Visualizing sarcomere and cellular dynamics in skeletal muscle to improve cell therapies.

The giant striated muscle protein titin integrates into the developing sarcomere to form a stable myofilament system that is extended as myocytes fuse. The logistics underlying myofilament assembly and disassembly have started to emerge with the possibility to follow labeled sarcomere components. Here, we generated the mCherry knock-in at titin's Z-disk to study skeletal muscle development and remodeling.

Cerebrospinal Fluid and Serum Neuron-Specific Enolase in Niemann-Pick Disease Type C1.

Niemann-Pick disease, type C1 (NPC1) is an ultra rare, autosomal recessive disorder characterized by impaired intracellular cholesterol trafficking. This study assessed neuron-specific enolase (NSE) as a biomarker for disease status and treatment response in individuals with NPC1. We also evaluated the concordance between serum and cerebrospinal fluid (CSF) NSE measurements.

Management of Postpartum Hemorrhage in Low- and Middle-Income Countries: Emergency Need for Updated Approach Due to Specific Circumstances, Resources, and Availabilities.

Postpartum hemorrhage (PPH) represents a critical emergency condition and the principal cause of maternal morbidity and mortality worldwide. It encompasses excessive bleeding following childbirth, which can arise from various causes. Prompt recognition and management are essential to mitigate severe outcomes and ensure maternal safety.

Linear Ablation Using a Contact Force-Sensing Catheter in Ablation for Persistent Atrial Fibrillation: A Prospective Randomized Trial.

: Pulmonary vein isolation (PVI) using radiofrequency catheter ablation with contact force (CF)-sensing technology has improved long-term outcomes in patients with atrial fibrillation. This prospective randomized study aimed to assess the efficacy and safety of CF-sensing technology for additional left atrial (LA) linear ablation of persistent AF (PerAF). : After PVI, anteromitral (AM) line and roof line ablation were performed using a CF-sensing catheter.

Conception and development of a neurological registry of patients with persistent health impairments following work-related COVID-19 disease in Germany.

Background: Healthcare and social workers had an increased occupational risk of contracting SARS-CoV-2 during the pandemic. Some developed long-lasting symptoms known as post-COVID syndrome (PCS). To assess the consequences of COVID-19 for individuals insured by the German Social Accident Insurance, the BG hospitals (Berufsgenossenschaftliche Kliniken: clinics for occupational accident insurance) established an interdisciplinary diagnostic programme.

Optimization of antiviral dosing in Herpesviridae encephalitis: a promising approach to improve outcome?

Background: Despite established antiviral therapy for herpes simplex virus, varicella zoster and cytomegalovirus encephalitis, the outcome remains poor.

Objectives: To assess pharmacokinetic (PK) and pharmacodynamic (PD) data of antiviral drugs in the central nervous system (CNS) to optimize the treatment of Herpesviridae encephalitis.

Sources: PUBMED search 1950 to September 2024, terms (1) "encephalitis" and ("HSV" or "VZV" or "CMV") or (2) cerebrospinal and ("(val)acyclovir" or "(val)ganciclovir" or "foscarnet" or "cidofovir").

Astrocyte Reactivity Polygenic Risk Score May Predict Cognitive Decline in Alzheimer's Disease.

Alzheimer's disease (AD) is a polygenic disorder with a prolonged prodromal phase, complicating early diagnosis. Recent research indicates that increased astrocyte reactivity is associated with a higher risk of pathogenic tau accumulation, particularly in amyloid-positive individuals. However, few clinical tools are available to predict which individuals are likely to exhibit elevated astrocyte activation and, consequently, be susceptible to hyperphosphorylated tau-induced neurodegeneration.

Myelin basic protein and TREM2 quantification in the CSF of patients with Multiple System Atrophy and other Parkinsonian conditions.

Background: It is well known that myelin disruption and neuroinflammation are early and distinct pathological hallmarks in multiple system atrophy (MSA) as well as in idiopathic Parkinson's disease and in other atypical Parkinsonian syndromes. The objective of this study was to assess the value of non-neuronal biomarker candidates that reflect myelin disruption and neuroinflammation.

Methods: Myelin basic protein (MBP) and the soluble form of TREM2 were quantified in a comprehensive movement disorder cohort from two different neurological centers, comprising a total of 171 CSF samples.

Multiple Central Nervous System Cryptococcomas Masquerading as Lymphoma.

Cryptococcal meningitis is a leading cause of morbidity and mortality in patients infected with human immunodeficiency virus. In over 90% of cases, it occurs at CD4 T lymphocyte (CD4) cell counts of less than 100 cells/mm. Cryptococcomas are rare granulomatous lesions that can occur in disseminated central nervous system cryptococcal infection, primarily in immunocompetent hosts.

Cefiderocol pharmacokinetics during acute pulmonary exacerbations in hospitalized adult persons with cystic fibrosis.

Persons with CF (pwCF) present altered pharmacokinetics (PK) and are often infected with multidrug-resistant (MDR) bacteria. Herein, we describe the PK of cefiderocol, a siderophore cephalosporin with potent activity against MDR Gram-negative rods, in hospitalized adult pwCF with acute pulmonary exacerbation (APE). PwCF received ≥3 doses of 2 g cefiderocol (3 h infusion) with frequency determined according to their estimated glomerular filtration rate (eGFR).

Leptomeningeal metastatic disease: new frontiers and future directions.

Leptomeningeal metastatic disease (LMD), encompassing entities of 'meningeal carcinomatosis', neoplastic meningitis' and 'leukaemic/lymphomatous meningitis', arises secondary to the metastatic dissemination of cancer cells from extracranial and certain intracranial malignancies into the leptomeninges and cerebrospinal fluid. The clinical burden of LMD has been increasing secondary to more sensitive diagnostics, aggressive local therapies for discrete brain metastases, and improved management of extracranial disease with targeted and immunotherapeutic agents, resulting in improved survival. However, owing to drug delivery challenges and the unique microenvironment of LMD, novel therapies against systemic disease have not yet translated into improved outcomes for these patients.

Development and validation of a liquid chromatography-tandem mass spectrometry assay for the simultaneous analysis of isoniazid and pyrazinamide in cerebrospinal fluid.

For the effective treatment of tuberculosis with first-line anti-tubercular drugs, drug concentrations need to be measured at the site of infection to determine drug exposure. To enable the measurement of the anti-tuberculosis drugs isoniazid and pyrazinamide in the nervous system of patients with tuberculous meningitis, an analytical method was developed and validated for the quantification of these drugs in human cerebrospinal fluid. Samples were prepared by solid phase extraction using Strata-X polymeric extraction plates.

Prevalence and associated factors of choroidal caverns in patients with type 2 diabetes mellitus.

Purpose: To study the prevalence of choroidal caverns (CCs) in patients with type 2 diabetes (T2DM) and their association with demographic and clinical data.

Methods: We included patients with T2DM and nondiabetic controls in a cross-sectional, monocenter study. The main outcome measure was the presence of CCs.

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.

A Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer.

Purpose: MET amplification (amp) is a driver of acquired resistance to epidermal growth factor receptor (EGFR) antibodies in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC). Savolitinib is an oral small molecule tyrosine kinase inhibitor that has demonstrated anti-tumor activity in MET-driven advanced solid tumors. We report the results of a phase 2 study of savolitinib in patients with mCRC with MET amp detected by circulating cell free (cf)DNA.

The heartbeat induces local volumetric compression in the healthy human brain: a 7 T magnetic resonance imaging study on brain tissue pulsations.

Intracerebral blood volume changes along the cardiac cycle cause volumetric strain in brain tissue, measurable with displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging. Individual volumetric strain maps show compressing and expanding voxels, raising the question whether systolic compressions reflect a physiological phenomenon. In DENSE data from nine healthy volunteers, voxels were grouped into three clusters according to volumetric strain in a tissue mask excluding extracerebral blood vessels and cerebrospinal fluid using a two-stage clustering approach.

Treatment effects of elexacaftor/tezacaftor/ivacaftor on people with cystic fibrosis heterozygous for 3849+10kbC->T and a class I variant.

Background: The splice variant 3849+10kbC->T (c.3717+12191C>T) (3849 variant) is a residual function CFTR variant, characterized by insertion of an in-frame stop codon into most CFTR transcripts. Both ivacaftor (Iva) and tezacaftor/ivacaftor (Tez/Iva) have been approved for people with CF (pwCF) carrying the 3849 variant.

Revisiting the Endoscopic Third Ventriculostomy Success Score using machine learning: can we do better?

Objective: The Endoscopic Third Ventriculostomy Success Score (ETVSS) is a useful decision-making heuristic when considering the probability of surgical success, defined traditionally as no repeat cerebrospinal fluid diversion surgery needed within 6 months. Nonetheless, the performance of the logistic regression (LR) model in the original 2009 study was modest, with an area under the receiver operating characteristic curve (AUROC) of 0.68.

Transcranial penetrating skull base trauma with metal rod: Endoscopic repair of CSF leak.

Background: Penetrating skull base injuries are complex clinical scenarios requiring multidisciplinary management to address both immediate life-threatening conditions and long-term complications.Anterior skull base fractures account for 21% of skull fractures from which 4% were caused by head trauma [1]. Post-traumatic cerebrospinal fluid (CSF) leaks may arise, becoming a major source of morbidity; these can lead to the development of severe intracranial infections [2].

ACT with CF: A randomized trial of acceptance and commitment therapy vs supportive psychotherapy for adults with cystic fibrosis.

Purpose: Psychological distress, including anxiety and depression, is common among adults with CF, associating with poor quality of life, lung function, and healthcare utilization. This 3-year, multi-site, telehealth-delivered randomized trial sought to determine whether Acceptance and Commitment Therapy (ACT with CF) is superior to supportive psychotherapy (SP), in improving psychological functioning for adults with CF.

Methods: One hundred twenty-four adults with CF and elevated anxiety and/or depressive symptoms were recruited coincident with the first COVID lockdown, from Thomas Jefferson University Hospitals, University of Virginia, Augusta University, Duke University Medical Center, and social media.

Expanding the Impact of New Cystic Fibrosis Therapies in Low- and Middle-Income Countries.

Background: Cystic fibrosis (CF) primarily affects Caucasian populations, with the highest prevalence in countries like Ireland, the UK, Australia, and Canada. Despite significant improvements in survival, pulmonary insufficiency remains the leading cause of death. Factors such as nutrition, chronic Pseudomonas aeruginosa (PsA) infection, genotype, pancreatic status, and cystic fibrosis-related diabetes affect pulmonary function across age groups.

Viral Polymerase Chain Reaction Testing of the Cerebrospinal Fluid: Comprehensive Care for Neonates With a Fever.

Neonates who develop fever have a high risk for serious infection, and while the standard of care involves performing a full sepsis evaluation, current guidelines do not include viral polymerase chain reaction (PCR) testing of the cerebrospinal fluid as a standard of care, which means that cases of viral meningitis can be missed. This case presentation discusses a neonate who had a fever at four days of life who then underwent a full sepsis evaluation. A respiratory viral panel demonstrated rhino/enterovirus positivity.