in the United Kingdom.

Objectives: Artificial intelligence (AI) algorithms have the potential to assist radiologists in the reporting of head computed tomography (CT) scans. We investigated the performance of an AI-based software device used in a large teleradiology practice for intracranial haemorrhage (ICH) detection.

Methods: A randomly selected subset of all non-contrast CT head (NCCTH) scans from patients aged ≥18 years referred for urgent teleradiology reporting from 44 different hospitals within the United Kingdom over a 4-month period was considered for this evaluation.

Association between Exposure to Metals during Pregnancy, Childhood Gut Microbiome, and Risk of Intestinal Inflammation in Late Childhood.

Alterations to the gut microbiome and exposure to metals during pregnancy have been suggested to impact inflammatory bowel disease. Nonetheless, how prenatal exposure to metals eventually results in long-term effects on the gut microbiome, leading to subclinical intestinal inflammation, particularly during late childhood, has not been studied. It is also unknown whether such an interactive effect drives a specific subgroup of children toward elevated susceptibility to intestinal inflammation.

Consequences of Legal Infractions on the General Surgery Residency Application Process.

Objective: Alcohol and drug-related legal infractions are common among college and medical students. The objective of this work is to quantify the influence of these legal infractions on program directors (PDs) when making decisions on applicants to general surgery residencies.

Design: A convenience sample of 72 PDs with publicly accessible email addresses were electronically sent a previously piloted survey tool.

Value of projectional imaging relative to cross-sectional imaging to assess catheter tip position in the superior vena cava: evaluation of reader variability.

Objectives: The cavo-atrial junction (CAJ) is the most appropriate central venous catheters CVC tip location to reduce complications. Among chest X-ray (CXR) landmarks for tips assessment, only the pericardial reflection lies in the same plane as the vascular structures. We aimed to evaluate the observer variability to determine tip positioning on CXR, using CT as a gold standard.

Impacts of Hospital Volume and Patient-Hospital Distances on Outcomes of Older Adults Receiving Percutaneous Microaxial Ventricular Assist Devices for Cardiogenic Shock.

Background: Percutaneous microaxial ventricular assist devices (pVADs) have the potential to reduce mortality of patients with cardiogenic shock (CS). However, the association between the distribution of pVAD-performing centers and outcomes of CS has not been explored.

Methods: This observational study included Medicare fee-for-service beneficiaries aged 65 to 99 years treated with pVAD for CS from 2016 to 2020.