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Category: biotech/medical

Early Rule Out With a Refreshed Troponin Assay

💬 Editorial: A sixth-generation high-sensitivity cardiac troponin T assay could allow clinicians to reassure more emergency department patients they are not having a myocardial infarction at presentation, but further study is needed to optimize clinical application.

In 2008, Roche Diagnostics introduced a high-sensitivity version of their cardiac troponin T assay (hs-cTnT), a fifth-generation assay. Researchers quickly deduced that by using the assay’s limit of detection (LoD) of 5 ng/L (to convert to micrograms per liter, multiply by 0.001) as a cutoff, many patients could safely be classified as very low-risk for myocardial infarction (MI).1,2 Researchers gathered data across multiple institutions, and a 9241-patient meta-analysis demonstrated a pooled sensitivity for the LoD of 98.7%.3 Outside the US, on presentation (0-hour) concentrations less than LoD became guideline recommended, reassuring patients quickly and reducing time spent in busy emergency departments (EDs). Once US Food and Drug Administration (FDA) approval was obtained in the US, a similar risk-stratification approach became possible, though using a threshold of 6 ng/L because the FDA mandated that exact concentrations below the limit of quantitation (LoQ) be not reported. In the meantime, troponin I assay manufacturers brought to market high-sensitivity cardiac troponin I (hs-cTnI) assays. Low-risk thresholds were derived for these that were above the LoD and LoQ by identifying the concentration that gave a minimum prespecified statistical performance. Most often these minimums are greater than or equal to 99% sensitivity4 and greater than or equal to 99.5% negative predictive value (NPV). Roche Diagnostics has now placed in the hands of researchers a sixth-generation cTnT assay. Already this has been established as high sensitivity, with very low LoD and LoQ and well-defined sex-specific upper-reference levels.5 This will allow, for the first time with hs-cTnT, the derivation of single-sample, very low-risk thresholds likely usable across institutions. In this issue of JAMA Cardiol ogy, Thurston and colleagues6 present the first such derivation of a single-sample, very low-risk threshold for the Roche sixth-generation hs-cTnT assay.

In a prospective cohort study of 987 patients, blood was drawn at multiple time points from ED presentation. cTnT concentrations were measured on the same analyzer with both the fifth-and sixth-generation assays. This allowed derivation of a sixth-generation single-sample very low-risk threshold, a comparison of the performance of that threshold with the fifth-generation LoD, and determination of the performance of the High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome (High-STEACS) early rule-out pathway. External validation used stored samples from the Advantageous Predictors of Acute Coronary Events (APACE) study. The primary outcome was an index or subsequent MI (types 1, 4b, or 4c) or cardiac death within 30 days. The prespecified goal was to determine the highest troponin threshold with statistical metrics NPV greater than or equal to 99.5% and sensitivity greater than or equal to 99%.

Pallidus internus versus subthalamic nucleus deep brain stimulation for Meige syndrome: a randomized, controlled, double-blind multicenter trial

The aim of this randomized, controlled, double-blind multicenter trial was to compare the safety and efficacy of globus pallidus internus (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Meige syndrome (MeS). Additionally, the authors explored the optimal site of DBS and identified predictors of clinical outcomes.

The primary outcome was improvement in motor function as assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The secondary outcomes included mood, global cognitive function, and quality of life (QOL). The optimal stimulation site for DBS was investigated using Lead-DBS.

A total of 62 patients with MeS were randomized to receive GPi-DBS (n = 31) or STN-DBS (n = 31), and all completed the 1-year follow-up. In the GPi-DBS group, the mean improvement rates in BFMDRS movement scores were 54.9%, 57.3%, and 59.7% at 3, 6, and 12 months, respectively. In the STN-DBS group, the corresponding rates were 57.1%, 59.0%, and 59.9%. There was no significant difference in the efficacy of motor symptoms, depression, anxiety, and QOL between the two groups during follow-up. The total electrical energy delivered in the GPi-DBS group was significantly greater than that in the STN-DBS group. The adverse event rates were comparable between the GPi-DBS (16.1%) and STN-DBS (12.9%) groups (p 0.99). The “sweet spot” for GPi-DBS was found to be located in the posterolateral dorsal pallidum (ρ = 0.76, p = 0.001), while the sweet spot for STN-DBS was found to be situated in the dorsal subthalamic nucleus (ρ = 0.66, p = 0.005).

Bayesian probabilistic density mapping of the decussating dentato-rubro-thalamic tract to predict clinical tremor improvement in MRgFUS

OBJECTIVE Magnetic resonance–guided focused ultrasound (MRgFUS) is increasingly recognized as an effective treatment option for patients with medication-refractory essential tremor (ET). Indirect coordinates of the ventral intermediate nucleus of the thalamus, as well as the dentato-rubro-thalamic tract (DRTT) originating from the ipsilateral dentate nucleus, known as the “nondecussating DRTT” (nd-DRTT), are commonly used as targets for sonication. Anatomically, the DRTT originating from the contralateral dentate nucleus, referred to as the “decussating DRTT” (d-DRTT), constitutes the predominant component of the two fiber populations. However, the d-DRTT is rarely visualized using conventional diffusion tensor imaging (DTI) because of the technical challenges associated with resolving crossing fiber orientations. Probabilistic tractography enables the differentiation of crossing fibers, thus allowing for visualization of both the d-DRTT and nd-DRTT. Authors of this study aimed to evaluate whether the d-DRTT delineated by probabilistic tractography represents an anatomical target more important than indirect coordinates or the nd-DRTT. METHODS Consecutive patients with medically refractory ET who underwent unilateral MRgFUS thalamotomy at a single institution between May 2022 and August 2024 were analyzed. Tremor severity was assessed using the Clinical Rating Scale for Tremor Part B, and the percentage improvement at 3 months after treatment was calculated as an indicator of functional recovery. Probabilistic tractography of the DRTT was performed post hoc using preoperative diffusion MRI and Bayesian modeling (BedpostX) and probabilistic tracking (ProbtrackX). The distances between the sonicated lesion as detected on postoperative MRI and each of the following were compared: indirect coordinates, nd-DRTT, and d-DRTT. Subgroup analysis was performed on patients with a peak lesion temperature ≄ 55°C. Pearson correlation was used to assess the relationships between distance metrics and clinical outcomes. RESULTS Probabilistic tractography successfully visualized the d-DRTT in all 28 patients included in the study. The d-DRTT was more lateral than both the indirect coordinate and the nd-DRTT (p < 0.01 for both), with a nonsignificant tendency for a more anterior position relative to the nd-DRTT (p = 0.054). Among the patients with a peak lesion temperature ≄ 55°C, the distance between the sonicated lesion and the d-DRTT showed a strong correlation with clinical outcomes, whereas that between the lesion and nd-DRTT showed a moderate correlation; the indirect coordinates showed no significant correlation. CONCLUSIONS Probabilistic tractography successfully visualized the d-DRTT, and its location appears to capture the “tremor-relevant” neural pathway more accurately than either the indirect coordinate or the nd-DRTT.

Efficacy and Safety of VMAT2 Inhibitors in the Treatment of Huntington DiseaseA Meta-Analysis of Randomized Clinical Trials

In patients with Huntington disease, vesicular monoamine transporter 2 inhibitors (VMAT2is) treatment improved chorea without significant changes in adverse effects or depressive symptoms.

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Hidden mosquito viruses emerge as RNA immune signals map global infections

Aedes aegypti, commonly known as the yellow fever mosquito, is a highly adapted, invasive mosquito species recognized as a major global health threat that acts as the primary vector for several severe diseases, most notably dengue fever, as well as yellow fever, chikungunya and Zika virus. Local government agencies conduct routine molecular surveillance of these mosquitoes to detect and track viruses. However, they are primarily limited to using conventional reverse transcription polymerase chain reaction methodologies, which can only detect known pathogens that have already been identified and for which specific genetic primers have been developed.

Recent research efforts applying high-throughput RNA sequencing have led to a large expansion in the mosquito virome (the entire collection of viruses contained within mosquitoes). However, questions remain as to how persistent insect viruses are within mosquito colonies, how insect viruses interact with mosquito immune responses and how frequently insect viruses can be transmitted.

A new study by Boston University Chobanian & Avedisian School of Medicine researchers looked at the mosquitoes’ immune response to discover many more insect viruses and they hope to someday use the mosquitoes’ own immune system to battle some of the most pervasive and antagonistic human viruses. The findings are published in the journal Nature Communications.

Alzheimer’s Drug Review Ignites Backlash From Experts

A systematic review suggested that drugs targeting amyloid beta appeared to have no clinically meaningful positive effects, sparking swift backlash from Alzheimer’s disease experts.

— Study under fire for mixing data on failed and new anti-amyloid therapies to draw conclusions.

Abstract: Proposing a no-nonsense strategy for the treatment of dominant neurodevelopmental disorders:

Xiaochang Zhang & team introduce exon annotation for nonsense-mediated mRNA (EANMD) and report on alternatively spliced exons in the brain that trigger mRNA decay, noting modulation of such exons in disease-causal genes can potentially treat neurodevelopmental disorders.

Address correspondence to: Xiaochang Zhang, University of Chicago, Cummings Life Science Center 507A, 920 E. 58th St., Chicago, Illinois 60,637, USA. Phone: 773.834.5369; Email: [email protected].

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